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The Bone & Joint Journal
Vol. 97-B, Issue 8 | Pages 1106 - 1110
1 Aug 2015
Kherad M Mellström D Rosengren BE Hasserius R Nilsson J Redlund-Johnell I Ohlsson C Lorentzon M Karlsson MK

We sought to determine whether specific characteristics of vertebral fractures in elderly men are associated with low bone mineral density (BMD) and osteoporosis. . Mister osteoporosis Sweden is a population based cohort study involving 3014 men aged 69 to 81 years. Of these, 1427 had readable lateral radiographs of the thoracic and lumbar spine. Total body (TB) BMD (g/cm²) and total right hip (TH) BMD were measured by dual energy x-ray absorptiometry. The proportion of men with osteoporosis was calculated from TH BMD. There were 215 men (15.1%) with a vertebral fracture. Those with a fracture had lower TB BMD than those without (p < 0.001). Among men with a fracture, TB BMD was lower in those with more than three fractures (p = 0.02), those with biconcave fractures (p = 0.02) and those with vertebral body compression of > 42% (worst quartile) (p = 0.03). The mean odds ratio (OR) for having osteoporosis when having any type of vertebral fracture was 6.1 (95% confidence interval (CI) 3.9 to 9.5) compared with those without a fracture. A combination of more than three fractures and compression in the worst quartile had a mean OR of 114.2 (95% CI 6.7 to 1938.3) of having osteoporosis compared with those without a fracture. . We recommend BMD studies to be undertaken in these subcohorts of elderly men with a vertebral fracture. Cite this article: 2015;97-B:1106–10


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Methods

We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).


Bone & Joint Research
Vol. 11, Issue 12 | Pages 873 - 880
1 Dec 2022
Watanabe N Miyatake K Takada R Ogawa T Amano Y Jinno T Koga H Yoshii T Okawa A

Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the reduction of the postoperative revision rate after THA. Cite this article: Bone Joint Res 2022;11(12):873–880


Bone & Joint Research
Vol. 12, Issue 9 | Pages 590 - 597
20 Sep 2023
Uemura K Otake Y Takashima K Hamada H Imagama T Takao M Sakai T Sato Y Okada S Sugano N

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597


Bone & Joint Research
Vol. 11, Issue 5 | Pages 304 - 316
17 May 2022
Kim MH Choi LY Chung JY Kim E Yang WM

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 254 - 260
1 Mar 2023
Bukowski BR Sandhu KP Bernatz JT Pickhardt PJ Binkley N Anderson PA Illgen R

Aims. Osteoporosis can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation. Methods. Retrospective chart review of a single-surgeon database identified 78 patients with CTXA performed prior to robotic-assisted THA (raTHA) (Group 1). Group 1 was age- and sex-matched to 78 raTHAs that had a preoperative hip CT but did not have CTXA analysis (Group 2). Clinical demographics, femoral fixation method, CTXA, and DXA data were recorded. Demographic data were similar for both groups. Results. Preoperative femoral BMD was available for 100% of Group 1 patients (CTXA) and 43.6% of Group 2 patients (DXA). CTXA analysis for all Group 1 patients preoperatively identified 13 osteopenic and eight osteoporotic patients for whom there were no available preoperative DXA data. Cemented stem fixation was used with higher frequency in Group 1 versus Group 2 (28.2% vs 14.3%, respectively; p = 0.030), and in all cases where osteoporosis was diagnosed, irrespective of technique (DXA or CTXA). Conclusion. Preoperative hip CT scans which are routinely obtained prior to raTHA can determine bone health, and thus guide femoral fixation strategy. Systematic preoperative evaluation with CTXA resulted in increased recognition of osteopenia and osteoporosis, and contributed to increased use of cemented femoral fixation compared with routine clinical care; in this small study, however, it did not impact short-term periprosthetic fracture risk. Cite this article: Bone Joint J 2023;105-B(3):254–260


Bone & Joint Research
Vol. 11, Issue 4 | Pages 200 - 209
1 Apr 2022
Liu YD Liu JF Liu B

Aims. The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development. Methods. Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot. Results. The established diabetic mice were more sensitive to ovariectomy (OVX)-induced osteoporosis, and DMF treatment inhibited the sensitivity. OVX-treated diabetic mice exhibited higher TRAP5b and c-terminal telopeptides of type 1 (CTX1) levels, and DMF treatment inhibited the enhancement. DMF reduced RAW 264.7 cell viability. Glucose treatment enhanced the levels of TRAP5b, cathepsin K, Atp6v0d2, and H. +. -ATPase, ROS, while DMF reversed this phenotype. The glucose-increased protein levels were inhibited by DMF in cells treated with RANKL. The expression levels of antioxidant enzymes Gclc, Gclm, Ho-1, and Nqo1 were upregulated by DMF. DMF attenuated high glucose-caused osteoclast differentiation by targeting mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in BMMs. Conclusion. DMF inhibits high glucose-induced osteoporosis by targeting MAPK and NF-κB signalling. Cite this article: Bone Joint Res 2022;11(4):200–209


Bone & Joint Research
Vol. 6, Issue 12 | Pages 640 - 648
1 Dec 2017
Xia B Li Y Zhou J Tian B Feng L

Objectives. Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Methods. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs. Results. A total of 1320 DEGs were obtained, of which 855 were up-regulated and 465 were down-regulated. These differentially expressed genes were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, mainly associated with gene expression and osteoclast differentiation. In the transcriptional regulatory network, there were 6038 interactions pairs involving 88 transcriptional factors. In addition, the quantitative reverse transcriptase-polymerase chain reaction result validated the expression of several genes (VPS35, FCGR2A, TBCA, HIRA, TYROBP, and JUND). Finally, ROC analyses showed that VPS35, HIRA, PHF20 and NFKB2 had a significant diagnostic value for osteoporosis. Conclusion. Genes such as VPS35, FCGR2A, TBCA, HIRA, TYROBP, JUND, PHF20, NFKB2, RPL35A and BICD2 may be considered to be potential pathogenic genes of osteoporosis and may be useful for further study of the mechanisms underlying osteoporosis. Cite this article: B. Xia, Y. Li, J. Zhou, B. Tian, L. Feng. Identification of potential pathogenic genes associated with osteoporosis. Bone Joint Res 2017;6:640–648. DOI: 10.1302/2046-3758.612.BJR-2017-0102.R1


Bone & Joint Research
Vol. 12, Issue 6 | Pages 375 - 386
12 Jun 2023
Li Z

Aims. Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP. Methods. Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p. Results. The expression of PCBP1-AS1 was pre-eminent in OP tissues and decreased throughout the development of human bone marrow-derived mesenchymal stem cells (hBMSCs) into osteoblasts. PCBP1-AS1 knockdown and overexpression respectively promoted and suppressed hBMSC proliferation and osteogenic differentiation capacity. Mechanistically, PCBP1-AS1 sponged miR-126-5p and consequently targeted PAK2. Inhibiting miR-126-5p significantly counteracted the beneficial effects of PCBP1-AS1 or PAK2 knockdown on hBMSCs’ ability to differentiate into osteoblasts. Conclusion. PCBP1-AS1 is responsible for the development of OP and promotes its progression by inducing PAK2 expression via competitively binding to miR-126-5p. PCBP1-AS1 may therefore be a new therapeutic target for OP patients. Cite this article: Bone Joint Res 2023;12(6):375–386


Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment. Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1


Bone & Joint Research
Vol. 7, Issue 4 | Pages 289 - 297
1 Apr 2018
Sanghani-Kerai A Osagie-Clouard L Blunn G Coathup M

Objectives. This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. Results. CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). Conclusion. Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats. Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1272 - 1274
1 Sep 2005
El Masry MA Saha A Calder SJ

Transient osteoporosis is an uncommon, self-limiting, reversible condition. We report a case involving the knee following trauma. The aetiology is unknown, but the association between transient osteoporosis and trauma has not been documented previously. The clinical presentation represents a degree of overlap among various clinical syndromes, including reflex sympathetic dystrophy and avascular necrosis. The diagnosis was confirmed by bone scan and MRI. The patient, a 47-year-old man, was treated with non-steroidal anti-inflammatory medication, protected weight-bearing and physiotherapy. He made a full clinical recovery and bone quality returned to virtual normality


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65


Bone & Joint Research
Vol. 11, Issue 11 | Pages 763 - 776
1 Nov 2022
Zhang Y Jiang B Zhang P Chiu SK Lee MH

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776


Bone & Joint Open
Vol. 5, Issue 6 | Pages 457 - 463
2 Jun 2024
Coviello M Abate A Maccagnano G Ippolito F Nappi V Abbaticchio AM Caiaffa E Caiaffa V

Aims. Proximal femur fractures treatment can involve anterograde nailing with a single or double cephalic screw. An undesirable failure for this fixation is screw cut-out. In a single-screw nail, a tip-apex distance (TAD) greater than 25 mm has been associated with an increased risk of cut-out. The aim of the study was to examine the role of TAD as a risk factor in a cephalic double-screw nail. Methods. A retrospective study was conducted on 112 patients treated for intertrochanteric femur fracture with a double proximal screw nail (Endovis BA2; EBA2) from January to September 2021. The analyzed variables were age, sex, BMI, comorbidities, fracture type, side, time of surgery, quality of reduction, pre-existing therapy with bisphosphonate for osteoporosis, screw placement in two different views, and TAD. The last follow-up was at 12 months. Logistic regression was used to study the potential factors of screw cut-out, and receiver operating characteristic curve to identify the threshold value. Results. A total of 98 of the 112 patients met the inclusion criteria. Overall, 65 patients were female (66.3%), the mean age was 83.23 years (SD 7.07), and the mean follow-up was 378 days (SD 36). Cut-out was observed in five patients (5.10%). The variables identified by univariate analysis with p < 0.05 were included in the multivariate logistic regression model were screw placement and TAD. The TAD was significant with an odds ratio (OR) 5.03 (p = 0.012) as the screw placement with an OR 4.35 (p = 0.043) in the anteroposterior view, and OR 10.61 (p = 0.037) in the lateral view. The TAD threshold value identified was 29.50 mm. Conclusion. Our study confirmed the risk factors for cut-out in the double-screw nail are comparable to those in the single screw. We found a TAD value of 29.50 mm to be associated with a risk of cut-out in double-screw nails, when good fracture reduction is granted. This value is higher than the one reported with single-screw nails. Therefore, we suggest the role of TAD should be reconsidered in well-reduced fractures treated with double-screw intramedullary nail. Cite this article: Bone Jt Open 2024;5(6):457–463


Bone & Joint Research
Vol. 12, Issue 7 | Pages 423 - 432
6 Jul 2023
Xie H Wang N He H Yang Z Wu J Yang T Wang Y

Aims. Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture). Methods. PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health. Results. From 748 non-duplicate publications, 19 studies were included. We found a significantly positive association between dietary selenium intake (β = 0.04, 95% confidence interval (CI) 0.00 to 0.07, p = 0.029) as well as serum selenium (β = 0.13, 95% CI 0.00 to 0.26, p = 0.046) and BMD. Consistently, those with higher selenium intake had a lower risk of OP (OR = 0.47, 95% CI 0.31 to 0.72, p = 0.001), and patients with OP had a significantly lower level of serum selenium than healthy controls (WMD = -2.01, 95% CI -3.91 to -0.12, p = 0.037). High dietary selenium intake was associated with a lower risk of hip fracture (OR = 0.44, 95% CI 0.37 to 0.52, p < 0.001). Conclusion. Selenium was positively associated with BMD and inversely associated with OP; dietary selenium intake was negatively associated with hip fracture. The causality and therapeutic effect of selenium on OP needs to be investigated in future studies. Cite this article: Bone Joint Res 2023;12(7):423–432


