Aims

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

Aims

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

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

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740

Aims. The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis. Methods. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. Results. LINC01089 expression was reinforced in serum samples of OP patients, but it gradually diminished while hMSCs underwent osteogenic differentiation. LINC01089 knockdown facilitated hMSC osteogenic differentiation. This was substantiated by: the increase in ALP activity; ALP, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) messenger RNA (mRNA) levels; and level of ARS staining. Meanwhile, LINC01089 upregulation resulted in the opposite effects. LINC01089 targeted miR-1287-5p, and the LINC01089 knockdown-induced hMSC osteogenic differentiation was repressed by miR-1287-5p depletion. HSPA4 is a downstream function molecule of the LINC01089/miR-1287-5p pathway; miR-1287-5p negatively modulated HSPA4 levels and attenuated its functional effects. Conclusion. LINC01089 negatively regulated hMSC osteogenic differentiation, at least in part, via governing miR-1287-5p/HSPA4 signalling. These findings provide new insights into hMSC osteogenesis and bone metabolism. Cite this article: Bone Joint Res 2024;13(12):779–789

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