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Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 548 - 554
1 Jun 2024
Ohyama Y Minoda Y Masuda S Sugama R Ohta Y Nakamura H

Aims. The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). Methods. The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded. Results. There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone. Conclusion. The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes. Cite this article: Bone Joint J 2024;106-B(6):548–554


Bone & Joint Research
Vol. 13, Issue 4 | Pages 184 - 192
18 Apr 2024
Morita A Iida Y Inaba Y Tezuka T Kobayashi N Choe H Ike H Kawakami E

Aims. This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. Methods. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Results. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Conclusion. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss. Cite this article: Bone Joint Res 2024;13(4):184–192


Bone & Joint 360
Vol. 13, Issue 2 | Pages 26 - 29
1 Apr 2024

The April 2024 Wrist & Hand Roundup360 looks at: Lunocapitate versus four-corner fusion in scapholunate or scaphoid nonunion advanced collapse: a randomized controlled trial; Postoperative scaphoid alignment, smoking, and avascular necrosis determine outcomes; Grip strength signals broader health concerns in females with distal radius fractures; Clearing the smoke: how smoking status influences recovery from open carpal tunnel release surgery; Age matters: assessing the likelihood of corrective surgery after distal radius fractures; Is pronator quadratus muscle repair required after anterior plate fixation for distal radius fractures?; Efficacy of total wrist arthroplasty: a comparative analysis of inflammatory and non-inflammatory arthritis outcomes; A comprehensive review of the one-bone forearm as a salvage technique.


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.


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. 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.


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.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 580 - 589
20 Sep 2023
Dai X Liu B Hou Q Dai Q Wang D Xie B Sun Y Wang B

Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Methods

In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties.


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


The Bone & Joint Journal
Vol. 105-B, Issue 9 | Pages 993 - 999
1 Sep 2023
van Delft EAK van Bruggen SGJ van Stralen KJ Bloemers FW Sosef NL Schep NWL Vermeulen J

Aims

There is no level I evidence dealing with the optimal period of immobilization for patients with a displaced distal radial fracture following closed reduction. A shorter period might lead to a better functional outcome due to less stiffness and pain. The aim of this study was to investigate whether this period could be safely reduced from six to four weeks.

Methods

This multicentre randomized controlled trial (RCT) included adult patients with a displaced distal radial fracture, who were randomized to be treated with immobilization in a cast for four or six weeks following closed reduction. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) score after follow-up at one year. Secondary outcomes were the abbreviated version of the Disability of Arm, Shoulder and Hand (QuickDASH) score after one year, the functional outcome at six weeks, 12 weeks, and six months, range of motion (ROM), the level of pain after removal of the cast, and complications.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 504 - 511
23 Aug 2023
Wang C Liu S Chang C

Aims

This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model.

Methods

A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 612 - 620
21 Aug 2023
Martin J Johnson NA Shepherd J Dias J

Aims

There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method.

Methods

The most common anatomical variant of the scaphoid was modelled from a CT scan of a healthy hand and wrist using 3D Slicer freeware. This model was uploaded into COMSOL Multiphysics software to enable the application of physiological enhancements. Three common waist fracture patterns were produced following the Russe classification. Each fracture had differing stages of healing, ranging from 10% to 90% partial union, with increments of 10% union assessed. A physiological force of 100 N acting on the distal pole was applied, with the risk of refracture assessed using the Von Mises stress.


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.


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.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 723 - 728
1 Jul 2023
Raj RD Fontalis A Grandhi TSP Kim WJ Gabr A Haddad FS

There is a disparity in sport-related injuries between sexes, with females sustaining non-contact musculoskeletal injuries at a higher rate. Anterior cruciate ligament ruptures are between two and eight times more common than in males, and females also have a higher incidence of ankle sprains, patellofemoral pain, and bone stress injuries. The sequelae of such injuries can be devastating to an athlete, resulting in time out of sport, surgery, and the early onset of osteoarthritis. It is important to identify the causes of this disparity and introduce prevention programmes to reduce the incidence of these injuries. A natural difference reflects the effect of reproductive hormones in females, which have receptors in certain musculoskeletal tissues. Relaxin increases ligamentous laxity. Oestrogen decreases the synthesis of collagen and progesterone does the opposite. Insufficient diet and intensive training can lead to menstrual irregularities, which are common in female athletes and result in injury, whereas oral contraception may have a protective effect against certain injuries. It is important for coaches, physiotherapists, nutritionists, doctors, and athletes to be aware of these issues and to implement preventive measures. This annotation explores the relationship between the menstrual cycle and orthopaedic sports injuries in pre-menopausal females, and proposes recommendations to mitigate the risk of sustaining these injuries.

Cite this article: Bone Joint J 2023;105-B(7):723–728.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351


Bone & Joint Open
Vol. 4, Issue 5 | Pages 306 - 314
3 May 2023
Rilby K Mohaddes M Kärrholm J

Aims

Although the Fitmore Hip Stem has been on the market for almost 15 years, it is still not well documented in randomized controlled trials. This study compares the Fitmore stem with the CementLeSs (CLS) in several different clinical and radiological aspects. The hypothesis is that there will be no difference in outcome between stems.

Methods

In total, 44 patients with bilateral hip osteoarthritis were recruited from the outpatient clinic at a single tertiary orthopaedic centre. The patients were operated with bilateral one-stage total hip arthroplasty. The most painful hip was randomized to either Fitmore or CLS femoral component; the second hip was operated with the femoral component not used on the first side. Patients were evaluated at three and six months and at one, two, and five years postoperatively with patient-reported outcome measures, radiostereometric analysis, dual-energy X-ray absorptiometry, and conventional radiography. A total of 39 patients attended the follow-up visit at two years (primary outcome) and 35 patients at five years. The primary outcome was which hip the patient considered to have the best function at two years.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 568 - 574
1 May 2023
Kobayashi H Ito N Nakai Y Katoh H Okajima K Zhang L Tsuda Y Tanaka S

Aims

The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

Methods

The study included 33 patients with TIO who were treated between January 2000 and June 2022. The causative tumour was detected in all patients. We investigated the symptoms and evaluated the radiological patterns of insufficiency fractures of the rib, spine, and limbs.


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. 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. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154


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.


Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Methods

In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.