Bone & Joint Open
Vol. 4, Issue 7 | Pages 507 - 515
6 Jul 2023
Jørgensen PB Jakobsen SS Vainorius D Homilius M Hansen TB Stilling M

Aims. The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems. Methods. In this case-control study, 25 patients (22 female) at mean age of 78 years (70 to 89) received cemented Exeter short stem (case group). Cases were selected based on Dorr type A femora and matched first by Dorr type A and then age to a control cohort of 21 patients (11 female) at mean age of 74 years (70 to 89) who received with cemented Exeter standard stems (control group). Preoperatively, all patients had primary hip osteoarthritis and no osteoporosis as confirmed by dual X-ray absorptiometry scanning. Patients were followed with radiostereometry for evaluation of stem migration (primary endpoint), evaluation of cement quality, and Oxford Hip Score. Measurements were taken preoperatively, and at three, 12, and 24 months and a minimum five-year follow-up. Results. At three months, subsidence of the short stem -0.87 mm (95% confidence interval (CI) -1.07 to -0.67) was lower compared to the standard stem -1.59 mm (95% CI -1.82 to -1.36; p < 0.001). Both stems continued a similar pattern of subsidence until five-year follow-up. At five-year follow-up, the short stem had subsided mean -1.67 mm (95% CI -1.98 to -1.36) compared to mean -2.67 mm (95% CI -3.03 to -2.32) for the standard stem (p < 0.001). Subsidence was not influenced by preoperative bone quality (osteopenia vs normal) or cement mantle thickness. Conclusion. The standard Exeter stem had more early subsidence compared with the short Exeter stem in patients with Dorr type A femora, but thereafter a similar migration pattern of subsidence until minimum five years follow-up. Both the standard and the short Exeter stems subside. The standard stem subsides more compared to the short stem in Dorr type A femurs. Subsidence of the Exeter stems was not affected by cement mantle thickness. Cite this article: Bone Jt Open 2023;4(7):507–515


The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 229 - 234
1 Feb 2015
Choi W Lee HJ Kim D Lee C Lee BG Kim J Lee K

We performed a retrospective study to determine the effect of osteoporosis on the functional outcome of osteoporotic distal radial fractures treated with a volar locking plate. Between 2009 and 2012 a total of 90 postmenopausal women with an unstable fracture of the distal radius treated with a volar locking plate were studied. Changes in the radiological parameters of 51 patients with osteoporosis (group 1, mean age 66.9, mean T-score –3.16 (. sd.  0.56)) were not significantly different from those in 39 patients without osteoporosis (group 2, mean age 61.1, mean T-score –1.72 (. sd. 0.57)). The mean Disabilities of the Arm, Shoulder and Hand (DASH) score at final follow-up was 11.5 (. sd. 12.2) in group 1 and 10.5 (. sd.  13.25) in group 2. The mean modified Mayo wrist score at final follow-up was 79.0 (. sd.  14.04) in group 1 and 82.6 (. sd. 13.1) in group 2. However, this difference was not statistically significant (p = 0.35 for DASH score, p = 0.2 for modified Mayo wrist score). Univariable and multivariable logistic regression analysis showed that only the step-off of the radiocarpal joint was related to both a poor DASH and modified Mayo wrist score. Pearson’s correlation coefficient showed a weak negative relationship only between the T-score and the change in volar tilt (intraclass coefficient –0.26, p = 0.02). We found that osteoporosis does not have a negative effect on the functional outcome and additional analysis did not show a correlation between T-score and outcome. Cite this article: Bone Joint J 2015;97-B:229–34


Bone & Joint Research
Vol. 6, Issue 7 | Pages 452 - 463
1 Jul 2017
Wang G Sui L Gai P Li G Qi X Jiang X

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 63-B, Issue 2 | Pages 233 - 238
1 May 1981
Dickenson R Hutton W Stott

Specimens of femoral cortical bone from normal subjects and from patients with osteoporosis were mechanically tested in tension to destruction. The osteoporotic bone showed less strength and less stiffness than the normal bone; these reductions are related to the increased cavity area in osteoporosis. Further, the osteoporotic bone is not able to absorb as much energy before fracture as the normal bone; but this difference is not related to changes in cavity area


The Journal of Bone & Joint Surgery British Volume
Vol. 77-B, Issue 1 | Pages 148 - 151
1 Jan 1995
Rico H Relea P Crespo R Revilla M Villa L Arribas I Usabiaga J

We studied nutritional deficits, using as markers the levels of transferrin, retinol-binding protein, and prealbumin, in 20 women with osteoporotic hip fractures (type II), 40 women with vertebral fractures (type I), and two groups of age-matched control subjects. The concentrations of all three nutritional markers were lower in the two groups of patients than in their matched controls, and in type-I as compared with type-II osteoporosis. In the osteoporotic patients, simple linear regression showed a significant correlation between the variables which we studied (r2 ranged from 0.5 to 0.7; p < 0.001), the best correlation being between prealbumin and retinol-binding protein in type-II osteoporosis. Our results suggest that there is a more marked nutritional deficit in type-II than in type-I osteoporosis


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 5 | Pages 769 - 773
1 Nov 1987
Shifrin L Reis N Zinman H Besser M

We have reviewed 11 patients with idiopathic transient osteoporosis of the hip; the six who were women all developed the condition during pregnancy. Both simultaneous and sequential bilateral involvement were seen, but biochemical studies were consistently normal and one synovial biopsy showed only non-specific inflammation. Radioisotope bone scans and CT scans were useful to aid diagnosis. Treatment by limiting weight-bearing relieved symptoms, and spontaneous resolution was paralleled by radiographic remineralisation, usually within a few months. One patient developed a stress fracture of the hip and other areas of transient osteoporosis. A hip involved by the condition should be protected from overloading until bone density has recovered


Bone & Joint Research
Vol. 8, Issue 11 | Pages 544 - 549
1 Nov 2019
Zheng W Liu C Lei M Han Y Zhou X Li C Sun S Ma X

Objectives. The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility. Methods. Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (. http://analysis.bio-x.cn/. ) was employed. Results. The logistic regression model revealed that the C allele of rs2501431 and the G allele of rs3003336 were associated with increased OP risk, compared with those with wild genotype. However, no significant correlations were found when analyzing the association of rs4237 and rs2229579 with OP risk. The GMDR analysis suggested that the interaction model composed of two factors, rs3003336 and abdominal obesity (AO), was the best model with statistical significance (p-value from sign test (P. sign. ) = 0.012), indicating a potential gene-environment interaction between rs3003336 and AO. Overall, the two-locus models had a cross-validation consistency of 10/10 and had a testing accuracy of 0.641. Abdominally obese subjects with the AG or GG genotype have the highest OP risk, compared with subjects with the AA genotype and normal waist circumference (WC) (odds ratio (OR) 2.23, 95% confidence interval (CI) 1.54 to 3.51). Haplotype analysis also indicated that the haplotype containing the rs3003336-G and rs2501431-C alleles was associated with a statistically increased OP risk. Conclusion. Our results suggested that the C allele of rs2501431 and the G allele of rs3003336 of the CNR2 gene, interaction between rs3003336 and AO, and the haplotype containing the rs3003336-G and rs2501431-C alleles were all associated with increased OP risk. Cite this article: Bone Joint Res 2019;8:544–549


Bone & Joint Research
Vol. 9, Issue 8 | Pages 524 - 530
1 Aug 2020
Li S Mao Y Zhou F Yang H Shi Q Meng B

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated.

Cite this article: Bone Joint Res 2020;9(8):524–530.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1438 - 1440
1 Nov 2006
Niimi R Sudo A Hasegawa M Fukuda A Uchida A

Transient osteoporosis of the hip is a disorder characterised by pain, and associated with temporary osteopaenia. Although osteopaenia is the essence of the condition, data do not exist about the local bone density of the femoral neck if no medication is administered. We describe three patients who were treated with limitation of weight-bearing only. Repeated bone mineral density measurements were obtained, and that at the femoral neck was lowest two months after the onset of the condition. The mean reduction in bone mineral density when compared with an age-matched control group was 13% (3% to 24%). Spontaneous recovery was observed in all patients


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 4 | Pages 661 - 663
1 Aug 1989
Charnley R Bickerstaff D Wallace W Stevens A

In a prospective study of the measurement of osteoporosis in patients with fracture of the femoral neck, we compared a histological with a radiological method. We found no significant correlation between histological planimetry and the radiological six metacarpal hand index in patients with either cervical or trochanteric fractures. This demonstrates that metacarpal morphometry cannot predict histological osteoporosis of the iliac crest


Bone & Joint Research
Vol. 12, Issue 2 | Pages 147 - 154
20 Feb 2023
Jia Y Qi X Ma M Cheng S Cheng B Liang C Guo X Zhang F

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Methods

We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 160 - 165
1 Feb 2016
Farrier AJ C. Sanchez Franco L Shoaib A Gulati V Johnson N Uzoigwe CE Choudhury MZ

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 8 | Pages 1150 - 1156
1 Aug 2005
Hayashi K Fotovati A Ali SA Oda K Oida H Naito M

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats. Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 1 | Pages 54 - 55
1 Jan 1998
Karagkevrekis CB Ainscow DAP

We describe two patients with osteogenesis imperfecta who developed transient osteoporosis in both hips sequentially


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 2 | Pages 190 - 194
1 Mar 1987
Schnitzler C Sweet M Blumenfeld T Isaacson D

In the search for a simple method of assessing the therapeutic efficacy of sodium fluoride, a prospective study of vertebral radiography during such treatment was carried out. Treatment of osteoporosis with sodium fluoride, calcium and vitamin D was found to enhance the vertical markings of the vertebral trabecular pattern in 69% of patients. This response was graded 1 (failure), 2 (good) and 3 (excellent); Grade 2 or 3 was attained after a mean treatment period of 31.7 months. Subsequent analysis of the vertebral fracture rate revealed that new vertebral fractures had occurred only in patients with Grade 1 and not in those with Grade 2 or 3. We recommend that treatment should aim at increasing the vertebral trabecular pattern to Grade 2 or 3 and that the duration of therapy should be approximately 30 months


Bone & Joint Research
Vol. 9, Issue 11 | Pages 798 - 807
2 Nov 2020
Brzeszczyńska J Brzeszczyński F Hamilton DF McGregor R Simpson AHRW

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 188 - 191
1 Mar 2021
Nicholson T Scott A Newton Ede M Jones SW


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 62 - 68
1 Jan 2024
Harris E Clement N MacLullich A Farrow L

Aims

Current levels of hip fracture morbidity contribute greatly to the overall burden on health and social care services. Given the anticipated ageing of the population over the coming decade, there is potential for this burden to increase further, although the exact scale of impact has not been identified in contemporary literature. We therefore set out to predict the future incidence of hip fracture and help inform appropriate service provision to maintain an adequate standard of care.

