Calcified Tissue International最新文献

Follicle-stimulating hormone (FSH) was independently associated with lumbar spine (LS) bone mineral density (BMD), while estradiol (E2) predicted femoral neck BMD. A threshold effect for FSH (~ 15 mIU/mL) suggests site-specific and non-linear hormonal influences on bone during the menopausal transition. To investigate the association between serum FSH levels and BMD in midlife women, and to determine whether these associations persist after adjustment for E2 and age, with particular attention to site-specific effects. We conducted a cross-sectional study of 224 women aged 45-60 years, selected from an institutional database. Inclusion required simultaneous measurements of serum FSH, E2, and BMD at the LS, femoral neck (FN), and total hip (TH) by dual-energy X-ray absorptiometry. Women using anti-osteoporotic drugs, hormone therapy, or medications affecting bone, were excluded. Analyses included non-parametric tests, Spearman's correlations, multivariable linear regression with log-transformed hormones and stepwise BIC selection, and segmented regression. FSH rose progressively across menopausal stages, while E2 declined,, paralleling lower BMD values. Higher FSH correlated inversely with LS (ρ = -0.26, p < 0.001) and FN-BMD (ρ = -0.29, p = 0.041), while E2 correlated positively with LS-BMD (ρ = 0.22, p = 0.018). In multivariable models, log-FSH remained independently associated with LS-BMD (β = -0.072, p = 0.009), whereas log-E2 was the only predictor at FN-BMD (β = 0.138, p = 0.020). No predictors were retained for TH-BMD. Segmented regression identified a breakpoint at ~ 15 mIU/mL of FSH, below which LS-BMD declined steeply (β = -0.007 g/cm² per mIU/mL), with a plateau thereafter. FSH and E2 exert distinct, site-specific influences on bone. FSH was independently associated with LS-BMD and showed a threshold effect, while E2 was more relevant to FN. These findings suggest that menopausal bone loss is not solely estrogen-driven but also involves gonadotropin-mediated mechanisms.

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and occurs in both high- and low-turnover bone disorders. While phosphate (P) control is known to reduce adverse effects, most supporting studies have focused on high-turnover models. This study evaluates the effects of two P binders-calcium carbonate (CaCO₃) and sevelamer carbonate-on laboratorial markers and bone histomorphometry in a low-turnover bone disease model. Wistar rats underwent 5/6 nephrectomy and total parathyroidectomy (Nx + PTx) to induce low-turnover bone disease. Animals were assigned to 4 groups: Sham, untreated Nx + PTx, Nx + PTx + CaCO₃, and Nx + PTx + sevelamer. After 8 weeks, we performed biochemical analysis, bone histomorphometry, gene expression (SOST, β-catenin, DKK-1), immunohistochemistry (sclerostin, β-catenin, FGF23, DKK-1), and apoptosis assays. Bone histology confirmed low-turnover disease in Nx + PTx rats, which also developed CKD and hyperphosphatemia. Both P binders effectively reduced serum P levels, but only CaCO₃ corrected hypocalcemia. Notably, CaCO₃ treatment led to increased osteoid parameters, elevated osteoblast surface and absence of tetracycline labeling - hallmarks of osteomalacia. Moreover, CaCO₃ increased osteoblast apoptosis. In a rat model of low-turnover bone disease with normal dietary P, high-dose CaCO₃ impaired bone mineralization and induced osteomalacia. These findings highlight potential risks of calcium-based phosphate binders in patients with low bone turnover and hyperphosphatemia, supporting the need for careful clinical consideration and monitoring.

Opportunistic chest CT (OC-CT) presents significant potential for early osteoporosis screening. However, its application remains limited to specific patient populations, and the optimal vertebral level for osteoporosis detection has yet to be determined. This study aimed to determine the optimal vertebral level and assess the feasibility of OC-CT, with dual-energy X-ray absorptiometry (DXA) being the gold standard. We retrospectively included 1236 participants aged 50 years or above and who completed both DXA and routine chest CT scans within 6 months. Receiver operation characteristic (ROC) analysis was used to evaluate the diagnostic performance in detecting low bone mass and osteoporosis. Among 15,007 vertebrae analyzed, CT_AV at the 1st-12th thoracic (T1-T12) and the 1st lumbar (L1) vertebrae exhibited good discrimination for low bone loss and osteoporosis with the area under the ROC curve exceeding 0.80. Notably, T8 was the only vertebra to achieve sensitivity above 0.80 for both conditions: a cut-off value of 163.5 Hu yielded 81% sensitivity and 84% specificity for low bone mass, while 132.3 Hu yielded 82% sensitivity and 75% specificity for osteoporosis. These findings indicated that OC-CT demonstrated comparable diagnostic performance to DXA for bone mass evaluation in individuals aged 50 years or above. T8 was recommended as the optimal vertebral level for opportunistic bone mass evaluation, and T7 and T10 vertebrae were the preferred alternatives when T8 was not available. We also provided a user-friendly self-check table for rapid bone mass evaluation to facilitate clinical utility.