The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1132 - 1141
1 Oct 2022
Holm-Glad T Røkkum M Röhrl SM Roness S Godang K Reigstad O

Aims. To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour. Methods. A total of 40 patients suffering from non-rheumatoid wrist arthritis were enrolled in a randomized controlled trial comparing the ReMotion and Motec TWAs. Patient-rated and functional outcomes, radiological changes, blood metal ion levels, migration measured by model-based radiostereometric analysis (RSA), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), complications, loosening, and revision rates at two years were compared. Results. Patient-Rated Wrist and Hand Evaluation (PRWHE) scores, abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) scores, and pain improved similarly and significantly in both groups. Wrist motion improved significantly in the Motec group only, and forearm rotation in the ReMotion group only. Cobalt (Co) and chromium (Cr) blood ion levels were significantly higher in the metal-on-metal (MoM) Motec group than in the metal-on-polyethylene (MoP) ReMotion group. Mean total translation was 0.65 mm (95% confidence interval (CI) 0.26 to 1.12) and 0.27 mm (95% CI 0.14 to 0.47) for the ReMotion carpal and radial components, and 0.32 mm (95% CI 0.22 to 0.45) and 0.26 mm (95% CI 0.20 to 0.34) for the Motec metacarpal and radial components, respectively. Apart from dorsal and volar tilts, which were significantly higher for the radial ReMotion than for the Motec component, no significant differences in absolute migration occurred. BMD around the radial components never returned to baseline. Almost one-third of patients required reoperation due to complications. Two ReMotion implants were revised to Motec TWAs due to carpal component loosening, and three Motec MoM articulations were revised to metal-on-polyether ether ketone due to painful synovitis. Conclusion. Both implants provided matched function and were stable at short-term follow-up, but with a high complication rate. This procedure should be restricted to specialist centres undertaking prospective analysis until its role is clarified. Cite this article: Bone Joint J 2022;104-B(10):1132–1141


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Methods

Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 528 - 540
1 Aug 2022
Dong W Postlethwaite BC Wheller PA Brand D Jiao Y Li W Myers LK Gu W

Aims

This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Methods

A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 585 - 593
1 Aug 2022
Graham SM Jalal MMK Lalloo DG Hamish R. W. Simpson A

Aims

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Methods

A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 503 - 512
25 Jul 2022
Wu Y Shao Y Xie D Pan J Chen H Yao J Liang J Ke H Cai D Zeng C

Aims

To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

Methods

In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 465 - 476
13 Jul 2022
Li MCM Chow SK Wong RMY Chen B Cheng JCY Qin L Cheung W

Aims

There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV.

Methods

A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Methods

Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 439 - 452
13 Jul 2022
Sun Q Li G Liu D Xie W Xiao W Li Y Cai M

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 413 - 425
1 Jul 2022
Tu C Lai S Huang Z Cai G Zhao K Gao J Wu Z Zhong Z

Aims

Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism.

Methods

Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 386 - 397
22 Jun 2022
Zhu D Fang H Yu H Liu P Yang Q Luo P Zhang C Gao Y Chen Y

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Methods

MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.


Bone & Joint 360
Vol. 11, Issue 3 | Pages 5 - 8
1 Jun 2022
Rigney B


The Bone & Joint Journal
Vol. 104-B, Issue 6 | Pages 647 - 656
1 Jun 2022
Knudsen MB Thillemann JK Jørgensen PB Jakobsen SS Daugaard H Søballe K Stilling M

Aims

BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems.

Methods

A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery.


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


Aims. The aim of this study was to compare the mid-term patient-reported outcome, bone remodelling, and migration of a short stem (Collum Femoris Preserving; CFP) with a conventional uncemented stem (Corail). Methods. Of 81 patients who were initially enrolled, 71 were available at five years’ follow-up. The outcomes at two years have previously been reported. The primary outcome measure was the clinical result assessed using the Oxford Hip Score (OHS). Secondary outcomes were the migration of the stem, measured using radiostereometric analysis (RSA), change of bone mineral density (BMD) around the stem, the development of radiolucent lines, and additional patient-reported outcome measures (PROMs). Results. There were no statistically significant differences between the groups regarding PROMs (median OHS (CFP 45 (interquartile range (IQR) 35 to 48); Corail 45 (IQR 40 to 48); p = 0.568). RSA showed stable stems in both groups, with little or no further subsidence between two and five years. Resorption of the femoral neck was evident in nine patients in the CFP group and in none of the 15 Corail stems with a collar that could be studied. Dual X-ray absorbiometry showed a significantly higher loss of BMD in the proximal Gruen zones in the CFP group (mean changes in BMD: Gruen zone 1, CFP -9.5 (95% confidence interval (CI) -14.8 to -4.2), Corail 1.0 (95% CI 3.4 to 5.4); Gruen zone 7, CFP -23.0 (95% CI -29.4 to -16.6), Corail -7.2 (95% CI -15.9 to 1.4). Two CFP stems were revised before two years’ follow-up due to loosening, and one Corail stem was revised after two years due to chronic infection. Conclusion. The CFP stem has a similar clinical outcome and subsidence pattern when compared with the Corail stem. More pronounced proximal stress-shielding was seen with the CFP stem, suggesting diaphyseal fixation, and questioning its femoral neck-sparing properties in the long term. Cite this article: Bone Joint J 2022;104-B(5):581–588


Bone & Joint Research
Vol. 11, Issue 4 | Pages 229 - 238
11 Apr 2022
Jaeger S Eissler M Schwarze M Schonhoff M Kretzer JP Bitsch RG

Aims. One of the main causes of tibial revision surgery for total knee arthroplasty is aseptic loosening. Therefore, stable fixation between the tibial component and the cement, and between the tibial component and the bone, is essential. A factor that could influence the implant stability is the implant design, with its different variations. In an existing implant system, the tibial component was modified by adding cement pockets. The aim of this experimental in vitro study was to investigate whether additional cement pockets on the underside of the tibial component could improve implant stability. The relative motion between implant and bone, the maximum pull-out force, the tibial cement mantle, and a possible path from the bone marrow to the metal-cement interface were determined. Methods. A tibial component with (group S: Attune S+) and without (group A: Attune) additional cement pockets was implanted in 15 fresh-frozen human leg pairs. The relative motion was determined under dynamic loading (extension-flexion 20° to 50°, load-level 1,200 to 2,100 N) with subsequent determination of the maximum pull-out force. In addition, the cement mantle was analyzed radiologically for possible defects, the tibia base cement adhesion, and preoperative bone mineral density (BMD). Results. The BMD showed no statistically significant difference between both groups. Group A showed for all load levels significantly higher maximum relative motion compared to group S for 20° and 50° flexion. Group S improved the maximum failure load significantly compared to group A without additional cement pockets. Group S showed a significantly increased cement adhesion compared to group A. The cement penetration and cement mantle defect analysis showed no significant differences between both groups. Conclusion. From a biomechanical point of view, the additional cement pockets of the component have improved the fixation performance of the implant. Cite this article: Bone Joint Res 2022;11(4):229–238


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.