Methods

Historical data from the Scottish Hip Fracture Audit (2017 to 2021) were used to identify monthly incidence rates. Established time series forecasting techniques (Exponential Smoothing and Autoregressive Integrated Moving Average) were then used to predict the annual number of hip fractures from 2022 to 2029, including adjustment for predicted changes in national population demographics. Predicted differences in service-level outcomes (length of stay and discharge destination) were analyzed, including the associated financial cost of any changes.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 216 - 216
1 Sep 2012
Fat DL Kennedy J Galvin R O'Brien F Mullett H
Full Access

Introduction. Fractures of the proximal humerus represent a major osteoporotic burden. Recent developments in CT imaging have emphasized the importance of cortical bone thickness distribution in the prevention and management of fragility fractures. We aimed to experimentally define the CT density of cortical bone in the proximal humerus for building cortical geometry maps. Methods. With ethical approval we used ten fresh frozen human proximal humeri. These were stripped of all soft tissue and high resolution CT images were then taken. The humeral heads were then subsequently resected to allow access to the metaphyseal area. Using curettes, cancellous bone was removed down to hard cortical bone. Another set of CT images of the reamed specimen was then taken. Using CT imaging software and a CAD interface we then compared cortical contours at different CT density thresholds to the reference inner cortical contour of our reamed specimens. Working with 3D model representations of these cortical maps, we were able to accurately make distance comparison analyses based on different CT thresholds. Results. We could compute a single closest value at 700HU. There was no difference found in the HU based contours generated along the 500HU–900HU pixels (p=1.000). The contours were significantly different to those generated at 300HU, 400HU, 1000HU and 1100HU. Discussion/conclusion: A Hounsfield range of 500 to 900 HU can accurately depict cortical bone geometry in the proximal humerus. Thresholding outside this range leads to statistically significant inaccuracies. Our results concur with a similar range reported in the literature for the proximal femur. Knowledge of regional variations in cortical bone thickness has direct implications for basic science studies on osteoporosis and its treatment, but is also important for the orthopaedic surgeon since our decision for treatment options is often guided by local bone quality


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 7 | Pages 1069 - 1074
1 Sep 2001
Little DG Cornell MS Briody J Cowell CT Arbuckle S Cooke-Yarborough CM

We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits. Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm. 2. ) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p< 0.05). Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate. Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 97 - 102
1 Jan 2022
Hijikata Y Kamitani T Nakahara M Kumamoto S Sakai T Itaya T Yamazaki H Ogawa Y Kusumegi A Inoue T Yoshida T Furue N Fukuhara S Yamamoto Y

Aims

To develop and internally validate a preoperative clinical prediction model for acute adjacent vertebral fracture (AVF) after vertebral augmentation to support preoperative decision-making, named the after vertebral augmentation (AVA) score.

Methods

In this prognostic study, a multicentre, retrospective single-level vertebral augmentation cohort of 377 patients from six Japanese hospitals was used to derive an AVF prediction model. Backward stepwise selection (p < 0.05) was used to select preoperative clinical and imaging predictors for acute AVF after vertebral augmentation for up to one month, from 14 predictors. We assigned a score to each selected variable based on the regression coefficient and developed the AVA scoring system. We evaluated sensitivity and specificity for each cut-off, area under the curve (AUC), and calibration as diagnostic performance. Internal validation was conducted using bootstrapping to correct the optimism.


Bone & Joint Research
Vol. 11, Issue 1 | Pages 12 - 22
13 Jan 2022
Zhang F Rao S Baranova A

Aims

Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Methods

Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases.


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 2 | Pages 210 - 216
1 Mar 1993
Hofmann S Engel A Neuhold A Leder K Kramer J Plenk H

Bone-marrow oedema syndrome (BMOS) of the hip gives a characteristic MRI pattern, in association with severe pain, non-specific focal loss of radiological density and a positive bone scan. In our MRI-controlled study, nine patients with non-traumatic BMOS in ten hips all had core decompression. Bone-marrow pressure measurements and intraosseous venography in five cases showed pathological values. All patients had immediate relief of pain, with return of MRI signals to normal after three months. Regular review was continued for at least 24 months with serial clinical radiological and MRI assessment. At a mean follow-up of 33 months all patients remained free of pain with normal radiographs and MR scans. The histological evaluation of undecalcified sections obtained from eight core decompressions confirmed the presence of bone-marrow oedema, with necrotic and reparative processes involving bone and marrow similar to those of early avascular necrosis but with no evidence of 'osteoporosis'. These findings support the assumption that BMOS may be the initial phase of non-traumatic avascular necrosis. In most patients BMOS will have a self-limiting course, but the duration of symptoms may be reduced by core decompression treatment


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 3 | Pages 294 - 303
1 Mar 2009
Lindner T Kanakaris NK Marx B Cockbain A Kontakis G Giannoudis PV

Failure of fixation is a common problem in the treatment of osteoporotic fractures around the hip. The reinforcement of bone stock or of fixation of the implant may be a solution. Our study assesses the existing evidence for the use of bone substitutes in the management of these fractures in osteoporotic patients. Relevant publications were retrieved through Medline research and further scrutinised. Of 411 studies identified, 22 met the inclusion criteria, comprising 12 experimental and ten clinical reports. The clinical studies were evaluated with regard to their level of evidence. Only four were prospective and randomised.

Polymethylmethacrylate and calcium-phosphate cements increased the primary stability of the implant-bone construct in all experimental and clinical studies, although there was considerable variation in the design of the studies. In randomised, controlled studies, augmentation of intracapsular fractures of the neck of the femur with calcium-phosphate cement was associated with poor long-term results. There was a lack of data on the long-term outcome for trochanteric fractures. Because there were only a few, randomised, controlled studies, there is currently poor evidence for the use of bone cement in the treatment of fractures of the hip.


Bone & Joint 360
Vol. 11, Issue 1 | Pages 52 - 52
1 Feb 2022


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 2 | Pages 311 - 311
1 Mar 2003
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 743 - 743
1 Jul 1998
WUISMAN PIJM NOORDA RJP


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 3 | Pages 432 - 436
1 May 1998
Terauchi M Shirakura K Katayama M Higuchi H Takagishi K

We studied 37 patients with varus osteoarthritis of the knee to determine the influence of the bone mineral density (BMD) on the varus deformity. There were 15 men (21 knees) and 22 women (38 knees). The mean age of the men was 69 years and of the women 68 years. BMD was measured in the L1–L4 spinal region using dual X-ray absorptiometry.

In the women a low level of BMD was associated with varus deformity originating at the proximal tibia, but a high level was predominantly linked with deformity originating in the joint space. Similar findings were obtained in the men.

Our results suggest that a low BMD predisposes to trabecular microfractures and consequently increased stress on the articular cartilage. A low BMD does not preclude osteoarthritic change in the knee.


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 6 | Pages 993 - 994
1 Nov 1994
Doury P


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 3 | Pages 450 - 452
1 May 1993
Sarangi P Ward A Smith E Staddon G Atkins R

We made a prospective study of the incidence and natural history of algodystrophy and associated changes in bone mineral density in the ankles and feet of 60 consecutive patients who had suffered unilateral fractures of the tibial shaft. At bone union, 18 patients showed signs of algodystrophy. Its development was independent of the type of fracture management and of the severity of injury. Patients with algodystrophy lost significantly more bone mineral than did those without but the degree of this loss was independent of the type of treatment and of the time to fracture union. In most cases the symptoms resolved within six months of fracture union but in four patients they were still present at one year and two of these had not returned to work.


The Journal of Bone & Joint Surgery British Volume
Vol. 65-B, Issue 2 | Pages 195 - 198
1 Mar 1983
Jhamaria N Lal K Udawat M Banerji P Kabra S

Radiographs of the foot and hip in 61 patients with fractures of the upper end of femur have been studied, noting the progressive loss of bone trabeculae with age. The trabecular pattern in the calcaneum (expressed as the calcaneal index) closely parallels that in the upper end of the femur (Singh's index) and is easier to assess. Both indices have a significant correlation with age.


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 3 | Pages 465 - 465
1 Apr 2000
Fogelman I


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 5 | Pages 773 - 774
1 Nov 1987
Keys G Walters J


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 3 | Pages 345 - 347
1 May 1994
Smith R


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 4 | Pages 671 - 676
1 Aug 1989
Takashima T Kawai K Hirohata K Miki A Mizoguti H Cooke T

We studied the morphology of the haversian canals in the osteopenic cortical bone of the medial femoral neck from patients with rheumatoid arthritis and compared the findings with those in patients with osteoarthritis and with uncomplicated coxa valga. In the rheumatoid bone, the diameters of the canals were larger and many more contained osteoclasts. Fewer haversian canals showed only lining cells than in the osteoarthritic or coxa valga patients. In bone from rheumatoid patients, especially in canals with osteoclasts, small blood vessels were frequently lined by tall endothelial cells with an infiltration of mononuclear cells. These morphological differences are discussed with reference to the possible mechanisms of loss of cortical bone in rheumatoid arthritis and other conditions.


Full Access

Osteoporosis can cause significant disability and cost to health services globally. We aim to compare risk fractures for both osteoporosis and fractures at the L1-L4 vertebrae (LV) and the neck of femurs (NOFs) in patients referred for DEXA scan in the North-West of England. Data was obtained from 31546 patients referred for DEXA scan in the North-West of England between 2004 and 2011. Demographic data was retrospectively analysed using STATA, utilising chi-squared and t-tests. Logistical models were used to report odds ratios for risk factors included in the FRAX tool looking for differences between osteoporosis and fracture risk at the LV and NOFs. In a study involving 2530 cases of LV fractures and 1363 of NOF fractures, age was significantly linked to fractures and osteoporosis at both sites, with a higher risk of osteoporosis at NOFs compared to LV. Height provided protection against fractures and osteoporosis at both sites, with a more pronounced protective effect against osteoporosis at NOFs. Weight was more protective for NOF fractures, while smoking increased osteoporosis risk with no site-specific difference. Steroids were unexpectedly protective for fractures at both sites, with no significant difference, while alcohol consumption was protective against osteoporosis at both sites and associated with increased LV fracture risk. Rheumatoid arthritis increased osteoporosis risk in NOFs and implied a higher fracture risk, though not statistically significant compared to LV. Results summarised in Table 1. Our study reveals that established osteoporosis and fracture risk factors impact distinct bony sites differently. Age and rheumatoid arthritis increase osteoporosis risk more at NOFs than LV, while height and steroids provide greater protection at NOFs. Height significantly protects LV fractures, with alcohol predicting them. Further research is needed to explore risk factors’ impact on additional bony sites and understand the observed differences’ pathophysiology. For any figures or tables, please contact the authors directly


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims. Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. Methods. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Results. Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Conclusion. Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis. Cite this article: Bone Joint Res 2023;12(11):677–690


The Bone & Joint Journal
Vol. 104-B, Issue 11 | Pages 1249 - 1255
1 Nov 2022
Williamson TK Passfall L Ihejirika-Lomedico R Espinosa A Owusu-Sarpong S Lanre-Amos T Schoenfeld AJ Passias PG

Aims. Postoperative complication rates remain relatively high after adult spinal deformity (ASD) surgery. The extent to which modifiable patient-related factors influence complication rates in patients with ASD has not been effectively evaluated. The aim of this retrospective cohort study was to evaluate the association between modifiable patient-related factors and complications after corrective surgery for ASD. Methods. ASD patients with two-year data were included. Complications were categorized as follows: any complication, major, medical, surgical, major mechanical, major radiological, and reoperation. Modifiable risk factors included smoking, obesity, osteoporosis, alcohol use, depression, psychiatric diagnosis, and hypertension. Patients were stratified by the degree of baseline deformity (low degree of deformity (LowDef)/high degree of deformity (HighDef): below or above 20°) and age (Older/Younger: above or below 65 years). Complication rates were compared for modifiable risk factors in each age/deformity group, using multivariable logistic regression analysis to adjust for confounders. Results. A total of 480 ASD patients met the inclusion criteria. By two years, complication rates were 72% ≥ one complication, 28% major, 21% medical, 27% surgical, 11% major radiological, 8% major mechanical, and 22% required reoperation. Younger LowDef patients with osteoporosis were more likely to suffer either a major mechanical (odds ratio (OR) 5.9 (95% confidence interval (CI) 1.1 to 36.9); p = 0.048) or radiological complication (OR 7.0 (95% CI 1.9 to 25.9); p = 0.003). Younger HighDef patients were much more likely to develop complications if obese, especially major mechanical complications (OR 2.8 (95% CI 1.1 to 8.6); p = 0.044). Older HighDef patients developed more complications when diagnosed with depression, including major radiological complications (OR 3.5 (95% CI 1.1 to 10.6); p = 0.033). Overall, a diagnosis of depression proved to be a risk factor for the development of major radiological complications (OR 2.4 (95% CI 1.3 to 4.5); p = 0.005). Conclusion. Certain modifiable patient-related factors, especially osteoporosis, obesity, and mental health status, are associated with an increased risk of complications after surgery for spinal deformity. Surgeons should look for these conditions when assessing a patient for surgery, and optimize them to the fullest extent possible before proceeding to surgical correction so as to minimize the prospect of postoperative morbidity. Cite this article: Bone Joint J 2022;104-B(11):1249–1255