Axial spondyloarthritis (axSpA) is a chronic inflammation disorder commonly associated with osteoporosis and fractures. For further information about the pathophysiology of the latter, we analyzed transiliac biopsy samples from n = 21 men with axSpA (age 46 ± 6 years, mean ± SD). This cohort comprised patients with (GROUP-1, n = 5) or without increased osteoid thickness and mineralization lag time by histology (GROUP-2, n = 16). We performed quantitative backscattered electron imaging for bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS), and Raman microspectroscopy for bone material/compositional properties in cancellous (Cn.) and cortical (Ct.) bone compartments. Patients' outcomes were compared to different respective reference (REF)/control (CTRL) data. The total cohort and subgroup GROUP-1 (considered separately) showed significant deviations in BMDD versus REF. The average degree of cancellous bone mineralization was decreased by - 1.8% (p < 0.05) in the total cohort and decreased by - 5.1% (p < 0.01) in GROUP-1, while GROUP-2 had normal BMDD. The total cohort and both subgroups showed abnormal osteocyte OLS-characteristics. Specifically, the respective increases in OLS-area in cancellous and cortical bone were + 14.4% and + 44.5% in GROUP-1 and + 8.8% and + 24.9% in GROUP-2. The total cohort as well as both subgroups showed additionally deviations in organic matrix properties from CTRL with an increased pyridinoline content versus CTRL in both the cohort and subgroups. Our findings showed abnormal bone matrix mineralization in these patients with axSpA, with the largest deviations in the subgroup with histologically defined mineralization defects. The also observed altered osteocyte morphology and pyridinoline content might suggest osteocyte and osteoblast functional abnormalities in axSpA.

Sarcopenia, characterized by progressive loss of muscle mass, strength, and function, significantly impacts patient outcomes. Accurate assessment of muscle mass is essential for its diagnosis. Currently the agreement on how to use imaging for sarcopenia detection is still debated and how well the muscle imaging assessments correlate with muscle function needs further agreement. Recognizing the critical role of imaging in this process, the China National Center for Orthopedics (NCO) and the East Meets West Action Group of European Calcified Tissue Society (ECTS) convened a working group endorsed by the Board of the ECTS. This paper aims to evaluate the utility of various imaging techniques for diagnosing sarcopenia and understanding its functional consequences. We synthesize evidence on DXA, BIA, CT, MRI and ultrasound, and provide specific related recommendations. Imaging cannot replace functional assessments, but may enhance them by revealing subclinical disease, clarifying pathophysiology, and enabling individualized care. We hope to assist clinicians and researchers in using imaging to improve sarcopenia diagnosis, prognosis, and therapeutic monitoring, while also advocating for evidence-based structural and functional criteria in future guidelines.

Fibrous dysplasia/McCune-Albright (FD/MAS) syndrome is a rare bone disorder with a broad clinical manifestation. Pain is the most frequently reported complaint and can significantly impair quality of life. While most existing data are cross-sectional, little is known about symptom progression over time. This study aimed to assess changes in pain and QoL over 2 years follow-up. Patients in the PROFID study completed yearly questionnaires aligned with check-ups or independently if check-ups were less frequent. At baseline, 143 (85.6%) reported pain, of which 38 (26.6%) mild, 105 (73.4%) moderate/severe pain, and 24 (14.4%) had no pain. Emotional wellbeing and energy/fatigue were the most affected in the SF-36 domains. Patients viewed their disease as chronic, with moderate daily fluctuation and impact showed that active and palliative coping were the most frequently used coping mechanism. After 2 years, 27.4% of those with no or mild pain at baseline reported a significant increase in pain (1.3-5.0, p < 0.001), while scores in the moderate/severe group remained stable (6.6-6.3, p = 0.5). Emotional wellbeing improved significantly (37.6-55.5, p < 0.001). Patients with moderate/severe pain reported increased disease control, whereas those with no/mild pain felt less control (p = 0.01). Higher pain scores correlated with poorer physical (r = - 0.627), social (r = - 0.541), and general health (r = - 0.452), worse illness perceptions (e.g., illness identity r = 0.3), and greater palliative coping (r = 0.4), all p < 0.05. These findings emphasize the need to address both physical and psychological aspects of FD/MAS.

Type 2 diabetes (T2D) increases the risk of hip fracture, yet its global burden remains poorly quantified. This study assessed the association between T2D and hip fracture and estimated the worldwide T2D-attributable burden from 1990 to 2021, with projections to 2046. We updated a meta-analysis of PubMed, Embase, and Cochrane databases to estimate the pooled risk ratio (RR) for hip fracture in adults aged ≥ 40 with T2D. Combining the pooled RR with T2D prevalence and hip fracture data from the Global Burden of Disease study, we calculated the T2D-attributable population attributable fraction (PAF) and burden. Age-standardized incidence rate (ASIR), years lived with disability rate (ASYR), and average annual percentage change (AAPC) were assessed. Eleven studies (from 11,358 screened) indicated that T2D increased hip fracture risk by 34% (RR 1.34, 95% CI 1.17-1.54). In 2021, 4.70% (2.36-7.34) of incident hip fractures (≈950,200 cases) were attributable to T2D, over four times the 1990 estimate (≈200,180 cases). From 1990 to 2021, ASIR and ASYR rose globally, with the highest rates in high socio-demographic index (SDI) regions, particularly High-income North America. Women and older adults had higher burdens, though increases were faster in men. Projections suggest continued global ASIR (AAPC 0.50%) and ASYR (AAPC 0.07%) growth through 2046. T2D significantly contributes to the global hip fracture burden, especially in high-SDI regions. The persistent sex and age disparities underscore the need for targeted prevention strategies in high-risk populations.