Bone & Joint Open
Vol. 3, Issue 3 | Pages 261 - 267
22 Mar 2022
Abe S Kashii M Shimada T Suzuki K Nishimoto S Nakagawa R Horiki M Yasui Y Namba J Kuriyama K

Aims. Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. Methods. This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared. Results. The articular comminuted group (n = 28) had a significantly lower median serum 25-hydroxyvitamin-D level than the non-comminuted group (n = 94; 13.4 ng/ml (interquartile range (IQR) 9.8 to 17.3) vs 16.2 ng/ml (IQR 12.5 to 20.4); p = 0.005). The AO classification and volar cortex comminution were not correlated with the serum 25-hydroxyvitamin-D level. Bone metabolic markers and BMD did not significantly differ in terms of DRF severities. Conclusion. Articular comminuted DRF, referred to as AO C3 fracture, is significantly associated with low serum 25-hydroxyvitamin-D levels. Therefore, vitamin D. 3. supplementation for vitamin D deficiency might prevent articular comminuted DRFs. Nevertheless, further studies must be conducted to validate the results of the current study. Cite this article: Bone Jt Open 2022;3(3):261–267


Bone & Joint Research
Vol. 11, Issue 2 | Pages 82 - 90
7 Feb 2022
Eckert JA Bitsch RG Sonntag R Reiner T Schwarze M Jaeger S

Aims

The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation.

Methods

Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora. We generated 5° bone defects at the posterior condyle. Relative movement was simulated using a servohydraulic pulser, and analyzed at 70°/115° knee flexion. Relative movement was surveyed at seven points of measurement on implant and bone, using an optic system.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 49 - 60
1 Feb 2022
Li J Wong RMY Chung YL Leung SSY Chow SK Ip M Cheung W

Aims

With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

Methods

A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 104 colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 840 - 843
15 Dec 2021
Al-Hourani K Tsang SJ Simpson AHRW


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


Bone & Joint Research
Vol. 10, Issue 12 | Pages 830 - 839
15 Dec 2021
Robertson G Wallace R Simpson AHRW Dawson SP

Aims. Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning. Methods. A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading. Results. Cortical measures showed varying correlations with the forearm DXA results (range: Pearson correlation coefficient (r) = 0.343 (p = 0.251) to r = 0.521 (p = 0.068)), with none showing statistically significant correlations. Aluminium equivalent grading showed statistically significant correlations with the forearm DXA of the corresponding region of interest (p < 0.017). Conclusion. Cortical measures, cortical indices, and combined cortical scores did not show a statistically significant correlation to forearm DXA measures. Aluminium-equivalent is an easily applicable method for estimation of BMD from digital radiographs in the preoperative setting. Cite this article: Bone Joint Res 2021;10(12):830–839


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

Methods

The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.


Bone & Joint 360
Vol. 10, Issue 6 | Pages 33 - 35
1 Dec 2021


Bone & Joint 360
Vol. 10, Issue 6 | Pages 45 - 46
1 Dec 2021


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1648 - 1655
1 Nov 2021
Jeong S Hwang K Oh C Kim J Sohn OJ Kim JW Cho Y Park KC

Aims

The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years.

Methods

From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 734 - 741
1 Nov 2021
Cheng B Wen Y Yang X Cheng S Liu L Chu X Ye J Liang C Yao Y Jia Y Zhang F

Aims. Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. Methods. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively. Results. We detected five, three, and seven candidate gut microbiota-related traits for L1-L4 BMD, total BMD, and femur BMD, respectively, such as genus Dialister (p = 0.004) for L1-L4 BMD, and genus Eisenbergiella (p = 0.046) for total BMD. We also detected two common gut microbiota-related traits shared by L1-L4 BMD, total BMD, and femur total BMD, including genus Escherichia Shigella and genus Lactococcus. Interaction analysis of BMD detected several genes that interacted with gut microbiota, such as phospholipase D1 (PLD1) and endomucin (EMCN) interacting with genus Dialister in total BMD, and COL12A1 and Discs Large MAGUK Scaffold Protein 2 (DLG2) interacting with genus Lactococcus in femur BMD. Conclusion. Our results suggest associations between gut microbiota and BMD, which will be helpful to further explore the regulation mechanism and intervention gut microbiota of BMD. Cite this article: Bone Joint Res 2021;10(11):734–741


Bone & Joint 360
Vol. 10, Issue 5 | Pages 4 - 5
1 Oct 2021
Graham SM Harrison WJ Laubscher M Maqungo S


Bone & Joint Research
Vol. 10, Issue 10 | Pages 659 - 667
1 Oct 2021
Osagie-Clouard L Meeson R Sanghani-Kerai A Bostrom M Briggs T Blunn G

Aims

A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

Methods

A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1497 - 1504
1 Sep 2021
Rotman D Ariel G Rojas Lievano J Schermann H Trabelsi N Salai M Yosibash Z Sternheim A

Aims

Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients.

Methods

A retrospective cohort study was undertaken using autonomous CTFEA performed on existing abdominal or pelvic CT data comparing two groups of T2DM patients: a study group of 27 patients who had sustained a hip fracture within the year following the CT scan and a control group of 24 patients who did not have a hip fracture within one year. The main outcome of the CTFEA is a novel measure of hip bone strength termed the Hip Strength Score (HSS).