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 22 - 22
7 Aug 2024
Saunders F Parkinson J Aspden R Cootes T Gregory J
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Background. Lateral lumbar spine statistical shape models (SSM) have been used previously to describe associations with osteoarthritis and back pain. However, associations with factors such as osteoporosis, menopause and parity have not been explored. Methods and Results. A 143-point SSM, describing L1 to the top of L5, was applied to lateral spine iDXA scans from UK Biobank. Associations with self-reported osteoporosis, menopause, parity and back pain and the first 10 modes of variation were examined using adjusted binary logistic regression or linear regression (adjusted for age, height, weight and total spine BMD). We report odds ratios with 95% confidence intervals for each standard deviation change in mode. Complete data were available for 2494 women. Mean age was 61.5 (± 7.4) years. 1369 women reported going through menopause, 96 women self-reported osteoporosis and 339 women reported chronic back pain. 80% of women reported at least 1 live birth. Lumbar spine shape was not associated with back pain in this cohort. Two modes were associated with menopause (modes 1 & 2), 1 mode with parity (mode 1) and 2 modes with osteoporosis (modes 3 & 5). Mode 1 (43.6% total variation), describing lumbar curvature was positively associated with both menopause [OR 1.15 95% CI 1.00–1.33, p=0.05] and parity [OR 1.058 95% CI 1.03–1.0, p=0.01]. Mode 3, describing decreased vertebral height was positively associated with osteoporosis [OR 1.40 95% CI 1.14–1.73, p=0.001]. Conclusion. Menopause and parity were associated with a curvier lumbar spine and osteoporosis with decreased vertebral height. Shape was not associated with back pain. No conflicts of interest.  . Sources of funding. Wellcome Trust collaborative award ref 209233


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 15 - 15
11 Apr 2023
Li H Chen H
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Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation. In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, bone marrow-derived macrophages (BMM) and bone marrow mesenchymal stem cell (BMSC) of KO and C57BL6/J mice were extracted to test their osteogenic and osteoclastic abilities. We then created osteoclastic 11β-HSD1 elimination mice (Ctsk::11β-HSD1fl/fl) and treated them with OVX. Micro-CT analysis, H&E, immunofluorescence staining, and qPCR were performed. Finally, we conducted the high-throughput sequencing to find out 11β-HSD1 and osteoclast activation related genes. We collected 6w samples after modeling. We found that KO mice were resistant to loss of bone trabeculae. The same effect was observed in osteoclastic 11β-HSD1 elimination mice. Meanwhile, BVT-2733, a classic inhibitor of 11β-HSD1, inhibited the osteoclast effect of cells without affecting osteogenic effect in vitro. High-throughput sequencing suggested that glucocorticoid receptor (GR) may play a key role in the activation of osteoclasts, which was verified by immunofluorescence staining and WB in vivo and in vitro. In the process of osteoporosis, 11β-HSD1 expression of osteoclasts is abnormally increased, which may be a new target for inhibiting osteoclast activation and treating osteoporosis


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 72 - 72
7 Nov 2023
Khumalo M
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Low-energy fractures complications are a major public health issue that make osteoporosis even worse. In sub-Saharan Africa, the prevalence of osteoporosis varies from 18.2% to 65.8%. There was no change in bone mineral density between HIV-infected and non-HIV-infected women in Sub-Saharan Africa, where HIV is widespread. Other investigations that demonstrated that HIV-infected people had poor BMD both before and after starting anti-retroviral treatment did not consistently show a low BMD finding. Inflammation-mediated bone remodelling has been associated with low BMD in HIV-infected patients. Antiretroviral Therapy has been demonstrated to exacerbate bone loss in addition to the pre-existing intrinsic risk of developing osteoporosis. Question: Is there loss of bone in HIV-infected patients before initiating ART?. The patients who were HIV-positive and enrolled in the ADVANCE research were retrospectively reviewed on a desk. All of the 1053 individuals in the ADVANCE research had a DXA scan performed to evaluate BMD as part of the initial screening and recruitment approach. The ADVANCE research enrolled HIV-positive people and randomly assigned them to three ART arms. A total of 400 patients were reviewed. Of these 400 records reviewed, 62.3% were female. 80% of the participants were younger than 40 years old, and 3% were older than 50 years. 82% were virally suppressed with less than 50 viral copies. The prevalence of osteopenia was 25.5% and osteoporosis was 2.8%, observed in predominantly African female participants aged between 30 and 39 years. The findings of this study confirm that there is pre-existing bone loss among HIV-infected ART naïve individuals. Approximately 28.3% in our study had clinically confirmed evidence of bone loss and of these, 2.8% of the entire cohort had osteoporosis. Bone loss was most prevalent in black females who are virologically suppressed


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 55 - 55
11 Apr 2023
Raina D Markeviciute V Arvidsson L Törnquist E Stravinskas M Kok J Jacobson I Liu Y Tengattini A Sezgin E Vater C Zwingenberger S Isaksson H Tägil M Tarasevicius S Lidgren L
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Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 53 - 53
4 Apr 2023
Hipps D Dobson P Warren C Russell O Turnbull D Deehan D Lawless C
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We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 147 - 147
4 Apr 2023
Tohidnezhad M Kubo Y Gonzalez J Weiler M Pahlavani H Szymanski K Mirazaali M Pufe T Jahr H
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Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model. Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05. When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice. Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 58 - 58
17 Nov 2023
Huang D Buchanan F Clarke S
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Abstract. Objectives. Osteoporotic fractures tend to be more challenging than fractures in healthy bone and the efficacy of metal screw fixation decreases with decreasing bone mineral density making it more difficult for such screws to gain purchase. This leads to increased complication rates such as malunion, non-union and implant failure (1). Bioresorbable polymer devices have seen clinical success in fracture fixation and are a promising alternative for metallic devices but are rarely used in the osteoporotic population. To address this, we are developing a system that may allow osteoporotic patients to avail of bioresorbable devices (2) but it is important to establish if patients have any reservations about having a plastic resorbable device instead of a metal one. Therefore the aim of this study was to explore the acceptability of bioresorbable fracture fixation devices to people with osteoporosis. Methods. A cross sectional descriptive study was conducted in a UK wide population using convenience sampling. An online survey comprising nine survey questions and nine demographic questions was developed in Microsoft Teams and tested for face validity in a small pilot study (n=6). Following amendments and ethical approval, the survey was distributed by the Royal Osteoporosis Society on their website and social media platforms. People were invited to take part if they lived in the UK, were over 18 years old and had been diagnosed with osteoporosis. The survey was open for three weeks in May 2023. Responses were analysed using descriptive statistics. Results. There were 112 responses. Eight participants had not been diagnosed with osteoporosis and therefore did not meet the study criteria. Of the remaining 104, 102 were female and 2 were male and 102 were white (2 chose not to disclose their ethnicity). The majority of participants were aged 55–64 (34.6%) or 65–74 (37.5%), were college/university educated (38.5%) and had previously sustained a fragility fracture (52.9%). Only 3.9% of participants had heard of bioresorbable fracture fixation devices compared to 62.5% for metal devices. Most people were unsure if they would trust one type of device over the other (58.7%) and would ask for more information if their surgeon were to suggest using a bioresorbable device to fix their fracture (61.5%). The most commonly reported concerns were about device safety and efficacy: toxicity of the degradation products and the device breaking down too early before the fracture had healed. Two participants cited environmental concerns about increased use of plastics as a reason they would decline such a device. Conclusions. As expected, participants had little to no knowledge of bioresorbable polymer fixation devices. In general, they were willing to be guided by their surgeon but would require supporting information on the safety and efficacy of their long-term use. The results of this study show that it will be important to have relevant and understandable information to give patients when recommending these devices as treatments to ensure and support a shared-decision approach to patient care. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426


Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims. Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 16 - 16
2 Jan 2024
Lipreri M Pasquarelli A Scelfo D Baldini N Avnet S
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Osteoporosis is a progressive, chronic disease of bone metabolism, characterized by decreased bone mass and mineral density, predisposing individuals to an increased risk of fractures. The use of animal models, which is the gold standard for the screening of anti-osteoporosis drugs, raises numerous ethical concerns and is highly debated because the composition and structure of animal bones is very different from human bones. In addition, there is currently a poor translation of pre-clinical efficacy in animal models to human trials, meaning that there is a need for an alternative method of screening and evaluating new therapeutics for metabolic bone disorders, in vitro. The aim of this project is to develop a 3D Bone-On-A-Chip that summarizes the spatial orientation and mutual influences of the key cellular components of bone tissue, in a citrate and hydroxyapatite-enriched 3D matrix, acting as a 3D model of osteoporosis. To this purpose, a polydimethylsiloxane microfluidic device was developed by CAD modelling, stereolithography and replica molding. The device is composed by two layers: (i) a bottom layer for a 3D culture of osteocytes embedded in an osteomimetic collagen-enriched matrigel matrix with citrate-doped hydroxyapatite nanocrystals, and (ii) a upper layer for a 2D perfused co-culture of osteoblasts and osteoclasts seeded on a microporous PET membrane. Cell vitality was evaluated via live/dead assay. Bone deposition and bone resorption was analysed respectively with ALP, Alizarin RED and TRACP staining. Osteocytes dendrite expression was evaluated via immunofluorescence. Subsequently, the model was validated as drug screening platform inducing osteocytes apoptosis and administrating standard anti-osteoporotic drugs. This device has the potential to substitute or minimize animal models in pre-clinical studies of osteoporosis, contributing to pave the way for a more precise and punctual personalized treatment


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 881 - 889
1 Jul 2020
Frank FA Niehaus R Borbas P Eid K