Meclizine has been shown to promote bone growth by inhibiting a key signaling pathway involved in achondroplasia (ACH). Earlier studies demonstrated its safety in children with ACH after short-term use. The purpose of this study is to assess the safety and efficacy of meclizine treatment over 26 weeks in children with ACH. This open-label, single-arm, Phase 2 study was conducted at four sites in Japan. Nine children with ACH, aged 5-10 years old, received daily meclizine (12.5 mg/day for those < 20 kg; 25 mg/day for those ≥ 20 kg). This was co-administered with growth hormone therapy for 26 weeks. Safety was monitored through adverse events (AEs), while treatment efficacy was measured by changes in height velocity (cm/year). Secondary measures included the proportion of children achieving a height velocity of ≥ 6 cm/year and changes in arm span growth. Arm span velocity and the proportion of participants reaching ≥ 6 cm/year were evaluated through ad hoc analyses. No serious AEs were reported. Height velocity increased slightly from 4.35 ± 1.36 cm/year pre-treatment to 4.46 ± 1.54 cm/year post-treatment. One participant achieved a height velocity of ≥ 6 cm/year. Mean height increased from 107.48 ± 9.04 to 109.77 ± 8.69 cm over the study period. By contrast, arm span velocity was higher at 6.93 ± 2.50 cm/year, with six children reaching ≥ 6 cm/year. An additive effect of meclizine and growth hormone on promoting height was not observed; however, meclizine may enhance arm span growth in children with ACH.Trial registration number jRCT2041230001.

Introduction: Osteogenesis imperfecta (OI) is a rare disorder causing multiple fractures throughout life. No treatment has been shown to reduce the risk of fractures in OI. Here, we present the baseline characteristics of participants in the Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid (TOPaZ) trial. The aim of the trial is to determine whether teriparatide and zoledronic acid are superior to standard care in reducing the risk of clinical fractures.

Methods: We summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.

Results: We recruited 350 adults with a clinical diagnosis of OI in 27 European referral centres between June 2017 and October 2022. Overall, 266 (76.2%) had type I OI, 55 (15.8%) had type IV, and 19 (5.4%) had type III. The type was unknown in 9 (2.6%). Blue sclera were noted in 80.8%, and 35.8% had dentinogenesis imperfecta. Bisphosphonates had been administered to 28.1% in the 2 years prior to enrolment. Pathogenic variants in COL1A1 or COL1A2 were found in 87.6%. Fractures occurring in the 2 years prior to enrolment were not associated with bone density.

Conclusions: The TOPaZ population represents a unique cohort with which to study the genetic epidemiology and outcome of OI in relation to bone density and biochemical markers of bone turnover. When the trial reports, it will also provide new insights into the effect of an anabolic therapy, followed by antiresorptive treatment in the management of OI.

Public health problems regarding the potential association between Parkinson's disease (PD) and the increased prevalence of osteoporosis have been raised. However, the exact relationship, as well as potential treatment strategies, remains unclear and requires further investigation. Melatonin (MLT) is known for its beneficial effects on bone metabolism and its strong neuroprotective properties. Therefore, this study aimed to evaluate the potential role of MLT in the prevention and treatment of bone loss associated with PD using an hemiparkinsonian rat model induced by the destruction of dopaminergic neurons following intracerebral injection of 6-hydroxydopamine (6-OHDA). Forty male Wistar rats were divided into 5 groups: Control (CTR), 6-OHDA, MLT, 6-OHDA + MLT 1, and 6-OHDA + MLT 15. MLT (20 mg/kg/day) was administered intraperitoneally from Day 1 or Day 15, depending on the group. The effects on locomotor performance, oxidative status, bone structure, collagen accumulation, mineralization and the expression of bone marker proteins and genes were examined. Our results showed that the degeneration of dopaminergic neurons caused by 6-OHDA significantly impaired locomotor performance and induced marked alterations in bone parameters. Early MLT treatment (Day 1) mitigated these bone alterations by preserving structural integrity, enhancing collagen accumulation, and modulating bone marker expression. Importantly, beneficial effects on bone were also observed when MLT was administered later (Day 15), despite the absence of significant improvement in motor deficits. These findings suggest that dopaminergic neuron degeneration can negatively influence bone health and that MLT may exert a direct osteoprotective effect, supporting its possible therapeutic utility in managing bone fragility associated with PD.