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 73 - 77
1 Jul 2021
Lawrie CM Barrack RL Nunley RM

Aims. Dual mobility (DM) implants have been shown to reduce the dislocation rate after total hip arthroplasty (THA), but there remain concerns about the use of cobalt chrome liners inserted into titanium shells. The aim of this study was to assess the clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) at mid-term follow-up in young, active patients receiving a modular DM THA. Methods. This was a prospective study involving patients aged < 65 years, with a BMI of < 35 kg/m. 2. , and University of California, Los Angeles activity score of > 6 who underwent primary THA with a modular cobalt chrome acetabular liner, highly cross-linked polyethylene mobile bearing, and a cementless titanium femoral stem. Patient-reported outcome measures, whole blood metal ion levels (μg/l), and periprosthetic femoral BMD were measured at baseline and at one, two, and five years postoperatively. The results two years postoperatively for this cohort have been previously reported. Results. A total of 43 patients were enrolled. At minimum follow-up of five years, 23 (53.4%) returned for clinical and radiological review, 25 (58.1%) had metal ion analysis performed, 19 (44.2%) underwent dual energy x-ray absorptiometry scans, and 25 (58%) completed a pain-drawing questionnaire. The mean modified Harris Hip Scores improved significantly from 54.8 (SD 19) preoperatively to 93.08 (SD 10.5) five years postoperatively (p < 0.001). One patient was revised for aseptic acetabular loosening. The mean cobalt levels increased from 0.065 μg/l (SD 0.03) to 0.08 (SD 0.05) and the mean titanium levels increased from 0.35 (SD 0.13) to 0.78 (SD 0.29). The femoral BMD ratio decreased in Gruen Zone 1 (91.9%) at five years postoperatively compared with the baseline scores at six weeks potoperatively. The femoral BMD ratio was maintained in Gruen zones 2 to 7. Conclusion. The use of a modular DM component and a cementless, tapered femoral stem shows excellent mid-term survivorship with minimal concerns for corrosion and metal ion release in a cohort of young, active patients undergoing primary THA. Cite this article: Bone Joint J 2021;103-B(7 Supple B):73–77


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 872 - 880
1 May 2021
Young PS Macarico DT Silverwood RK Farhan-Alanie OM Mohammed A Periasamy K Nicol A Meek RMD

Aims. Uncemented metal acetabular components show good osseointegration, but material stiffness causes stress shielding and retroacetabular bone loss. Cemented monoblock polyethylene components load more physiologically; however, the cement bone interface can suffer fibrous encapsulation and loosening. It was hypothesized that an uncemented titanium-sintered monoblock polyethylene component may offer the optimum combination of osseointegration and anatomical loading. Methods. A total of 38 patients were prospectively enrolled and received an uncemented monoblock polyethylene acetabular (pressfit) component. This single cohort was then retrospectively compared with previously reported randomized cohorts of cemented monoblock (cemented) and trabecular metal (trabecular) acetabular implants. The primary outcome measure was periprosthetic bone density using dual-energy x-ray absorptiometry over two years. Secondary outcomes included radiological and clinical analysis. Results. Although there were differences in the number of males and females in each group, no significant sex bias was noted (p = 0.080). Furthermore, there was no significant difference in age (p = 0.910) or baseline lumbar bone mineral density (BMD) (p = 0.998) found between any of the groups (pressfit, cemented, or trabecular). The pressfit implant initially behaved like the trabecular component with an immediate fall in BMD in the inferior and medial regions, with preserved BMD laterally, suggesting lateral rim loading. However, the pressfit component subsequently showed a reversal in BMD medially with recovery back towards baseline, and a continued rise in lateral BMD. This would suggest that the pressfit component begins to reload the medial bone over time, more akin to the cemented component. Analysis of postoperative radiographs revealed no pressfit component subsidence or movement up to two years postoperatively (100% interobserver reliability). Medial defects seen immediately postoperatively in five cases had completely resolved by two years in four patients. Conclusion. Initially, the uncemented monoblock component behaved similarly to the rigid trabecular metal component with lateral rim loading; however, over two years this changed to more closely resemble the loading pattern of a cemented polyethylene component with increasing medial pelvic loading. This indicates that the uncemented monoblock acetabular component may result in optimized fixation and preservation of retroacetabular bone stock. Cite this article: Bone Joint J 2021;103-B(5):872–880


Bone & Joint Research
Vol. 10, Issue 5 | Pages 298 - 306
1 May 2021
Dolkart O Kazum E Rosenthal Y Sher O Morag G Yakobson E Chechik O Maman E

Aims

Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model.

Methods

A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 644 - 649
1 Apr 2021
Alsousou J Oragu E Martin A Strickland L Newman S Kendrick B Taylor A Glyn-Jones S

Aims. The aim of this prospective cohort study was to evaluate the early migration of the TriFit cementless proximally coated tapered femoral stem using radiostereometric analysis (RSA). Methods. A total of 21 patients (eight men and 13 women) undergoing primary total hip arthroplasty (THA) for osteoarthritis of the hip were recruited in this study and followed up for two years. Two patients were lost to follow-up. All patients received a TriFit stem and Trinity Cup with a vitamin E-infused highly cross-linked ultra-high molecular weight polyethylene liner. Radiographs for RSA were taken postoperatively and then at three, 12, and 24 months. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and adverse events were reported. Results. At two years, the mean subsidence of the head and tip for the TriFit stem was 0.38 mm (SD 0.32) and 0.52 mm (SD 0.36), respectively. The total migration of the head and tip was 0.55 mm (SD 0.32) and 0.71 mm (SD 0.38), respectively. There were no statistically significant differences between the three to 12 months' migration (p = 0.105) and 12 to 24 months' migration (p = 0.694). The OHS and EQ-5D showed significant improvements at two years. Conclusion. The results of this study suggest that the TriFit femoral stem achieves initial stability and is likely to be stable in the mid and long term. A long-term outcome study is required to assess late mechanisms of failure and the effects of bone mineral density (BMD) related changes. Cite this article: Bone Joint J 2021;103-B(4):644–649


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 462 - 468
1 Mar 2021
Mendel T Schenk P Ullrich BW Hofmann GO Goehre F Schwan S Klauke F

Aims

Minimally invasive fixation of pelvic fragility fractures is recommended to reduce pain and allow early mobilization. The purpose of this study was to evaluate the outcome of two different stabilization techniques in bilateral fragility fractures of the sacrum (BFFS).