Aims. Conservative treatment of moderately displaced proximal humeral head fractures yields good clinical results, but secondary fragment displacement may occur. Identification of those fractures at risk of displacement may influence initial decision-making. Methods. A total of 163 shoulders in 162 patients with conservatively treated isolated proximal humeral fractures were included. The fractures occurred between January 2015 and May 2018. The mean age of the patients was 69 years (26 to 100) and the mean follow-up was 144 days (42 to 779). The fractures were classified according to Neer. Scores for osteoporosis (Tingart, Deltoid Tuberosity Index (DTI)) and osteoarthritis (OA) of the glenohumeral joint were assessed. Translation of the head on follow-up radiographs of more than 10 mm was defined as displacement. Eccentric head index (EHI) describes the offset of the humeral head centre in relation to the diaphyseal axis. The ratio was estimated on anteroposterior (AP) and Neer views. Medial hinge was considered intact if the medial cortex proximal and distal to the fracture was in line on AP view. Results. Secondary fracture displacement occurred in 41 patients (25.2%). Clinical risk factors were alcohol abuse (odds ratio (OR) 6.8; 95% confidence interval (CI) 1.3 to 36; p = 0.025) and previously diagnosed osteoporosis (OR 4.6; 95% CI 0.6 to 34; p = 0.136). Age (OR 1.1; 95% CI 1.0 to 1.1; p = 0.003) and sex (OR 0.9; 95% CI 0.3 to 2.8; p = 0.867) were not independent factors. Radiological risk factors were OA grade 3 (OR 16.4; 95% CI 0.25 to 37.6; p = 0.107) and osteoporosis with the DTI (OR 10; 95% CI 0.8 to 250; p = 0.031) being more predictive than the Tingart score (OR 2.3; 95% CI 0.8 to 4.7; p = 0.041). A high EHI (AP/Neer > 0.4, OR 18.9; 95% CI 2.1 to 30.9/3.0; 95% CI 1.1 to 8.0; p = 0.002/p = 0.033) and a disrupted medial hinge (OR 3.7; 95% CI 1.1 to 12.6; p = 0.039) increased the risk of secondary displacement significantly. Neer classification had no influence. Conclusion. During conservative treatment, a quarter of patients showed secondary fracture displacement of at least 10 mm. Patients with alcohol abuse, severe OA, and osteoporosis are at risk. Newly defined EHI and disrupted medial hinge are relevant predictors for secondary displacement. Cite this article: Bone Joint J 2020;102-B(7):881–889


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 94 - 94
1 Nov 2021
Chen Y Lian W Wang F
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Introduction and Objective. Senescent bone cell overburden accelerates osteoporosis. Epigenetic alteration, including microRNA signalling and DND methylation, is one of prominent features of cellular senescence. This study aimed to investigate what role microRNA-29a signalling may play in the development of senile osteoporosis. Materials and Methods. Bone biopsy and serum were harvested from 13 young patients and 15 senior patients who required spine surgery. Bone mass, microstructure, and biomechanics of miR-29a knockout mice (miR-29aKO) and miR-29a transgenic mice (miR-29aTg) were probed using mCT imaging and three-point bending material test. Senescent cells were probed using senescence-associated b-galactosidase (SA-b-gal) staining. Transcriptomic landscapes of osteoblasts were characterized using whole genome microarray and KEGG bioinformatics. miR-29a and senescence markers p16. INK4a. , p21. Waf/cipl. and inflammatory cytokines were quantified using RT-PCR. DNA methylome was probed using methylation-specific PCR and 5-methylcytosine immunoblotting. Results. Senescent osteoblast overburden, DNA hypermethylation and oxidative damage together with significant decreases in serum miR-29a levels were present in bone specimens of aged patients. miR-29aKO mice showed a phenotype of skeletal underdevelopment, low bone mineral density and weak biomechanics. miR-29a knockout worsened age-induced bone mass and microstructure deterioration. Of note, aged miR-29aTg mice showed less bone loss and fatty marrow than aged wild-type mice. Transgenic overexpression of miR-29s compromised age-dysregulated osteogenic differentiation capacity of bone-marrow mesenchymal cells. In vitro, miR-29a promoted transcriptomic landscapes of antioxidant proteins in osteoblasts. The microRNA interrupted DNA methyltransferase (Dnmt3b)-mediated DNA methylation, inhibiting reactive oxygen radicals burst, IL-6 and RANKL production, and a plethora of senescent activity, including increased p16. INK4a. , p21. Waf/cipl. signalling and SA-b-gal activity. Conclusions. miR-29a loss is correlated with human age-mediated osteoporosis. miR-29a signalling is indispensable in bone mase homeostasis and microstructure integrity. Gain of miR-29a function is advantageous to delay age-induced bone loss through promoting antioxidant proteins to inhibit DNA hypermethylation-mediated osteoblast senescence. Collective investigations shine light onto the anabolic effects miR-29a signalling to bone integrity and highlight a new epigenetic protection strategy through controlling microRNA signalling to delay osteoblast senescence and senile osteoporosis development


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 123 - 123
2 Jan 2024
Hofmann S
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Metabolic bone diseases, such as osteoporosis and osteopetrosis, result from an imbalanced bone remodeling process. In vitro bone models are often used to investigate either bone formation or resorption independently, while in vivo, these processes are coupled. Combining these processes in a co-culture is challenging as it requires finding the right medium components to stimulate each cell type involved without interfering with the other cell type's differentiation. Furthermore, differentiation stimulating factors often comprise growth factors in supraphysiological concentrations, which can overshadow the cell-mediated crosstalk and coupling. To address these challenges, we aimed to recreate the physiological bone remodeling process, which follows a specific sequence of events starting with cell activation and bone resorption by osteoclasts, reversal, followed by bone formation by osteoblasts. We used a mineralized silk fibroin scaffold as a bone-mimetic template, inspired by bone's extracellular matrix composition and organization. Our model supported osteoclastic resorption and osteoblastic mineralization in the specific sequence that represents physiological bone remodeling. We also demonstrated how culture variables, such as different cell ratios, base media, and the use of osteogenic/osteoclast supplements, and the application of mechanical load, can be adjusted to represent either a high bone turnover system or a self-regulating system. The latter system did not require the addition of osteoclastic and osteogenic differentiation factors for remodeling, therefore avoiding growth factor use. Our in vitro model for bone remodeling has the potential to reduce animal experiments and advance in vitro drug development for bone remodeling pathologies like osteoporosis. By recreating the physiological bone remodeling cycle, we can investigate cell-cell and cell-matrix interactions, which are essential for understanding bone physiology and pathology. Furthermore, by tuning the culture variables, we can investigate bone remodeling under various conditions, potentially providing insights into the mechanisms underlying different bone disorders


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 94 - 94
2 Jan 2024
Lin Y Lian W Chen Y Jahr H Wang F
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Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity. Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining. HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts. Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity


Bone & Joint Research
Vol. 10, Issue 1 | Pages 51 - 59
1 Jan 2021
Li J Ho WTP Liu C Chow SK Ip M Yu J Wong HS Cheung W Sung JJY Wong RMY

Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results. A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion. Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51–59


Aims. Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation. Methods. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay. Results. The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs. Conclusion. APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression. Cite this article: Bone Joint Res 2023;12(8):476–485


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_4 | Pages 17 - 17
3 Mar 2023
Warder H Semple A Johnson DS
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A hip fracture represents the extreme end of osteoporosis, placing a significant burden on secondary care, society, and the individual patient. The National Hip Fracture Database (NHFD) reports each hospital's attainment of the BPT with other measures, along with reporting outcomes. There is clearly wide variability in provision of orthogerriatrician (OG) services across the dataset. Unfortunately, despite overwhelming evidence that provision of an OG service is of benefit, it is presently challenging to recruit to this important specialty within the UK. Publicly available reports from the NHFD were obtained for each of the 177 participating hospitals for 2017. This was matched with information held within the annual NHFD Facilities Audit for the same period, which include hours of OG support for each hospital. This information was combined with a Freedom of Information request made by email to each hospital for further details concerning OG support. The outcome measures used were Length of Stay (LoS), mortality, and return to usual residence. Comparison was made with provision of OG services by use of Pearson's correlation coefficient. In addition, differences in services were compared between the 25% (44) hospitals delivering outcomes at the extremes for each measure. Attainment of BPT correlated fairly with LoS (−0.48) and to less of a degree with mortality (−0.1) and return home (0.05). Perioperative medical assessment contributed very strongly with BPT attainment (0.75). In turn perioperative medical assessment correlated fairly with LoS (−0.40) and mortality (−0.23) but not return home (0.02). Provision of perioperative medical assessment attainment was correlated fairly with total OG minutes available per new patient (0.22), total OG minutes available per patient per day (0.29) and number of days per week of OG cover (0.34); with no link for number of patients per orthogeriatrician (0.01). Mortality for the best units were associated with 30% more consultant OG time available per patient per day, and 51% more OG time available per patient. Units returning the most patients to their usual residence had little association with OG time, although had 59% fewer patients per OG, the best units had a 19% longer LoS. For all three measures results for the best had on average 0.5 days per week better routine OG access. There is no doubt that good quality care gives better results for this challenging group of patients. However, the interaction of BPT, other care metrics, level of OG support and patient factors with outcomes is complex. We have found OG time available per patient per day appears to influence particularly LoS and mortality. Options to increase OG time per patient include reducing patient numbers (ensuring community osteoporosis/falls prevention in place, including reducing in-patient falls); increasing OG time across the week (employing greater numbers/spreading availability over 7 days per week); and reducing LoS. A reduction in LoS has the largest effect of increasing OG time, and although it is dependent on OG support, it is only fairly correlated with this and many other factors play a part, which could be addressed in units under pressure


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 59 - 59
1 Mar 2021
Kou C Lian W Wang F
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Glucocorticoid excess is shown to deteriorate bone tissue integrity, increasing the risk of osteoporosis. Marrow adipogenesis at cost of osteogenesis is a prominent feature of this osteoporosis condition. Epigenetic pathway histone deacetylase (HDAC)-mediated histone acetylation regulates osteogenic activity and bone mass. This study is aimed to figure out what role of acetylated histone reader bromodomain-containing protein 4 (BRD4) did play in glucocorticoid-induced osteoporosis. Bone-marrow mesenchymal stem cells were incubated in osteogenic medium with or without 1 μM dexamethasone. Mineralized matrix and adipocyte formation were probed using von Kossa and Nile Red O staining, respectively. Osteogenic and adipogenic marker expression were quantified using RT-PCR. The binding of acetylated histone to promoter of transcription factors were detected using chromatin immunoprecipitation-PCR. Bone mineral density and microstructure in osteoporotic bone were quantified with microCT system. Glucocorticoid repressed osteogenic transcription factor Runx2 expression and mineralized matrix formation along with a low level of acetylated lysine 9 at histone 3 (H3K9ac), whereas BRD4 signaling and adipocytic formation were increased in cell cultures. BRD4 knockdown reversed the H3K9ac enrichment in Runx2 promoter and osteogenesis, but downregulated adipogenic differentiation. Silencing BRD4 attenuated H3K9ac occupancy in forkhead box P1 (Foxp1) relevant to lipid metabolism upon glucocorticoid stress. Foxp1 interference downregulated adipogenic activities of glucocorticoid-treated cells. In vivo, treatment with BRD4 inhibitor JQ-1 compromised the glucocorticoid-induced bone mineral density loss, spare trabecular structure, and fatty marrow, as well as improved biomechanical properties of bone tissue. Taken together, BRD4-mediated Foxp1 pathways drive mesenchymal stem cells shifting toward adipocytic cells rather than osteogenic cells to aggravates excessive marrow adipogenesis in the process of glucocorticoid-induced osteoporosis. Pharmacological inhibition of BRD4 signaling protects bone tissue from bone loss and fatty marrow in glucocorticoid-treated mice. This study conveys a new molecular insight into epigenetic regulation of osteogenesis and adipogenesis in osteoporotic skeleton and highlight the remedial effect of BRD4 inhibitor on glucocorticoid-induced bone loss


