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Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1017 - 1024
1 Sep 2022
Morris WZ Justo PGS Williams KA Kim Y Millis MB Novais EN

Aims

The aims of this study were to characterize the incidence and risk factors associated with stress fractures following periacetabular osteotomy, and to determine their effect on osteotomy union.

Methods

We retrospectively reviewed all periacetabular osteotomies (PAOs) performed for developmental dysplasia of the hip (DDH) at one institution over a six-year period between 2012 and 2017. Perioperative factors were recorded, and included demographic and surgical data. Postoperatively, patients were followed for a minimum of one year with anteroposterior and false profile radiographs of the pelvis to monitor for evidence of stress fracture and union of osteotomies. We characterized the incidence and locations of stress fractures, and used univariate and multivariable analysis to identify factors predictive of stress fracture and the association of stress fracture on osteotomy union.


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 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 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.


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.


The Bone & Joint Journal
Vol. 104-B, Issue 4 | Pages 510 - 518
1 Apr 2022
Perry DC Arch B Appelbe D Francis P Craven J Monsell FP Williamson P Knight M

Aims

The aim of this study was to evaluate the epidemiology and treatment of Perthes’ disease of the hip.

Methods

This was an anonymized comprehensive cohort study of Perthes’ disease, with a nested consented cohort. A total of 143 of 144 hospitals treating children’s hip disease in the UK participated over an 18-month period. Cases were cross-checked using a secondary independent reporting network of trainee surgeons to minimize those missing. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants.


Bone & Joint 360
Vol. 11, Issue 1 | Pages 47 - 49
1 Feb 2022


Bone & Joint Open
Vol. 3, Issue 2 | Pages 158 - 164
17 Feb 2022
Buddhdev P Vallim F Slattery D Balakumar J

Aims

Slipped upper femoral epiphysis (SUFE) has well documented biochemical and mechanical risk factors. Femoral and acetabular morphologies seem to be equally important. Acetabular retroversion has a low prevalence in asymptomatic adults. Hips with dysplasia, osteoarthritis, and Perthes’ disease, however, have higher rates, ranging from 18% to 48%. The aim of our study was to assess the prevalence of acetabular retroversion in patients presenting with SUFE using both validated radiological signs and tomographical measurements.

Methods

A retrospective review of all SUFE surgical cases presenting to the Royal Children’s Hospital, Melbourne, Australia, from 2012 to 2019 were evaluated. Preoperative plain radiographs were assessed for slip angle, validated radiological signs of retroversion, and standardized postoperative CT scans were used to assess cranial and mid-acetabular version.


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

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

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


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 321 - 330
1 Mar 2022
Brzeszczynski F Brzeszczynska J Duckworth AD Murray IR Simpson AHRW Hamilton DF

Aims

Sarcopenia is characterized by a generalized progressive loss of skeletal muscle mass, strength, and physical performance. This systematic review primarily evaluated the effects of sarcopenia on postoperative functional recovery and mortality in patients undergoing orthopaedic surgery, and secondarily assessed the methods used to diagnose and define sarcopenia in the orthopaedic literature.

Methods

A systematic search was conducted in MEDLINE, EMBASE, and Google Scholar databases according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies involving sarcopenic patients who underwent defined orthopaedic surgery and recorded postoperative outcomes were included. The quality of the criteria by which a diagnosis of sarcopenia was made was evaluated. The quality of the publication was assessed using Newcastle-Ottawa Scale.


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1017 - 1026
1 Dec 2021
Sadiq S Lipski C Hanif U Arshad F Chaudary M Chaudhry F

Aims

This study assessed the impact of COVID-19 on hip and distal femur fracture patient outcomes across three successive UK lockdown periods over one year.

Methods

A single-centre retrospective cohort study was performed at an acute NHS Trust. Hip and distal femur fracture patients admitted within the first month from each of the three starting dates of each national lockdown were included and compared to a control group in March 2019. Data were collected as per the best practice tariff outcomes including additional outcomes as required. Data collection included COVID-19 status, time to theatre, 30-day mortality, presence of acute kidney injury (AKI) and pneumonia, and do not attempt cardiopulmonary resuscitation (DNACPR) status. Data were analyzed using an independent-samples t-test or chi-squared test with Fisher’s exact test where applicable. A p-value of < 0.05 was considered statistically significant.


Bone & Joint 360
Vol. 8, Issue 5 | Pages 21 - 24
1 Oct 2019


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.


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 9 | Pages 611 - 618
27 Sep 2021
Ali E Birch M Hopper N Rushton N McCaskie AW Brooks RA

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Methods

Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization.


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 184 - 191
1 Jan 2021
Perrin DL Visgauss JD Wilson DA Griffin AM Abdul Razak AR Ferguson PC Wunder JS

Aims

Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

Methods

Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma.


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 10 | Pages 1578 - 1585
1 Oct 2021
Abram SGF Sabah SA Alvand A Price AJ

Aims

To compare rates of serious adverse events in patients undergoing revision knee arthroplasty with consideration of the indication for revision (urgent versus elective indications), and compare these with primary arthroplasty and re-revision arthroplasty.

Methods

Patients undergoing primary knee arthroplasty were identified in the national Hospital Episode Statistics (HES) between 1 April 1997 to 31 March 2017. Subsequent revision and re-revision arthroplasty procedures in the same patients and same knee were identified. The primary outcome was 90-day mortality and a logistic regression model was used to investigate factors associated with 90-day mortality and secondary adverse outcomes, including infection (undergoing surgery), pulmonary embolism, myocardial infarction, and stroke. Urgent indications for revision arthroplasty were defined as infection or fracture, and all other indications (e.g. loosening, instability, wear) were included in the elective indications cohort.


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.