Methods

A non-randomized, prospective study was carried out in a level 1 trauma centre. BFFS in 61 patients (mean age 80 years (SD 10); four male, 57 female) were treated surgically with bisegmental transsacral stablization (BTS; n = 41) versus spinopelvic fixation (SP; n = 20). Postoperative full weightbearing was allowed. The outcome was evaluated at two timepoints: discharge from inpatient treatment (TP1; Fitbit tracking, Zebris stance analysis), and ≥ six months (TP2; Fitbit tracking, Zebris analysis, based on modified Oswestry Disability Index (ODI), Majeed Score (MS), and the 12-Item Short Form Survey 12 (SF-12). Fracture healing was assessed by CT. The primary outcome parameter of functional recovery was the per-day step count; the secondary parameter was the subjective outcome assessed by questionnaires.


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


Bone & Joint 360
Vol. 10, Issue 1 | Pages 24 - 28
1 Feb 2021


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 98 - 104
1 Jan 2021
van Ooij B Sierevelt IN van der Vis HM Hoornenborg D Haverkamp D

Aims

For many designs of total knee arthroplasty (TKA) it remains unclear whether cemented or uncemented fixation provides optimal long-term survival. The main limitation in most studies is a retrospective or non-comparative study design. The same is true for comparative trials looking only at the survival rate as extensive sample sizes are needed to detect true differences in fixation and durability. Studies using radiostereometric analysis (RSA) techniques have shown to be highly predictive in detecting late occurring aseptic loosening at an early stage. To investigate the difference in predicted long-term survival between cemented, uncemented, and hybrid fixation of TKA, we performed a randomized controlled trial using RSA.

Methods

A total of 105 patients were randomized into three groups (cemented, uncemented, and hybrid fixation of the ACS Mobile Bearing (ACS MB) knee system, implantcast). RSA examinations were performed on the first day after surgery and at scheduled follow-up visits at three months, six months, one year, and two years postoperatively. Patient-reported outcome measures (PROMs) were obtained preoperatively and after two years follow-up. Patients and follow-up investigators were blinded for the result of randomization.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 41 - 50
1 Jan 2021
Wong RMY Choy VMH Li J Li TK Chim YN Li MCM Cheng JCY Leung K Chow SK Cheung WH

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Methods

A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 10 - 21
1 Jan 2021
Zong Z Zhang X Yang Z Yuan W Huang J Lin W Chen T Yu J Chen J Cui L Li G Wei B Lin S

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

Methods

Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.


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


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1717 - 1722
1 Dec 2020
Kang T Park SY Lee JS Lee SH Park JH Suh SW

Aims

As the population ages and the surgical complexity of lumbar spinal surgery increases, the preoperative stratification of risk becomes increasingly important. Understanding the risks is an important factor in decision-making and optimizing the preoperative condition of the patient. Our aim was to determine whether the modified five-item frailty index (mFI-5) and nutritional parameters could be used to predict postoperative complications in patients undergoing simple or complex lumbar spinal fusion.

Methods

We retrospectively reviewed 584 patients who had undergone lumbar spinal fusion for degenerative lumbar spinal disease. The 'simple' group (SG) consisted of patients who had undergone one- or two-level posterior lumbar fusion. The 'complex' group (CG) consisted of patients who had undergone fusion over three or more levels, or combined anterior and posterior surgery. On admission, the mFI-5 was calculated and nutritional parameters collected.


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1475 - 1483
7 Nov 2020
Oliver WM Searle HKC Ng ZH Wickramasinghe NRL Molyneux SG White TO Clement ND Duckworth AD

Aims

The aim of this study was to determine the current incidence and epidemiology of humeral diaphyseal fractures. The secondary aim was to explore variation in patient and injury characteristics by fracture location within the humeral diaphysis.

Methods

Over ten years (2008 to 2017), all adult patients (aged ≥ 16 years) sustaining an acute fracture of the humeral diaphysis managed at the study centre were retrospectively identified from a trauma database. Patient age, sex, medical/social background, injury mechanism, fracture classification, and associated injuries were recorded and analyzed.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 731 - 741
28 Oct 2020
He Z Nie P Lu J Ling Y Guo J Zhang B Hu J Liao J Gu J Dai B Feng Z

Aims. Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion. Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741


Bone & Joint Research
Vol. 9, Issue 10 | Pages 675 - 688
1 Oct 2020
Shao L Gou Y Fang J Hu Y Lian Q Zhang Y Wang Y Tian F Zhang L

Aims. Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688


Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 534 - 542
1 Sep 2020
Varga P Inzana JA Fletcher JWA Hofmann-Fliri L Runer A Südkamp NP Windolf M

Aims

Fixation of osteoporotic proximal humerus fractures remains challenging even with state-of-the-art locking plates. Despite the demonstrated biomechanical benefit of screw tip augmentation with bone cement, the clinical findings have remained unclear, potentially as the optimal augmentation combinations are unknown. The aim of this study was to systematically evaluate the biomechanical benefits of the augmentation options in a humeral locking plate using finite element analysis (FEA).

Methods

A total of 64 cement augmentation configurations were analyzed using six screws of a locking plate to virtually fix unstable three-part fractures in 24 low-density proximal humerus models under three physiological loading cases (4,608 simulations). The biomechanical benefit of augmentation was evaluated through an established FEA methodology using the average peri-screw bone strain as a validated predictor of cyclic cut-out failure.


Bone & Joint 360
Vol. 9, Issue 4 | Pages 23 - 26
1 Aug 2020


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.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 368 - 385
1 Jul 2020
Chow SK Chim Y Wang J Wong RM Choy VM Cheung W

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 861 - 867
1 Jul 2020
Hiranaka T Yoshikawa R Yoshida K Michishita K Nishimura T Nitta S Takashiba K Murray D

Aims

Cementless unicompartmental knee arthroplasty (UKA) has advantages over cemented UKA, including improved fixation, but has a higher risk of tibial plateau fracture, particularly in Japanese patients. The aim of this multicentre study was to determine when cementless tibial components could safely be used in Japanese patients based on the size and shape of the tibia.