Aims. There are concerns regarding nail/medullary canal mismatch and initial stability after cephalomedullary nailing in unstable pertrochanteric fractures. This study aimed to investigate the effect of an additional anteroposterior blocking screw on fixation stability in unstable pertrochanteric fracture models with a nail/medullary canal mismatch after short cephalomedullary nail (CMN) fixation. Methods. Eight finite element models (FEMs), comprising four different femoral diameters, with and without blocking screws, were constructed, and unstable intertrochanteric fractures fixed with short CMNs were reproduced in all FEMs. Micromotions of distal shaft fragment related to proximal fragment, and stress concentrations at the nail construct were measured. Results. Micromotions in FEMs without a blocking screw significantly increased as nail/medullary canal mismatch increased, but were similar between FEMs with a blocking screw regardless of mismatch. Stress concentration at the nail construct was observed at the junction of the nail body and lag screw in all FEMs, and increased as nail/medullary canal mismatch increased, regardless of blocking screws. Mean stresses over regions of interest in FEMs with a blocking screw were much lower than regions of interest in those without. Mean stresses in FEMs with a blocking screw were lower than the yield strength, yet mean stresses in FEMs without blocking screws having 8 mm and 10 mm mismatch exceeded the yield strength. All mean stresses at distal locking screws were less than the yield strength. Conclusion. Using an additional anteroposterior blocking screw may be a simple and effective method to enhance fixation stability in unstable pertrochanteric fractures with a large nail/medullary canal mismatch due to osteoporosis. Cite this article: Bone Joint Res 2022;11(3):152–161


Bone & Joint Research
Vol. 7, Issue 7 | Pages 468 - 475
1 Jul 2018
He Q Sun H Shu L Zhu Y Xie X Zhan Y Luo C

Objectives. Researchers continue to seek easier ways to evaluate the quality of bone and screen for osteoporosis and osteopenia. Until recently, radiographic images of various parts of the body, except the distal femur, have been reappraised in the light of dual-energy X-ray absorptiometry (DXA) findings. The incidence of osteoporotic fractures around the knee joint in the elderly continues to increase. The aim of this study was to propose two new radiographic parameters of the distal femur for the assessment of bone quality. Methods. Anteroposterior radiographs of the knee and bone mineral density (BMD) and T-scores from DXA scans of 361 healthy patients were prospectively analyzed. The mean cortical bone thickness (CBTavg) and the distal femoral cortex index (DFCI) were the two parameters that were proposed and measured. Intra- and interobserver reliabilities were assessed. Correlations between the BMD and T-score and these parameters were investigated and their value in the diagnosis of osteoporosis and osteopenia was evaluated. Results. The DFCI, as a ratio, had higher reliability than the CBTavg. Both showed significant correlation with BMD and T-score. When compared with DFCI, CBTavg showed better correlation and was better for predicting osteoporosis and osteopenia. Conclusion. The CBTavg and DFCI are simple and reliable screening tools for the prediction of osteoporosis and osteopenia. The CBTavg is more accurate but the DFCI is easier to use in clinical practice. Cite this article: Q-F. He, H. Sun, L-Y. Shu, Y. Zhu, X-T. Xie, Y. Zhan, C-F. Luo. Radiographic predictors for bone mineral loss: Cortical thickness and index of the distal femur. Bone Joint Res 2018;7:468–475. DOI: 10.1302/2046-3758.77.BJR-2017-0332.R1


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 58 - 58
1 Mar 2021
Chen Y Lian W Wang F
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Chronic glucocorticoid use causes osteogenesis loss, accelerating the progression of osteoporosis. Histone methylation is shown to epigenetically increase repressive transcription, altering lineage programming of mesenchymal stem cells (MSC). This study is undertaken to characterize the action of histone demethylase UTX to osteogenic lineage specification of bone-marrow MSC and bone integrity upon glucocorticoid treatment. Bone-marrow MSC were incubated in osteogenic medium containing supraphysiological dexamethasone. Osteogenic gene expression and mineralized nodule formation were probed using RT-PCR and von Kossa staining. The enrichment of trimethylated lysine 27 at histone 3 (H3K27me3) in Dkk1 promoter was quantified using chromatin immunoprecipitation-PCR. Bone mass and trabecular morphometry in methylprednisolone-treated skeletons were quantified using microCT analysis. Supraphysiological dexamethasone decreased osteogenic genes Runx2 and osteocalcin expression and mineralized matrix production along with reduced UTX expression in MSC. Forced UTX expression attenuated the glucocorticoid-mediated loss of osteogenic differentiation, whereas UTX knockdown provoked osteogenesis loss and cytoplasmic oil overproduction. UTX demethylated H3K27 and reduced the glucocorticoid-mediated the H3K27 enrichment in Dkk1 promoter, reversing beta-catenin signal, but downregulating Dkk1 production by MSC. In vivo, treatment with UTX inhibitor GSK-J4 significantly suppressed bone mineral density, trabecular volume, and thickness along with porous trabecular, fatty marrow and disturbed beta-catenin/Dkk1 histopathology comparable with glucocorticoid-induced osteoporosis condition. This study offers a productive insight into how UTX protects MSC from methylated histone-mediated osteogenesis repression in the development of glucocorticoid-induced osteoporosis


Bone & Joint Research
Vol. 10, Issue 12 | Pages 820 - 829
15 Dec 2021
Schmidutz F Schopf C Yan SG Ahrend M Ihle C Sprecher C

Aims. The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). Methods. A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability. Results. The CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92). Conclusion. The cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening. Cite this article: Bone Joint Res 2021;10(12):820–829


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 28 - 28
1 Nov 2021
Avnet S Lipreri MV Pompo GD Graziani G Boanini E Baldini N
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Introduction and Objective. The osteocyte, recognized as a major orchestrator of osteoblast and osteoclast activity, is the most important key player during bone remodeling processes. Imbalances that occur during bone remodeling, caused by hormone perturbations or alterations in mechanical loading, can induce bone disease as osteoporosis. Due to limited understanding of the underlying mechanisms, current therapies for osteoporosis cannot adequately address this imbalance because current studies of osteocytes rely on conventional cell culture that cannot recapitulate local in vivo microenvironments for the lack of control of the spatial/temporal distribution of cells and biomolecules. Microfluidics is the science and technology of microscale fluid manipulating and sensing and can help fill this gap. Materials and Methods. We used a microfluidic device to enable the culture of osteocyte-like cells (MLO-Y4 and MLO-A5) in a 3D fashion. Osteocytes were cultured in a perfused and 160 μm high channel and embedded in a bone-like extracellular matrix: osteocytes were embedded in a matrigel- and collagen-based hydrogel enriched with nanostructured hydroxypatite crystals (HA-NP) to mimic bone. To set up the best combination of matrigel enriched with Type I collagen we used fluorescent microspheres and confocal analysis. To evaluate the viability and the expression of osteocytic markers, we used live-dead assay amd immunofluorescent staining and confocal analysis combined with automated quantification. For mineralization, we performed alizarin red staining. Results. Osteocytes in the organ-on-a-chip model showed high viability and, in respect to 2D conventional cell cultures an increased differentiation, as assessed by a live-dead assay and the staining of the osteocytic markers connexin-43 and alkaline phosphatase and the increased mineralization activity. Furthermore, the addition of HA-NP significantly increased the formation of dendrite-like structures spreading through the xyz-axes, as assessed after G-actin immunofluorescence. Conclusions. Using a microfluidic device for MLO-Y4 and MLO-A5 cell cultures, compared to the 2D surfaces, we demonstrated a significant difference in cell differentiation and morphology. In particular, 3D cultures allowed the formation of 3D cell networks and the osteogenic phenotype. As a platform technology, this microfluidic device can function as a novel cell culture model that enables further studies of osteocytes and 3D co-culturing with other bone cells for the screening of anti-osteoporotic drugs


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 86 - 86
2 Jan 2024
Balmayor E Joris V van Griensven M
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Bone tissue is known to possess an intrinsic regeneration potential. However, in cases of major injury, trauma, and disease, bone loss is present, and the regeneration potential of the tissue is often impaired. The process of bone regeneration relies on a complex interaction of molecules. MicroRNAs (miRNA) are small, non-coding RNAs that inhibit messenger RNAs (mRNA). One miRNA can inhibit several mRNAs and one mRNA can be inhibited by several miRNAs. Functionally, miRNAs regulate the entire proteome via the local inhibition of translation. In fact, miRNA modulation has been shown to be involved in several musculoskeletal diseases. 1. In those pathologies, they modulate the transcriptional activity of mRNAs important for differentiation, tissue-specific activity, extracellular matrix production, etc. Because of their function in inhibiting translation, miRNAs are being researched in many diseases and are already being used for interventional treatment. 2. Bone tissue and its related conditions have been widely investigated up to this day. 1,3. This talk will focus on the relevancy of miRNAs to bone tissue, its homeostasis, and disease. After, examples will be given of how miRNAs can be used in bone regeneration and diseases such as osteoporosis and osteosarcoma. The use of miRNAs in both, detection and therapy will be discussed


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 64 - 64
11 Apr 2023
Steijvers E Xia Z Deganello D
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Accidents, osteoporosis or cancer can cause severe bone damage requiring grafts to heal. All current grafting methods have disadvantages including scarcity and infection/rejection risks. An alternative is therefore needed. Hydroxyapatite/calcium carbonate (HA/CC) scaffolds mimic the mineral bone composition but lack growth factors present in auto- and allografts, limiting their osteoinductive capacity. We hypothesize that this will increase the osteogenicity and osteoinductivity of scaffolds through the presence of growth factors. The objectives of this study are to develop and mass-produce grafts with enhanced osteoinductive capacity. HA/CC scaffolds were cultured together with umbilical cord mesenchymal stem cells in bioreactors so that they adhere to the surface and deposit growth factors. Cells growing on the scaffolds are confirmed by Alamar blue assays, SEM, and confocal microscopy. ELISA and IHC are used to assess the growth factor content of the finished product. It has been confirmed that cells attach to the scaffolds and proliferate over time when grown in bioreactors. Dynamic seeding of cells is clearly advantageous for cell deposits, equalizing the amount of cells on each scaffold granule. Hydroxyapatite/calcium carbonate scaffolds support cell-growth. This should be confirmed by further research, including Quantification of BMPs and other indicators of osteogenic differentiation such as Runx2, osteocalcin and ALP is pending, and amounts are expected to be increased in enhanced scaffolds and in-vivo implantation


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_14 | Pages 11 - 11
23 Jul 2024
Sarhan M Moreau J Francis S Page P
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Hip fractures frequently occur in elderly patients with osteoporosis and are rapidly increasing in prevalence owing to an increase in the elderly population and social activities. We experienced several recent presentations of TFNA nails failed through proximal locking aperture which requires significant revision surgery in often highly co-morbid patient population. The study was done by retrospective data collection from 2013 to 2023 of all the hip fractures which had been fixed with Cephalomedullary nails to review and compare Gamma (2013–2017) and TFNA (2017–2023) failure rates and the timing of the failures. Infected and Elective revision to Arthroplasty cases were excluded. The results are 1034 cases had been included, 784 fixed with TFNA and 250 cases fixed Gamma nails. Out of the 784 patients fixed with TFNA, 19 fixation failed (2.45%). Out of the 250 cases fixed with Gamma nails, 15 fixation failed (6%). Mean days for fixation failure were 323 and 244 days in TFNA and Gamma nails respectively. We conclude that TFNA showed remarkable less failure rates if compared to Gamma nails. At point of launch, testing was limited and no proof of superiority of TFNA over Gamma nail. Several failures identified with proximal locking aperture in TFNA which can be related to the new design which had Substantial reduction in lateral thickness at compression screw aperture


