Calcified Tissue International最新文献

Introduction: Male idiopathic osteoporosis (MIO), defined as primary osteoporosis with unclear etiology in men, is characterized by low bone mass and increased fracture risk. The underlying pathophysiology remains poorly understood, particularly regarding bone microstructure, turnover, and mineralization.

Purpose: To characterize bone material properties in men with idiopathic osteoporosis using histomorphometry, bone mineralization analysis, and osteocyte lacunae morphology.

Methods: Transiliac bone biopsies from 20 men with idiopathic osteoporosis (mean age 46.5 ± 12.1 years) were analyzed after exclusion of secondary causes. Undecalcified PMMA-embedded samples were assessed for static and dynamic histomorphometric parameters. Dynamic bone formation was evaluated using tetracycline double labeling. Quantitative backscattered electron imaging determined bone mineralization density distribution in cortical and trabecular compartments and osteocyte lacunae section characteristics.

Results: Compared with age-matched reference data, patients exhibited significantly reduced trabecular bone volume fraction (p = 0.007), thickness (p = 0.003), and number (p = 0.03), alongside decreased osteoid thickness (p < 0.001) and osteoblast surface (p = 0.002). Dynamic analysis revealed lower adjusted apposition rate (p = 0.003) and prolonged mineralization lag time (p = 0.007), indicating low bone turnover. Trabecular bone mineralization was reduced, with lower CaMean (p = 0.001), CaPeak (p < 0.001), and CaHigh (p = 0.007), and higher CaLow (p = 0.02). Cortical mineralization remained normal, although cortical width was decreased (p = 0.044). Osteocyte lacunar aspect ratio was significantly reduced in cortical and trabecular bone (both p < 0.001), while lacunar density and area were unchanged.

Conclusion: Men with idiopathic osteoporosis present a distinct skeletal phenotype characterized by compromised trabecular microarchitecture, suppressed bone formation, and selective trabecular hypomineralization, despite preserved cortical mineralization. These findings suggest that MIO represents a low-turnover bone disorder with impaired mineralization kinetics.

Pain is the most common symptom of Paget's disease of bone (PDB), but its underlying mechanisms are poorly understood. Notably, bone pain does not correlate well with metabolic activity or treatment response. This study aimed to assess whether sensory processing is altered in skin overlying Pagetic bone using quantitative sensory testing (QST). We conducted a cross-sectional study of 156 people with PDB attending secondary care referral centres in the UK. We conducted quantitative sensory testing of the skin overlying affected sites and compared the data with unaffected sites as a control. The modalities used were hot and cold rollers, pinprick, vibration and von-Frey filaments to test both spinothalamic and lemniscal pathways. There was a consistent trend for sensory perception to be increased over affected sites versus control sites in the study population. The differences were significant for vibration detection threshold (p = 0.009), pain threshold (p = 0.010) and both single and multiple pinprick testing methods (both p < 0.001). Subgroup analysis revealed similar trends when analysis was restricted to those with pain thought to be due to bone deformity or increased metabolic activity and those with and without musculoskeletal pain. Sensory processing is altered in skin overlying Pagetic bone, independent of current pain symptoms. We speculate that this may be due to abnormalities of bone shape, bone structure or metabolic abnormalities in the affected bone. The mechanisms are unclear but deserve further study.

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.