Methods

The study involved 212 cementless Oxford UKAs which were undertaken in 174 patients in six hospitals. The medial eminence line (MEL), which is a line parallel to the tibial axis passing through the tip of medial intercondylar eminence, was drawn on preoperative radiographs. Knees were classified as having a very overhanging medial tibial condyle if this line passed medial to the medial tibial cortex. They were also classified as very small if a size A/AA tibial component was used.


The Bone & Joint Journal
Vol. 102-B, Issue 6 | Pages 766 - 771
1 Jun 2020
Coughlin TA Nightingale JM Myint Y Forward DP Norrish AR Ollivere BJ

Aims

Hip fractures in patients < 60 years old currently account for only 3% to 4% of all hip fractures in England, but this proportion is increasing. Little is known about the longer-term patient-reported outcomes in this potentially more active population. The primary aim is to examine patient-reported outcomes following isolated hip fracture in patients aged < 60 years. The secondary aim is to determine an association between outcomes and different types of fracture pattern and/or treatment implants.

Methods

All hip fracture patients aged 18 to 60 years admitted to a single centre over a 15-year period were used to identify the study group. Fracture pattern (undisplaced intracapsular, displaced intracapsular, and extracapsular) and type of operation (multiple cannulated hip screws, angular stable fixation, hemiarthroplasty, and total hip replacement) were recorded. The primary outcome measures were the Oxford Hip Score (OHS), the EuroQol five-dimension questionnaire (EQ-5D-3L), and EQ-visual analogue scale (VAS) scores. Preinjury scores were recorded by patient recall and postinjury scores were collected at a mean of 57 months (9 to 118) postinjury. Ethics approval was obtained prior to study commencement.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 314 - 321
1 Jun 2020
Bliven E Sandriesser S Augat P von Rüden C Hackl S

Aims

Evaluate if treating an unstable femoral neck fracture with a locking plate and spring-loaded telescoping screw system would improve construct stability compared to gold standard treatment methods.

Methods

A 31B2 Pauwels’ type III osteotomy with additional posterior wedge was cut into 30 fresh-frozen femur cadavers implanted with either: three cannulated screws in an inverted triangle configuration (CS), a sliding hip screw and anti-rotation screw (SHS), or a locking plate system with spring-loaded telescoping screws (LP). Dynamic cyclic compressive testing representative of walking with increasing weight-bearing was applied until failure was observed. Loss of fracture reduction was recorded using a high-resolution optical motion tracking system.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 139 - 145
1 Mar 2020
Guebeli A Platz EA Paller CJ McGlynn KA Rohrmann S

Aims. To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results. Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion. In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Methods

We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 268 - 272
1 Feb 2020
Diarbakerli E Savvides P Wihlborg A Abbott A Bergström I Gerdhem P

Aims. Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls. Methods. We included 78 adolescents with idiopathic scoliosis (57 female patients) at a mean age of 13.7 years (8.5 to 19.6) and 52 age- and sex-matched healthy controls (39 female patients) at a mean age of 13.8 years (9.1 to 17.6). Mean skeletal age, estimated according to the Tanner-Whitehouse 3 system (TW3), was 13.4 years (7.4 to 17.8) for those with idiopathic scoliosis, and 13.1 years (7.4 to 16.5) for the controls. Mean Cobb angle for those with idiopathic scoliosis was 29° (SD 11°). All individuals were scanned with dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) of the left radius and tibia to assess bone density. Statistical analyses were performed with independent-samples t-test, the Mann-Whitney U test, and the chi-squared test. Results. Compared with controls, adolescents with idiopathic scoliosis had mean lower DXA values in the left femoral neck (0.94 g/cm. 2. (SD 0.14) vs 1.00 g/cm. 2. (SD 0.15)), left total hip (0.94 g/cm. 2. (SD 0.14) vs 1.01 g/cm. 2. (SD 0.17)), L1 to L4 (0.99 g/cm. 2. (SD 0.15) vs 1.06 g/cm. 2. (SD 0.17)) and distal radius (0.35 g/cm. 2. (SD 0.07) vs 0.39 g/cm. 2. (SD 0.08; all p ≤ 0.024), but not in the mid-radius (0.72 g/cm. 2. vs 0.74 g/cm. 2. ; p = 0.198, independent t-test) and total body less head (1,559 g (SD 380) vs 1,649 g (SD 492; p = 0.0.247, independent t-test). Compared with controls, adolescents with idiopathic scoliosis had lower trabecular volume bone mineral density (BMD) on pQCT in the distal radius (184.7 mg/cm. 3. (SD 40.0) vs 201.7 mg/cm. 3. (SD 46.8); p = 0.029), but not in other parts of the radius or the tibia (p ≥ 0.062, Mann-Whitney U test). Conclusion. In the present study, idiopathic scoliosis patients seemed to have lower BMD at central skeletal sites and less evident differences at peripheral skeletal sites when compared with controls. Cite this article: Bone Joint J 2020;102-B(2):268–272


Bone & Joint Research
Vol. 8, Issue 12 | Pages 573 - 581
1 Dec 2019
de Quadros VP Tobar N Viana LR dos Santos RW Kiyataka PHM Gomes-Marcondes MCC

Objectives

Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol.

Methods

Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy.


Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562


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.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1186 - 1191
1 Oct 2019
Amstutz HC Le Duff MJ

Aims

In previous studies, we identified multiple factors influencing the survivorship of hip resurfacing arthroplasties (HRAs), such as initial anatomical conditions and surgical technique. In addition, the University of California, Los Angeles (UCLA) activity score presents a ceiling effect, so a better quantification of activity is important to determine which activities may be advisable or detrimental to the recovered patient. We aimed to determine the effect of specific groups of sporting activities on the survivorship free of aseptic failure of a large series of HRA.

Patients and Methods

A total of 661 patients (806 hips) representing 77% of a consecutive series of patients treated with metal-on-metal hybrid HRA answered a survey to determine the types and amounts of sporting activities they regularly participated in. There were 462 male patients (70%) and 199 female patients (30%). Their mean age at the time of surgery was 51.9 years (14 to 78). Their mean body mass index (BMI) was 26.5 kg/m2 (16.7 to 46.5). Activities were regrouped into 17 categories based on general analogies between these activities. Scores for typical frequency and duration of the sessions were used to quantify the patients’ overall time spent engaging in sporting activities. Impact and cycle scores were computed. Multivariable models were used.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1307 - 1312
1 Oct 2019
Jacxsens M Schmid J Zdravkovic V Jost B Spross C

Aims

In order to determine whether and for whom serial radiological evaluation is necessary in one-part proximal humerus fractures, we set out to describe the clinical history and predictors of secondary displacement in patients sustaining these injuries.