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 81 - 81
2 Jan 2024
van Griensven M
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Bone regeneration is pivotal for the healing of fractures. In case this process is disturbed a non-union can occur. This can be induced by environmental factors such as smoking, overloading etc. Co-morbidities such as diabetes, osteoporosis etc. may be more intrinsic factors besides other disturbances in the process. Those pathways negatively influence the bone regeneration process. Several intrinsic signal transduction pathways (WNT, BMP etc.) can be affected. Furthermore, on the transcriptional level, important mRNA expression can be obstructed by deregulated miRNA levels. For instance, several miRNAs have been shown to be upregulated during osteoporotic fractures. They are detrimental for osteogenesis as they block bone formation and accelerate bone resorption. Modulating those miRNAs may revert the physiological homeostasis. Indeed, physiological fracture healing has a typical miRNA signature. Besides using molecular pathways for possible treatment of non-union fractures, providing osteogenic cells is another solution. In 5 clinical cases with non-union fractures with defects larger than 10 cm, successful administration of a 3D printed PCL-TCP scaffold with autologous bone marrow aspirate concentrate and a modulator of the pathogenetic pathway has been achieved. All patients recovered well and showed a complete union of their fractures within one year after start of the regenerative treatment. Thus, non-union fractures are a diverse entity. Nevertheless, there seem to be common pathogenetic disturbances. Those can be counteracted at several levels from molecular to cell. Compositions of those may be the best option for future therapies. They can also be used in a more personalized fashion in case more specific measurements such as miRNA signature and stem cell activity are applied


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 52 - 52
7 Nov 2023
Mkhize S Masters J
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One of the most important sequelae to ageing is osteoporosis and subsequently hip fractures. Hip fractures are associated with major morbidity, mortality and costs. Most patients require surgery to restore mobility. Provision of surgery and its complications is poorly understood in South Africa. Our aim was to collect and report current hip fracture care at four centres in South Africa, as well as reporting surgical and general patient outcomes. A three year retrospective cohort at four centres will be described, focussing on provision of surgical care, mortality, types of surgery and complications. We identified 562 patients who had surgical intervention for fragility fractures, 66% were females. Forty nine percent had open reduction and internal fixation, 28% had hemi-arthroplasty replacement whilst 23% had total hip replacements. Twenty percent of patients had operative intervention within 36 hours of presentation to the emergency department. Mortality was 9% at 30 days. The most common complications were lower respiratory infections (29%), urinary tract infections (21%) and surgical site infections (9%). This is the largest cohort of surgically treated hip fracture from South Africa. Proportions of patients receiving different surgical interventions such as THR are comparable to the broader literature. However a number of key performance indicators such as surgery within 36 hours are challenging to meet. Given the changing demographics of South Africa, this study provides an early insight to contemporary care and may help provide direction for broader national strategies for reporting and improving hip fracture care


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 110 - 110
4 Apr 2023
Ding Y Li S Li C Chen Z Wu C
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Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening. Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival. In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed. Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 69 - 69
10 Feb 2023
Tong Y Holmes S Sefton1 A
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There is conjecture on the optimal timing to administer bisphosphonate therapy following operative fixation of low- trauma hip fractures. Factors include recommendations for early opportunistic commencement of osteoporosis treatment, and clinician concern regarding the effect of bisphosphonates on fracture healing. We performed a systematic review and meta-analysis to determine if early administration of bisphosphonate therapy within the first month post-operatively following proximal femur fracture fixation is associated with delay in fracture healing or rates of delayed or non-union. We included randomised controlled trials examining fracture healing and union rates in adults with proximal femoral fractures undergoing osteosynthesis fixation methods and administered bisphosphonates within one month of operation with a control group. Data was pooled in meta-analyses where possible. The Cochrane Risk of Bias Tool and the GRADE approach were used to assess validity. For the outcome of time to fracture union, meta-analysis of three studies (n= 233) found evidence for earlier average time to union for patients receiving early bisphosphonate intervention (MD = −1.06 weeks, 95% CI −2.01 – −0.12, I. 2. = 8%). There was no evidence from two included studies comprising 718 patients of any difference in rates of delayed union (RR 0.61, 95% CI 0.25–1.46). Meta-analyses did not demonstrate a difference in outcomes of mortality, function, or pain. We provide low-level evidence that there is no reduction in time to healing or delay in bony union for patients receiving bisphosphonates within one month of proximal femur fixation


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 70 - 70
11 Apr 2023
Domingues I Cunha R Domingues L Silva E Carvalho S Lavareda G Carvalho R
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Renal Osteodystrophy is a type of metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities. Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. Treatment involves medical management to resolve the etiology of the underlying renal condition, as well as management (and prevention) of pathological fractures. A 66-year-old female patient, with severe osteoporosis and chronic kidney disease undergoing haemodialysis, has presented with multiple fractures along the years. She was submitted to bilateral proximal femoral nailing as fracture treatment on the left and prophylactically due to pathological bone injury on the right, followed by revision of the left nail with a longer one after varus angulation and fracture distal to the nail extremity. Meanwhile, the patient suffered a pathological fracture of the radial and cubital diaphysis and was submitted to conservative treatment with cast, with consolidation of the fracture. Posteriorly, she re-fractured these bones after a fall and repeated the conservative treatment. Clinical management: There is a multidisciplinary approach to manage the chronic illness of the patient, including medical management to resolve the etiology and consequences of her chronic kidney disease, pain control, conservative or surgical fracture management and prevention of falls. The incidence of chronic renal disease is increasing and the patients with this condition live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Their quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. A multidisciplinary approach is required to treat these patients, controlling their chronic diseases, managing fractures and preventing falls


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_4 | Pages 5 - 5
8 Feb 2024
Ablett AD McCann C Feng T Macaskill V Oliver WM Keating JF
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This study compares outcomes of fixation of subtrochanteric femoral fractures using a single lag screw (Gamma3 nail, GN) with a dual lag screw device (InterTAN nail, IN). The primary outcome was mechanical failure, defined as lag screw cut-out, back-out, nail breakage or peri-implant fracture. Technical factors associated with mechanical failure were also identified. All adult patients (>18yrs) with a subtrochanteric femoral fracture treated in a single centre were retrospectively identified using electronic records. Included patients underwent surgical fixation using either a long GN (2010–2017) or IN (2017–2022). Cox regression analysis was used to determine the risk of mechanical failure and technical predictors of failure. The study included 587 patients, 336 in the GN group (median age 82yrs, 73% female) and 251 in the IN group (median age 82yrs, 71% female). The IN group exhibited a higher prevalence of osteoporosis (p=0.002) and CKD□3 (p=0.007). There were no other baseline differences between groups. The risk of any mechanical failure was increased two-fold in the GN group (HR 2.51, p=0.020). Mechanical failure comprising screw cut-out (p=0.040), back-out (p=0.040) and nail breakage (p=0.51) was only observed in the GN group. The risk of peri-implant fracture was similar between the groups (HR 1.10, p=0.84). Technical predictors of mechanical included varus >5° for cut-out (HR 15.61, p=0.016), TAD>25mm for back-out (HR 9.41, p=0.020) and shortening >1cm for peri-implant fracture (HR 6.50, p=<0.001). Dual lag screw designs may reduce the risk of mechanical complications for patients with subtrochanteric femoral fractures


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 72 - 72
17 Apr 2023
Hsieh Y Hsieh M Shu Y Lee H
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A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer. We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body. The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone. In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed. In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation. The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_12 | Pages 73 - 73
23 Jun 2023
Sheth N Bostrom M Winzenrieth R Humbert L Pearman L Caminis J Wang Y Boxberger J Krohn K
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To evaluate the effects of 6 and 18 months of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP). Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fractures. a. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups. c. ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture. Effects of ABL on acetabular BMD are unknown. Hip DXA scans were obtained at baseline, 6, and 18 months from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group). Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical P values were based on a repeated mixed measures model. BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 months compared with PBO (all P<0.0001 vs PBO). BMD in the PBO group was relatively stable over time. ABL treatment resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. In bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 6 - 6
11 Apr 2023
Kronenberg D Everding J Wendler L Brand M Timmen M Stange R
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Integrin α2β1 is one of the major transmembrane receptors for fibrillary collagen. In native bone we could show that the absence of this protein led to a protective effect against age-related osteoporosis. The objective of this study was to elucidate the effects of integrin α2β1 deficiency on fracture repair and its underlying mechanisms. Standardised femoral fractures were stabilised by an intramedullary nail in 12 week old female C57Bl/6J mice (wild type and integrin α2. -/-. ). After 7, 14 and 28 days mice were sacrificed. Dissected femura were subjected to µCT and histological analyses. To evaluate the biomechanical properties, 28-day-healed femura were tested in a torsional testing device. Masson goldner staining, Alizarin blue, IHC and IF staining were performed on paraffin slices. Blood serum of the animals were measured by ELISA for BMP-2. Primary osteoblasts were analysed by in/on-cell western technology and qRT-PCR. Integrin α2β1 deficient animals showed earlier transition from cartilaginous callus to mineralized callus during fracture repair. The shift from chondrocytes over hypertrophic chondrocytes to bone-forming osteoblasts was accelerated. Collagen production was increased in mutant fracture callus. Serum levels of BMP-2 were increased in healing KO mice. Isolated integrin deficient osteoblast presented an earlier expression and production of active BMP-2 during the differentiation, which led to earlier mineralisation. Biomechanical testing showed no differences between wild-type and mutant bones. Knockout of integrin α2β1 leads to a beneficial outcome for fracture repair. Callus maturation is accelerated, leading to faster recovery, accompanied by an increased generation of extra-cellular matrix material. Biomechanical properties are not diminished by this accelerated healing. The underlying mechanism is driven by an earlier availability of BMP-2, one main effectors for bone development. Local inhibition of integrin α2β1 is therefore a promising target to accelerate fracture repair, especially in patients with retarded healing


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 92 - 92
17 Apr 2023
Raina D Mrkonjic F Tägil M Lidgren L
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A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones. Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups. CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material. We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 66 - 66
4 Apr 2023
Li M Chow S Wong R Cheung W
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Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation. Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin. DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 & 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process. The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing. Acknowledgment: General Research Fund (Ref: 14113018)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 87 - 87
2 Jan 2024
Moura S Olesen J Barbosa M Soe K Almeida M
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Osteoclasts (OCs) are multinucleated cells that play a pivotal role in skeletal development and bone remodeling. Abnormal activation of OCs contributes to the development of bone-related diseases, such as osteoporosis, bone metastasis and osteoarthritis. Restoring the normal function of OCs is crucial for bone homeostasis. Recently, RNA therapeutics emerged as a new field of research for osteoarticular diseases. The aim of this study is to use non-coding RNAs (ncRNAs) to molecularly engineer OCs and modulate their function. Specifically, we investigated the role of the microRNAs (namely miR-16) and long ncRNAs (namely DLEU1) in OCs differentiation and fusion. DLEU1/DLEU2 region, located at chromosome 13q14, also encodes miR-15 and miR-16. Our results show that levels of these ncRNA transcripts are differently expressed at distinct stages of the OCs differentiation. Specifically, silencing of DLEU1 by small interfering RNAs (siDLEU1) and overexpression of miR-16 by synthetic miRNA mimics (miR-16-mimics) led to a significant reduction in the number of OCs formed per field (OC/field), both at day 5 and 9 of the differentiation stage. Importantly, time-lapse analysis, used to track OCs behavior, revealed a significant decrease in fusion events after transfection with siDLEU1 or miR-16-mimics and an alteration in the fusion mode and partners. Next, we investigated the migration profile of these OCs, and the results show that only miR-16-mimics-OCs, but not siDLEU-OCs, have a lower percentage of immobile cells and an increase in cells with mobile regime, compared with controls. No differences in cell shape were found. Moreover, mass-spectrometry quantitative proteomic analysis revealed independent effects of siDLEU1 and miR-16-mimics at the protein levels. Importantly, DLEU1 and miR-16 act by distinct processes and pathways. Collectively, our findings support the ncRNAs DLEU1 and miR-16 as therapeutic targets to modulate early stages of OCs differentiation and, consequently, to impair OC fusion, advancing ncRNA-therapeutics for bone-related diseases. Acknowledgements: Authors would like to thank to AO CMF / AO Foundation (AOCMFS-21-23A). SRM and MIA are supported by FCT (SFRH/BD/147229/2019 and BiotechHealth Program; CEECINST/00091/2018/CP1500/CT0011, respectively)


