Journal of Bone and Mineral Metabolism最新文献

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: Despite the increasing number of anti-osteoporotic medications for improving bone mineral density (BMD) and reducing fracture risk, some patients show unsatisfactory responses.

Materials and methods: We retrospectively analyzed 2134 patients who received anti-osteoporotic medications between March 2020 and October 2024. BMD percentage changes at the lumbar spine, femoral neck, and total hip were assessed after 1 year. Patients were categorized as "non-BMD gainers" (<3% increase at all sites) or "BMD gainers" (≥3% increase at any site). Multivariable logistic regression was used to evaluate associations with non-BMD gainer status, including age, body mass index, baseline T-score, and medication class.

Results: 578 patients (27.1%) were classified as non-BMD gainers. The observed rates of non-BMD gainer varied across medication classes in this real-world cohort, with selective estrogen receptor modulators (SERMs) showing the highest non-BMD gain rate (46.0%), followed by bisphosphonates (32.2%), teriparatide (35.1%), denosumab (19.5%), and romosozumab (5.6%). Non-BMD gainers had high baseline BMD and low bone turnover markers, and were more likely to have a history of osteoporosis treatment. In multivariable logistic regression analysis, older age (≥75 years), SERM use, and high baseline BMD T-scores were independently associated with increased risk of non-BMD gainer status. Conversely, low T-scores (≤-3.0) were associated with a significantly reduced likelihood of being a non-BMD gainer.

Conclusion: Approximately 25% of patients did not achieve BMD gain after 1 year of treatment. Older age, higher baseline BMD T-scores, and SERM use were associated with an increased probability of non-BMD gainer status in this observational study.

Introduction: Although bone anabolic agents such as teriparatide are effective for osteoporosis, satisfaction and adherence may vary by regimen. This multicenter study assessed long-term satisfaction, persistence, efficacy, and safety in postmenopausal women with primary osteoporosis treated with alternating daily and twice-weekly teriparatide over 52 weeks, followed by a final free-choice treatment period.

Materials and methods: In a randomized, open-label, crossover study, 358 postmenopausal women at high risk for fracture were assigned to receive once-daily (20 µg) or twice-weekly (28.2 µg) subcutaneous teriparatide for 26 weeks, then crossed over to the alternative regimen for another 26 weeks. Afterwards, 233 patients entered a 52-week free-choice period under their preferred regimen.

Results: Among the 233 patients entering the free-choice period, 162 chose twice-weekly and 71 chose daily teriparatide. Persistence at 104 weeks was 90.1% for twice-weekly and 88.7% for daily groups (p = 0.749). Overall and treatment satisfaction between groups did not differ significantly at 104 weeks (p > 0.05). Fracture incidence was low and similar (2.8% vs. 1.2%, p = 0.758). Patients in both groups showed significant increases in bone mineral density at L2-L4 and the femoral neck (p < 0.05). Adverse events were infrequent and non-severe.

Conclusions: Patient satisfaction and efficacy were maintained with both teriparatide regimens over 104 weeks, and persistence improved during the patient-choice phase. Supporting patient preference may improve adherence to osteoporosis medications.

Clinical trial registration: Japan Registry of Clinical Trials ID: jRCTs031210187.