Journal of Bone and Mineral Metabolism最新文献

Introduction: Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, and bisphosphonates (BPs) are widely used for treatment. Localized cortical thickening (LCT, "beaking" or "flaring") is a characteristic radiographic finding and a potential precursor of atypical femoral fracture, a known complication of long-term BP use. The incidence of LCT and its association with BP duration in GIOP remain unclear.

Materials and methods: In this cross-sectional study, 86 outpatients with GIOP (mean age, 60.6 years; 62.8% women) were included. Femoral radiographs were evaluated for LCT, cortical thickness index (CTI; diaphyseal/subtrochanteric), and lateral bowing angle (LBA). Patients were stratified by BP duration (≥2 or ≥4 years), and 1:1 propensity score matching was used to evaluate the association with LCT. Associations of BP duration with CTI and LBA were analyzed using linear mixed-effects models; correlations with bone turnover markers (BTMs) and bone mineral density (BMD) were also examined.

Results: LCT was observed in 11 (12.8%) patients, including 10 undergoing BP therapy. Patients with LCT had a significantly longer duration of BP use (median: 8.0 years vs. 1.2 years, p <0.01). After matching, BP use for ≥4 years was significantly associated with LCT (odds ratio=11.29, p=0.01), whereas that for ≥2 years was not. Diaphyseal CTI significantly increased with BP duration; no associations were found with subtrochanteric CTI, LBA, BTMs, or BMD.

Conclusion: In GIOP, prolonged BP use, especially for ≥4 years, was associated with LCT and greater diaphyseal cortical thickness. Radiographic assessment is essential in patients with GIOP and long-term BP use.

Introduction: Accurate prediction of fracture risk is important for treatment decisions, yet evaluations of commonly used thresholds are limited, and the added value of volumetric bone mineral density (vBMD) remains uncertain. We conducted the first head-to-head comparison of the SHAFRE and FRAX algorithms using identical predictor information.

Materials and methods: We included 3525 community-dwelling Swedish men and women (mean age 71.4 years) who underwent a health examination with femoral neck areal BMD (aBMD) and radial vBMD. Incident fractures were retrieved from the National Patient Register. Model performance was evaluated using threshold-specific sensitivity and specificity.

Results: Over a mean follow-up of 8.7 years, 559 participants sustained a fracture. SHAFRE predicted a mean 10-year fracture risk of 21.9% in those who fractured versus 15.6% in the remaining cohort (ROC-area: 68%, 95% CI: 66-71%). Corresponding FRAX values were 16.7% and 12.6% (ROC-area: 66%, 95% CI: 63-68%), and FRAX slightly underestimated fracture risk in this cohort. Adding radial vBMD on top of aBMD did not materially improve discrimination for SHAFRE (70%, 95% CI: 67-72%) or FRAX (68%, 95% CI: 65-70%). Threshold-specific analysis identified an optimal predicted risk threshold of 13-17%, consistently below the commonly recommended 20%.

Conclusions: Predictive ability for major fractures remained modest for both algorithms and was not improved by adding vBMD. The estimated optimal threshold for treatment initiation was lower than the commonly recommended 20%. These findings reinforce that discrimination is substantially stronger for hip fracture than for major osteoporotic fractures.

Introduction: To determine the incidence and risk factors of fragility fractures and atypical femoral fracture (AFF)-related events in patients with systemic lupus erythematosus (SLE) receiving long-term glucocorticoid (GC) therapy.

Materials and methods: A retrospective analysis was conducted of 170 SLE patients followed from 2016 to 2023. Data on GC use, bisphosphonate (BP) therapy, bone-related events, and clinical characteristics were collected. Risk factors for fragility fractures and AFF-related events, including localized periosteal thickening (LPT), were analyzed using multivariate logistic regression.

Results: Although the median daily dose of prednisolone decreased over time, 82.9% of patients still met the criteria for pharmacologic intervention for GC-induced osteoporosis in 2023, and most continued to receive > 5 mg/day of GC. The median duration of BP therapy was 10.4 years, with 69 patients maintaining BP treatment throughout the observation period (median, 12.5 years). Fragility fractures and AFF-related events occurred in 7.6% and 5.8% of patients, respectively. Fragility fractures were independently associated with SLE flares and infection-related hospitalizations, whereas AFF-related events were significantly associated with prolonged BP use.

Conclusion: Despite a gradual reduction in GC dosage, many patients with longstanding SLE remain at elevated risk for fractures. The comparable frequencies of fragility fractures and AFF-related events highlight the clinical relevance of both complications. The prevention of SLE flares and infections may contribute to lowering the risk of fragility fractures. In addition, careful monitoring for AFF/LPT is warranted in patients receiving long-term BP and GC therapy.