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 38 - 38
17 Apr 2023
Saiz A Hideshima K Haffner M Rice M Goupil J VanderVoort W Delman C Hallare J Choi J Shieh A Eastman J Wise B Lee M
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Determine the prevalence, etiologies, and risk factors of unplanned return to the OR (UROR) in adult orthopaedic trauma patients. Retrospective review of a trauma prospective registry from 2014 – 2019 at a Level 1 academic hospital. An UROR was defined as a patient returning to OR unexpectedly following a planned definitive surgery to either readdress the presenting diagnosis or address a complication arising from the index procedure. Univariate and multivariate logistic regression was performed comparing those patients with an UROR versus those without. A total of 1568 patients were reviewed. The rate of UROR was 9.8% (153 patients). Symptomatic implant was the leading cause of UROR (60%). Other significant UROR causes were infection (15%) and implant failure (9%). The median time between index procedure and UROR was 301 days. For the univariate and multivariate analysis, open fracture (p< 0.05), fracture complexity (p<0.01), and weekend procedure (p< 0.01) were all associated with increased risk of UROR. All other variables were not statistically significant for any associations. Those patients with an UROR for reasons other than symptomatic implants were more likely to have polyorthopaedic injuries (p < 0.05), ISS > 15 (p < 0.05), osteoporosis (p < 0.01), ICU status (p < 0.05), psychiatric history (p < 0.05), compartment syndrome (p < 0.05), neurovascular injury (p < 0.01), open fracture (p < 0.05), and fracture complexity (p < 0.05). The rate of UROR in the orthopaedic trauma patient population is 10%. Most of these cases are due to implant-related issues. UROR for reasons other than symptomatic implants tend to be polytraumatized patients with higher-energy injuries, multiple complex fractures, and associated soft tissue injuries. Future focus on improved implant development and treatments for polytraumatized patients with complex fractures is warranted to decrease a relatively high UROR rate in orthopaedic trauma


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_13 | Pages 2 - 2
17 Jun 2024
Fishley W Morrison R Baldock T Hilley A Baker P Townshend D
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Background. In fixation of the fibula in ankle fractures, AO advocate using a lag screw and one-third tubular neutralisation plate for simple patterns. Where a lag screw cannot be placed, bridging fixation is required. A local pilot service evaluation previously identified variance in use of locking plates in all patterns with significant cost implications. The FAIR study aimed to evaluate current practice and implant use across the United Kingdom (UK) and review outcomes and complication rates between different fibula fixation methods. Method. The study was supported by CORNET, the North East trainee research collaborative, and BOTA. Data was collected using REDCap from 22 centres in the UK retrospectively for a one-year period between 1. st. January 2019 and 31. st. December 2019 on injury mechanism, fracture characteristics, comorbidities, fixation and complications. Follow-up data was collected to at least two-years from the time surgery. Results. 1448 ankle fractures which involved fixation of the fibula were recorded; one-third tubular plate was used in 866 (59.8%) cases, a locking plate in 463 (32.0%) cases and other methods in 119 (8.2%) cases. There was significant difference between centres (p<0.001) in implant type used. Other factors associated with implant type were age, diabetes, osteoporosis, open fractures, fracture pattern and the presence of comminution. Incidence of lateral wound breakdown was higher in locking plates than one-third tubular plates (p<0.05). There was no significant difference in infection, non-union, fixation failure or removal of metalware. Conclusion. There is significant variation in practice in the UK in implant use for fixation of the fibula in ankle fractures. Potentially unnecessary use of locking plates, where a one-third tubular shows equivalent outcomes, incurs additional cost and may increase the risk of lateral wound breakdown. We would encourage surgeons with high locking plate usage to evaluate their own unit's practice against this data


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 133 - 133
2 Jan 2024
Carvalho M Cabral J da Silva C
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Mesenchymal stromal cells (MSC) have been proposed as an emerging cell therapy for bone tissue engineering applications. However, the healing capacity of the bone tissue is often compromised by patient's age and comorbidities, such as osteoporosis. In this context, it is important to understand the impact of donor age on the therapeutic potential of MSC. Importantly, the impact on donor age is not restricted to cells themselves but also to their microenvironment that is known to affect cell function. The extracellular matrix (ECM) has an important role in stem cell microenvironment, being able to modulate cell proliferation, self-renewal and differentiation. Decellularized cell-derived ECM (dECM) has been explored for regenerative medicine applications due to its bioactivity and its resemblance to the in vivo microenvironment. Thus, dECM offers the opportunity not only to develop microenvironments with customizable properties for improvement of cellular functions but also as a platform to study cellular niches in health and disease. In this study, we investigated the capacity of the microenvironment to rescue the impaired proliferative and osteogenic potential of aged MSC. The goal of this work was to understand if the osteogenic capacity of MSC could be modulated by exposure to a dECM derived from cells obtained from young donors. When aged MSC were cultured on dECM derived from young MSC, their in vitro proliferative and osteogenic capacities were enhanced. Our results suggest that the microenvironment, specifically the ECM, plays a crucial role in the osteogenic differentiation capacity of MSC. dECM might be a valuable clinical strategy to overcome the age-related decline in the osteogenic potential of MSC by recapitulating a younger microenvironment, attenuating the effects of aging on the stem cell niche. Overall, this study opens new possibilities for developing clinical strategies for elderly patients with limited bone formation capacity who currently lack effective treatments. Acknowledgements: The authors thank FCT for funding through the project DentalBioMatrix (PTDC/BTM-MAT/3538/2020) and to the research institutions iBB (UIDB/04565/2020 and UIDP/04565/2020) and Associate Laboratory i4HB (LA/P/0140/2020)


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 138 - 138
1 Apr 2019
Watanabe Y Yamamoto S Isawa K Yamada N Hirota Y
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Background. Recently, a larger number of elderly individuals with osteoporosis has undergone total knee arthroplasty (TKA). Intuitively, such vulnerable bone condition should deteriorate post-TKA functional recovery compared to a non-osteoporotic condition, but this hypothesis has not been directly examined. Methods. To address this issue, we analysed prognosis of patients who underwent TKA in Toranomon Hospital in Japan between April 2016 and March 2017 (27 of 40 cases, age 75.0±8.2 years old, BMI 24.5±3.1), and evaluated effects of osteoporosis on the changes in functions of the knees three/six/twelve months after the operation. The knee functions were quantified based on Knee Society Score (KSS), and the severity of the pre-operative osteoporosis was evaluated by T-score. We examined the relationships between these scores using multiple regression analyses with age, BMI, and sex as covariates. We excluded patients with rheumatoid arthritis. Results. The multiple regression analyses revealed that the severity of osteoporosis (T-score) before TKA did not have sufficient explanatory powers for either type of KSS (for Knee Score, adjusted R2 ≤ 0.16; for Functional Score, adjusted R2 ≤ 0.15). In addition, Pearson correlation coefficients between the pre-operative osteoporosis severity and KSS were weak (for Knee Score, |r| < 0.07, P > 0.78; for Functional Score, |r| < 0.27, P > 0.21; Fig 1). This tendency was qualitatively preserved even when we repeated these analyses for each sex group. Conclusions. These analyses suggest that counterintuitively, pre-operative osteoporosis does not significantly deteriorate the functional outcome of TKA in the elderly population. Although longer observations of larger samples will be needed, the current findings indicate the possibility that we may not have to hesitate over TKA even for osteoporotic patients. For any figures or tables, please contact the authors directly


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 128 - 128
11 Apr 2023
Elbahi A Onazi O Ramadan M Hanif Y Eastley N Houghton-Clemmey R
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It is known that Osteoporosis is the pathology of bone mass and tissue loss resulting in an increase of fragility, risk of fracture occurrence, and risk of fracture recurrence. We noted there was no definitive pathway in our last audit, therefore recommended: availability of the Osteoporosis clinic referral form in an accessible place, the form be filled by the doctor reviewing the patient in the first fracture clinic, and a liaison nurse to ensure these forms were filled and sent to the Osteoporosis clinic. This second audit analyses our Trust's response to these recommendations and effect achieved in Osteoporosis care. We reviewed our local data base from the 7/27/2020 – 10/2/2021 retrospectively for distal radius fractures who were seen in fracture clinic. We analysed a sample size of 59 patients, excluding patients who had already commenced bone protection medications. 67.7% of our patients had neither been on bone protection medications nor recorded referrals and 13.5% were already on bone protection medications when they sustained the fragility fracture. Ten out of the 51 patients were offered referral to the osteoporosis clinic, and one refused. This makes 20% (10 out of 50) of the patients had completed referrals. In comparison, in our first audit, 11% had already been on bone protection medications and 18% had completed referrals. The second cycle showed a slight increase in compliance. Majority of the referrals were completed by Orthopaedic Consultants in both audits and ana awareness increase noted among non-consultants in starting the referral process. Based on our analysis, our Trust has a slight improvement in commencing bone protection medications, associated with slight improvement in completing referrals to the Osteoporosis clinic. Despite our recommendations in the first audit, there is still no easily accessible definitive pathway to ensure our Trust's patients have timely access to bone protection and continued care at the Osteoporosis clinic. We recommend streamlining our recommendations to have a more effective approach in ensuring our Trust meets national guidelines. We will implement a Yes or No question assessment for patients visiting clinic in our electronic database which should assist in referral completions


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 72 - 72
11 Apr 2023
Stich T Kovářík T Křenek T Alt V Docheva D
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The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts. The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification. Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold). The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 6 - 6
17 Nov 2023
Luo J Lee R
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Abstract. Objectives. The aim of this study was to investigate whether mechanical loading induced by physical activity can reduce risk of sarcopenia in middle-aged adults. Methods. This was a longitudinal study based on a subset of UK Biobank data consisting of 1,918 participants (902 men and 1,016 women, mean age 56 years) who had no sarcopenia at baseline (assessed between 2006 and 2010). The participants were assessed again after 6 years at follow-up, and were categorized into no sarcopenia, probable sarcopenia, or sarcopenia according to the definition and algorithm developed in 2018 by European Working Group on Sarcopenia in Older People (EWGSOP). Physical activity was assessed at a time between baseline and follow-up using 7-day acceleration data obtained from wrist worn accelerometers. Raw acceleration data were then analysed to study the mechanical loading of physical activity at different intensities (i.e. very light, light, moderate-to-vigorous). Multinominal logistic regression was employed to examine the association between the incidence of sarcopenia and physical activity loading, between baseline and follow up, controlled for other factors at baseline including age, gender, BMI, smoking status, intake of alcohol, vitamin D and calcium, history of rheumatoid arthritis, osteoarthritis, secondary osteoporosis, and type 2 diabetes. Results. Among the 1918 participants with no sarcopenia at baseline, 230 (69 men and 161 women) developed probable sarcopenia and 37 (14 men and 23 women) developed sarcopenia at follow-up. Physical activity loading at moderate-to-vigorous intensity was higher in men (p<0.05), while women had higher physical activity loading at very light intensity (p<0.05). No significant difference was found in physical activity loading at light intensity between men and women (p>0.05). Logistic regression models showed that increase in physical activity loading at moderate-to-vigorous intensity significantly reduced the risk of sarcopenia (odds ratio = 0.368, p<0.05), but not probable sarcopenia (odds ratio = 0.974, p>0.05), while loading at light or very light activity intensity were not associated with the risk of sarcopenia or probable sarcopenia (p>0.05). Conclusion. Loading of physical activity at moderate-to-vigorous intensity could reduce risk of sarcopenia in middle-aged adults. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project