Patients and Methods

Between January 2014 and April 2016, all patients with an isolated, nonoperatively treated one-part proximal humerus fracture were prospectively followed up. Clinical and radiological evaluation took place at less than two, six, 12, and 52 weeks. Fracture configuration, bone quality, and comminution were determined on the initial radiographs. Fracture healing, secondary displacement, and treatment changes were recorded during follow-up.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 472 - 480
1 Oct 2019
Hjorthaug GA Søreide E Nordsletten L Madsen JE Reinholt FP Niratisairak S Dimmen S

Objectives

Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

Methods

A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats. A ‘parecoxib immediate’ (Pi) group received parecoxib (3.2 mg/kg bodyweight twice per day) on days 0, 1, and 2. A ‘parecoxib delayed’ (Pd) group received the same dose of parecoxib on days 3, 4, and 5. A control group received saline only. Fracture healing was evaluated by biomechanical tests, histomorphometry, and dual-energy x-ray absorptiometry (DXA) at four weeks.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 489 - 494
1 Oct 2019
Klasan A Bäumlein M Dworschak P Bliemel C Neri T Schofer MD Heyse TJ

Objectives

Periprosthetic femoral fractures (PFFs) have a higher incidence with cementless stems. The highest incidence among various cementless stem types was observed with double-wedged stems. Short stems have been introduced as a bone-preserving alternative with a higher incidence of PFF in some studies. The purpose of this study was a direct load-to-failure comparison of a double-wedged cementless stem and a short cementless stem in a cadaveric fracture model.

Methods

Eight hips from four human cadaveric specimens (age mean 76 years (60 to 89)) and eight fourth-generation composite femurs were used. None of the cadaveric specimens had compromised quality (mean T value 0.4 (-1.0 to 5.7)). Each specimen from a pair randomly received either a double-wedged stem or a short stem. A materials testing machine was used for lateral load-to-failure test of up to a maximal load of 5000 N.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Materials and Methods

A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6).


Bone & Joint Research
Vol. 8, Issue 7 | Pages 349 - 356
1 Jul 2019
Starlinger J Kaiser G Thomas A Sarahrudi K

Objectives

The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels.

Methods

Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded.


Objectives

Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.

Methods

MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 255 - 265
1 Jun 2019
Hernigou J Schuind F

Objectives

The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular.

Methods

English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 275 - 287
1 Jun 2019
Clement ND Bardgett M Merrie K Furtado S Bowman R Langton DJ Deehan DJ Holland J

Objectives. Our primary aim was to describe migration of the Exeter stem with a 32 mm head on highly crosslinked polyethylene and whether this is influenced by age. Our secondary aims were to assess functional outcome, satisfaction, activity, and bone mineral density (BMD) according to age. Patients and Methods. A prospective cohort study was conducted. Patients were recruited into three age groups: less than 65 years (n = 65), 65 to 74 years (n = 68), and 75 years and older (n = 67). There were 200 patients enrolled in the study, of whom 115 were female and 85 were male, with a mean age of 69.9 years (sd 9.5, 42 to 92). They were assessed preoperatively, and at three, 12 and, 24 months postoperatively. Stem migration was assessed using Einzel-Bild-Röntgen-Analyse (EBRA). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), EuroQol-5 domains questionnaire (EQ-5D), short form-36 questionnaire (SF-36,) and patient satisfaction were used to assess outcome. The Lower Extremity Activity Scale (LEAS), Timed Up and Go (TUG) test, and activPAL monitor (energy expelled, time lying/standing/walking and step count) were used to assess activity. The BMD was assessed in Gruen and Charnley zones. Results. Mean varus/valgus tilt was -0.77⁰ and axial subsidence was -1.20 mm. No significant difference was observed between age groups (p ⩾ 0.07). There was no difference according to age group for postoperative WOMAC (p ⩾ 0.11), HHS (p ⩾ 0.06), HOOS (p ⩾ 0.46), EQ-5D (p ⩾ 0.38), patient satisfaction (p ⩾ 0.05), or activPAL (p ⩾ 0.06). Patients 75 years and older had a worse SF-36 physical function (p = 0.01) and physical role (p = 0.03), LEAS score (p < 0.001), a shorter TUG (p = 0.01), and a lower BMD in Charnley zone 1 (p = 0.02). Conclusion. Exeter stem migration is within normal limits and is not influenced by age group. Functional outcome, patient satisfaction, activity level, and periprosthetic BMD are similar across all age groups. Cite this article: N. D. Clement, M. Bardgett, K. Merrie, S. Furtado, R. Bowman, D. J. Langton, D. J. Deehan, J. Holland. Cemented Exeter total hip arthroplasty with a 32 mm head on highly crosslinked polyethylene: Does age influence functional outcome, satisfaction, activity, stem migration, and periprosthetic bone mineral density? Bone Joint Res 2019;8:275–287. DOI: 10.1302/2046-3758.86.BJR-2018-0300.R1


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 365 - 371
1 Apr 2019
Nam D Salih R Nahhas CR Barrack RL Nunley RM