Arthritis represents a group of chronic joint diseases characterised by persistent inflammation, pain, and progressive tissue damage. Despite advances in therapeutic management, many patients experience incomplete symptom relief, highlighting the need to better understand the underlying mechanisms that sustain inflammation and pain. Emerging evidence indicates that neuroimmune interactions within the joint microenvironment play a central role in the pathogenesis of arthritis. The synovium, a thin membrane that lines the joint cavity, is the primary site of pathology in arthritis and serves as a dynamic interface integrating immune, vascular, and neural components. Under physiological conditions, tissue-resident macrophages, fibroblasts, and sensory nerve fibres maintain joint homeostasis. However, during arthritis, the synovium undergoes extensive remodelling, including hyperplasia, angiogenesis, and nerve fibre sprouting, which together amplify inflammatory and nociceptive signalling. Distinct macrophage subsets within the synovium exhibit specialised roles in mediating inflammation and communicating with neurons. Macrophage-derived cytokines such as IL-1β, IL-6, and TNF-α can directly sensitise nociceptors, whilst chemokines like CCL2 engage neuronal receptors to enhance excitability. Conversely, activated sensory neurons release neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP), which can modulate immune cell behaviour. Sympathetic signalling further contributes to immune modulation and correlates with disease severity. Together, these studies reveal that arthritis progression and chronic pain are shaped by reciprocal signalling between the nervous and immune systems. Understanding these complex pathways offers new perspectives for therapeutic intervention, suggesting that targeting neuroimmune crosstalk could provide dual benefits-reducing inflammation whilst alleviating chronic pain in arthritic disease.

Introduction: Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone and dorsal root ganglia (DRGs). It also quantifies nerve markers in serum of patients with or without osteoporotic fractures and pain.

Material and methods: Ovariectomy (OVX) or Sham surgery (Sham-OVX) of C57/Bl6 mice was performed (n = 10/group) and evoked and spontaneous pain behaviours assessed. In another experiment, OVX or Sham-OVX mice underwent a femoral osteotomy or sham osteotomy (n = 8/group) and pain behaviours measured. Gene expression of pain markers in bone and DRGs was quantified by RT-PCR. Nerve markers were quantified in serum of osteoporotic patients with or without fractures and pain using specific ELISAs.

Results: OVX did not cause changes in pain behaviours nor alter nociceptive gene expression in bone and DRGs. Osteotomy and Sham osteotomy both affected pain behaviours in mice compared to non-operated controls but did not significantly change nociceptive gene expression in bone and DRGs. OVX before osteotomy worsens weight-bearing compared to Sham-OVX. Fracture and pain did not affect nerve markers expression levels in serum of osteoporotic patients.

Conclusion: This study demonstrates that OVX and subsequent bone loss in mice are insufficient to induce pain behaviours but may intensify pain after fracture. Our clinical analysis does not show a correlation between circulating nerve markers and fracture pain reported by the patients but suggests possible sex differences in pain markers that need to be further investigated.

Introduction: Osteoclasts and foreign body giant cells (FBGCs) are multi-nuclear cells established by fusion of their mono-nuclear forms. Multi-nucleation via cell-cell fusion is a common characteristic of osteoclasts and FBGCs, and Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) and Osteoclast Stimulatory Transmembrane Protein (OC-STAMP) are both required for the process. Thus, it is thought that DC-STAMP and OC-STAMP interaction likely induces this fusion, but details of these mechanisms are not clear.

Materials and methods: We crossed DC-STAMP knockout (KO) with OC-STAMP KO mice to obtain DC-STAMP/OC-STAMP doubly deficient (DKO) mice. Osteoclasts and FBGC common progenitors were isolated from wild-type (WT), DC-STAMP KO, OC-STAMP KO or DKO mice. We then set up 4 co-culture systems: (1) WT with DC-STAMP KO cells, (2) WT with OC-STAMP KO cells, (3) WT with DKO cells, and (4) DC-STAMP KO with OC-STAMP KO cells to induce osteoclast or FBGC formation. We evaluated osteoclast and FBGC formation by TRAP and May-Gruenwald Giemsa staining, respectively. Finally, we performed bone morphometric analysis of WT, DC-STAMP KO, OC-STAMP KO, and DKO mice.

Results: Cell-cell fusion occurs normally in co-cultures of DC KO with WT cells, OC KO with WT cells, and DKO with WT cells in both osteoclast and FBGC-inducing conditions. By contrast, co-cultures of DC-STAMP KO with OC-STAMP KO cells did not show cell-cell fusion. Bone morphometric analysis revealed enhanced bone formation in DKO mice.

Conclusion: DC-STAMP and OC-STAMP cooperate to promote osteoclast and FBGC cell-cell fusion. DC-STAMP and OC-STAMP doubly deficient mice exhibit increased osteogenesis.