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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Aims. The aim of this study was to investigate the impact of the level of upper instrumented vertebra (UIV) in frail patients undergoing surgery for adult spine deformity (ASD). Methods. Patients with adult spinal deformity who had undergone T9-to-pelvis fusion were stratified using the ASD-Modified Frailty Index into not frail, frail, and severely frail categories. ASD was defined as at least one of: scoliosis ≥ 20°, sagittal vertical axis (SVA) ≥ 5 cm, or pelvic tilt ≥ 25°. Means comparisons tests were used to assess differences between both groups. Logistic regression analyses were used to analyze associations between frailty categories, UIV, and outcomes. Results. A total of 477 patients were included (mean age 60.3 years (SD 14.9), mean BMI 27.5 kg/m. 2. (SD 5.8), mean Charlson Comorbidity Index (CCI) 1.67 (SD 1.66)). Overall, 74% of patients were female (n = 353), and 49.6% of patients were not frail (237), 35.4% frail (n = 169), and 15% severely frail (n = 71). At baseline, differences in age, BMI, CCI, and deformity were significant (all p = 0.001). Overall, 15.5% of patients (n = 74) had experienced mechanical complications by two years (8.1% not frail (n = 36), 15.1% frail (n = 26), and 16.3% severely frail (n = 12); p = 0.013). Reoperations also differed between groups (20.2% (n = 48) vs 23.3% (n = 39) vs 32.6% (n = 23); p = 0.011). Controlling for osteoporosis, baseline deformity, and degree of correction (by sagittal age-adjusted score (SAAS) matching), frail and severely frail patients were more likely to experience mechanical complications if they had heart failure (odds ratio (OR) 6.6 (95% CI 1.6 to 26.7); p = 0.008), depression (OR 5.1 (95% CI 1.1 to 25.7); p = 0.048), or cancer (OR 1.5 (95% CI 1.1 to 1.4); p = 0.004). Frail and severely frail patients experienced higher rates of mechanical complication than ‘not frail’ patients at two years (19% (n = 45) vs 11.9% (n = 29); p = 0.003). When controlling for baseline deformity and degree of correction in severely frail and frail patients, severely frail patients were less likely to experience clinically relevant proximal junctional kyphosis or failure or mechanical complications by two years, if they had a more proximal UIV. Conclusion. Frail patients are at risk of a poor outcome after surgery for adult spinal deformity due to their comorbidities. Although a definitively prescriptive upper instrumented vertebra remains elusive, these patients appear to be at greater risk for a poor outcome if the upper instrumented vertebra is sited more distally. Cite this article: Bone Joint J 2024;106-B(11):1342–1347