Calcified Tissue International最新文献

Studies evaluating habitual dietary copper intake and bone mineral density have garnered significant interest due to copper's indispensable role in collagen cross-linking and osteogenesis. These investigations, which employ dietary assessment tools alongside DXA measurements of skeletal sites, have nonetheless yielded heterogeneous results regarding the impact of copper consumption on bone health. Consequently, elucidating the nature and magnitude of this association is of paramount importance for both nutritional epidemiology and osteoporosis prevention. The review was conducted in accordance with PRISMA guidelines and registered in Prospero (CRD42024617075). Electronic literature searches were performed up to February 2025 in EMBASE, PubMed, OVID, Scopus, and Web of Science to identify observational studies assessing dietary copper intake and DXA-measured BMD, and study quality was appraised using the Newcastle-Ottawa Scale. Data were pooled via a generic inverse-variance random-effects model, with heterogeneity assessed by the Q test and I² statistic. A random-effects meta-analysis of three studies (n = 9059) found that higher dietary copper intake was associated with a modest but significant increase in lumbar spine BMD (MD 0.02 g/cm²; 95% CI 0.00-0.04; p = 0.04; I² = 36%), whereas a separate meta-analysis of four studies (n = 14,345) for hip BMD showed a similar MD of 0.02 g/cm² that did not reach significance (95% CI - 0.00-0.04; p = 0.07; I² = 74%). Higher dietary copper intake is modestly associated with increased lumbar spine BMD, while evidence for hip BMD remains inconclusive, underscoring copper's potential role in osteoporosis prevention.

This study assessed the effect of cellular senescence-related genes in the development of osteoporosis (OP) via the databases, which may be the potential targeted biomarkers of the OP. The development of OP is significantly influenced by cellular senescence (CS). However, the exact mechanism of CS in OP is unknown. Hence, it is imperative to uncover the molecular mechanisms and therapeutic targets implicated in CS-associated OP. In the Gene Expression Omnibus (GEO) and GeneCards databases, we identified differential genes (DEGs) that are associated with OP and CS. Subsequently, their function was assessed through GO, KEGG, and GSEA analysis. The protein-protein interaction (PPI) network was correlated and analyzed to obtain key genes. Finally, animal models were employed for experimental validation. Eight genes, CDK1, CCNB1, TOP2A, FEN1, CDC6, FOXM1, CDC25A, and MCM2, were recognized as potential biomarker genes. FEN1 and CDC6, as new potential markers, have not been reported yet. We found that cell cycle regulation has an important role in aging-induced OP, which provides new ideas for the further development of targeted therapies.

Osteogenesis imperfecta (OI) is a group of rare, hereditary diseases caused by mutations to the genes involved in the biosynthesis of collagen type 1. A cardinal feature of OI is the frequent occurrence of fractures. Individuals with OI often experience pain that is not related to fracture episodes. However, little is known about the use of analgesics among people with OI. We aim to examine the use of analgesics in Danes with OI as a measure of pain, using register-based data. This study is a Danish nationwide, population-based, and register-based cohort study. It includes all individuals registered with an OI diagnosis from January 1977 to December 2018, and a reference population matched by birth month, year, and sex. We examined the number of prevalent analgesic users over time and by age, the amount of analgesic use in Defined Daily Doses (DDDs), and the risk of initiating analgesics as well as treatment at a specialised pain centre during the observation period. We present the Sub Hazard Ratio (SHR) [95% confidence interval] for the endpoints comparing the OI cohort to the reference population. Lastly, we evaluated the changes in analgesic use related to fractures in the OI cohort and the proportion of long-term opioid users in both cohorts. A total of 905 individuals with OI and 4542 in the reference population were identified. There were more prevalent analgesic users (71.8% vs. 46.8%) in the OI cohort, with the number of users increasing over time and with age. Individuals in the OI cohort were more likely to initiate analgesics (SHR 1.86 [1.68-2.05]) and specialised pain care (SHR 5.8 [3.1-11.0]) than in the reference cohort. The use of analgesics, as measured in total DDDs, increased shortly after a fracture in the OI cohort but normalised to pre-fracture levels within 6 months. A higher proportion of the OI cohort had repeated dispensed prescriptions of opioids compared to the reference population. Individuals with OI are more likely to use analgesics and to use more analgesics-as measured by DDDs-than non-OI individuals.

Methylphenidate (MP) is widely prescribed for attention-deficit/hyperactivity disorder in children and adults. Concerns have emerged regarding its potential effects on bone health, including changes in bone mineral density, fracture risk, and size. However, its effects on skeleton remains controversial. This systematic review and meta-analysis aimed to clarify whether MP administration affects bone health in animal models. Our review was registered with PROSPERO (CRD 42023468466) following PRISMA guidelines. A comprehensive search of MEDLINE, Embase, Scopus, and CINAHL was conducted through May 2025, with no restrictions on year or language. Eight studies from 508 identified articles met the inclusion criteria after full-text screening. These studies compared the effects of different doses of MP on bone morphology, biomechanical properties, microarchitecture, and histomorphometric endpoints in rats' axial and appendicular skeletons. The studies also compared the effects of age at initiation of MP treatment and different durations of MP treatment. Overall, a trend emerged indicating that MP may exert detrimental effects on various bone parameters, particularly in long bones, with age at MP treatment initiation and dose- and duration- dependent responses. Additionally, MP treatment may influence bone tissue directly, through actions on bone cells, and indirectly, through changes in body weight. Meta-analyses revealed significant adverse effects on bone morphology and mechanical properties, especially with higher doses and prolonged exposure. However, the overall risk of bias ranged from unclear to high across included studies, requiring caution in interpretation. The findings emphasize the need for further research into the mechanisms behind MP's impact on bone, including age at MP treatment initiation and treatment duration, dose-response relationships, and sex differences. Better understanding of the metabolic pathways which influence MP's effects on the above endpoints could clarify broader implications of MP use on skeletal health and inform clinical practices.

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.