Aims. Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell (vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed ‘high-risk’ for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study’s purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design. Patients and Methods. This was a prospective study of patients between 18 and 65 years of age, with a body mass index (BMI) < 35 kg/m. 2. and University of California at Los Angeles (UCLA) activity score > 6, who received a modular cobalt-chromium acetabular liner, highly crosslinked polyethylene mobile bearing, and cementless titanium femoral stem for their primary THA. Patients with a history of renal disease and metal hardware elsewhere in the body were excluded. A total of 43 patients (30 male, 13 female; mean age 52.6 years (. sd. 6.5)) were enrolled. All patients had a minimum of two years’ clinical follow-up. Patient-reported outcome measures, whole blood metal ion levels (ug/l), and periprosthetic femoral BMD were measured at baseline, as well as at one and two years postoperatively. Power analysis indicated 40 patients necessary to demonstrate a five-fold increase in cobalt levels from baseline (alpha = 0.05, beta = 0.80). A mixed model with repeated measures was used for statistical analysis. Results. Mean Harris Hip Scores improved from 54.1 (. sd. 20.5) to 91.2 (. sd. 10.8) at two years postoperatively (p < 0.001). All patients had radiologically well-fixed components, no patients experienced any instability, and no patients required any further intervention. Mean cobalt levels increased from 0.065 ug/l (. sd. 0.03) preoperatively to 0.30 ug/l (. sd. 0.51) at one year postoperatively (p = 0.01) but decreased at two years postoperatively to 0.16 ug/l (. sd. 0.23; p = 0.2). Four patients (9.3%) had a cobalt level outside the reference range (0.03 ug/l to 0.29 ug/l) at two years postoperatively, with values from 0.32 ug/l to 0.94 ug/l. The mean femoral BMD ratio was maintained in Gruen zones 2 to 7 at both one and two years postoperatively using this stem design. At two years postoperatively, mean BMD in the medial calcar was 101.5% of the baseline value. Conclusion. Use of a modular DM prosthesis and cementless, tapered femoral stem has shown encouraging results in young, active patients undergoing primary THA. Elevation in mean cobalt levels and the presence of four patients outside the reference range at two years postoperatively demonstrates the necessity of continued surveillance in this cohort. Cite this article: Bone Joint J 2019;101-B:365–371


The Bone & Joint Journal
Vol. 101-B, Issue 1_Supple_A | Pages 32 - 40
1 Jan 2019
Hellman MD Ford MC Barrack RL

Aims

Surface replacement arthroplasty (SRA), compared with traditional total hip arthroplasty (THA), is more expensive and carries unique concern related to metal ions production and hypersensitivity. Additionally, SRA is a more demanding procedure with a decreased margin for error compared with THA. To justify its use, SRA must demonstrate comparable component survival and some clinical advantages. We therefore performed a systematic literature review to investigate the differences in complication rates, patient-reported outcomes, stress shielding, and hip biomechanics between SRA and THA.

Materials and Methods

A systematic review of the literature was completed using MEDLINE and EMBASE search engines. Inclusion criteria were level I to level III articles that reported clinical outcomes following primary SRA compared with THA. An initial search yielded 2503 potential articles for inclusion. Exclusion criteria included review articles, level IV or level V evidence, less than one year’s follow-up, and previously reported data. In total, 27 articles with 4182 patients were available to analyze.


The Bone & Joint Journal
Vol. 100-B, Issue 11 | Pages 1455 - 1462
1 Nov 2018
Munro JT Millar JS Fernandez JW Walker CG Howie DW Shim VB

Aims

Osteolysis, secondary to local and systemic physiological effects, is a major challenge in total hip arthroplasty (THA). While osteolytic defects are commonly observed in long-term follow-up, how such lesions alter the distribution of stress is unclear. The aim of this study was to quantitatively describe the biomechanical implication of such lesions by performing subject-specific finite-element (FE) analysis on patients with osteolysis after THA.

Patients and Methods

A total of 22 hemipelvis FE models were constructed in order to assess the transfer of load in 11 patients with osteolysis around the acetabular component of a THA during slow walking and a fall onto the side. There were nine men and two women. Their mean age was 69 years (55 to 81) at final follow-up. Changes in peak stress values and loads to fracture in the presence of the osteolytic defects were measured.


Bone & Joint Research
Vol. 7, Issue 11 | Pages 601 - 608
1 Nov 2018
Hsu W Hsu W Hung J Shen W Hsu RW

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


The Bone & Joint Journal
Vol. 100-B, Issue 9 | Pages 1175 - 1181
1 Sep 2018
Benca E Willegger M Wenzel F Hirtler L Zandieh S Windhager R Schuh R

Aims. The traditional transosseus flexor hallucis longus (FHL) tendon transfer for patients with Achilles tendinopathy requires two incisions to harvest a long tendon graft. The use of a bio-tenodesis screw enables a short graft to be used and is less invasive, but lacks supporting evidence about its biomechanical behaviour. We aimed, in this study, to compare the strength of the traditional transosseus tendon-to-tendon fixation with tendon-to-bone fixation using a tenodesis screw, in cyclical loading and ultimate load testing. Materials and Methods. Tendon grafts were undertaken in 24 paired lower-leg specimens and randomly assigned in two groups using fixation with a transosseus suture (suture group) or a tenodesis screw (screw group). The biomechanical behaviour was evaluated using cyclical and ultimate loading tests. The Student’s t-test was performed to assess statistically significant differences in bone mineral density (BMD), displacement, the slope of the load-displacement curves, and load to failure. Results. The screw group showed less displacement (loosening) during cyclical loading, which was significant during 300, 500, 600, 700, 800, 900, and 1000 cycles (p < 0.05: other cycles: 0.079 < p < 0.402). Compared with the suture group, the screw group had higher mean ultimate load values (133.6 N, . sd. 73.5 vs 110.1 N,. sd. 46.2; p = 0.416). Conclusion. Fixation of the FHL tendon with a tenodesis screw enables a less invasive procedure to be undertaken and shows similar biomechanical behaviour and primary strength compared with fixation using a transosseus suture. Cite this article: Bone Joint J 2018;100-B:1175–81


The Bone & Joint Journal
Vol. 100-B, Issue 9 | Pages 1148 - 1156
1 Sep 2018
Ferguson RJ Broomfield JA Malak TT Palmer AJR Whitwell D Kendrick B Taylor A Glyn-Jones S

Aims

The aim of this study was to determine the stability of a new short femoral stem compared with a conventional femoral stem in patients undergoing cementless total hip arthroplasty (THA), in a prospective randomized controlled trial using radiostereometric analysis (RSA).

Patients and Methods

A total of 53 patients were randomized to receive cementless THA with either a short femoral stem (MiniHip, 26 patients, mean age: 52 years, nine male) or a conventional length femoral stem (MetaFix, 23 patients, mean age: 53 years, 11 male). All patients received the same cementless acetabular component. Two-year follow-up was available on 38 patients. Stability was assessed through migration and dynamically inducible micromotion. Radiographs for RSA were taken postoperatively and at three, six, 12, 18, and 24 months.


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


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.