Calcified Tissue International最新文献

To explore the hypothesis that knee osteoarthritis patients with osteoporosis represent a sub-cohort with different disease characteristics and origin of symptoms. Men and women in the Osteoarthritis Initiative (OAI) at visit 5 (36 months) were examined for osteoporosis (N = 1483) using DXA (T-score at femoral neck ≤ -2.5), use of bisphosphonates, or having experienced a fracture. Those with and without osteoporosis were compared by subchondral bone quality, bone marrow lesion (BML) properties, and cartilage thickness from MRI, with general linear modeling. Relationships between symptoms (12 months later) and each of cartilage or subchondral bone features were examined conditional on osteoporosis status. Overall, 15.2% of 1246 participants (825 women, 658 men, mean age: 64.4 ± 8.9yrs, BMI: 30.1 ± 4.9 kg/m²) with knee OA likely had osteoporosis and showed lower medial and lateral subchondral bone density, smaller trabecular number and larger trabecular separation (all p < 0.01) compared to those without. Cartilage thickness appeared lower in this group (p = 0.04) but only by a small amount. Knee symptoms correlated with both BML properties and cartilage thickness; the latter but not the former being moderated by osteoporosis status. Those with osteoporosis showed no relationship between cartilage and knee symptoms, but demonstrated bone-related associations with symptoms. Osteoporosis affects the pattern of subchondral bone and cartilage properties in individuals with knee osteoarthritis. Knee symptoms in this subgroup likely originates in bone instead of cartilage. Osteoporosis screening may help identify knee osteoarthritis patients at further risk of subchondral bone damage leading to pain.

The present study aimed to assess bone strength and microstructure in patients with pseudohypoparathyroidism (PHP), nonsurgical HP (NS-HP), and healthy controls. A total of 54 PHP1 patients (14 PHP1a, 40 PHP1b), 54 age-/sex- matched NS-HP patients and 27 age-/sex-matched controls were enrolled. Clinical characteristics, biochemical indices and HR-pQCT indices were respectively collected. PHP1 patients had higher serum Ca and PTH level than NS-HP patients at the time of both diagnosis and HR-pQCT measurement. A higher BMI and lower serum P level were observed in PHP1 patients than NS-HP patients at the time of HR-pQCT measurement. Bone microstructure analysis showed PHP1 patients had decreased Tb.N, increased Tb.Sp, and increased Tb.1/N.SD at tibia compared to NS-HP patients. Subgroup analysis showed no significant difference in Tb.N and Tb.Sp in PHP1b patients compared to NS-HP patients. Multiple linear regression analysis showed increased Tb.N and decreased Tb.Sp at tibia were associated with longer treatment duration in PHP1b patients. The microarchitecture evaluated by HR-pQCT in this study further supported that bone tissue had a preserved sensitivity to PTH in PHP1 patients and trabecular bone was more susceptible. Moreover, at least, bone status in PHP1b patients might benefit from regular treatment.

The relationship between dietary tryptophan intake and the risk of low bone mineral density (LBMD) has not been thoroughly evaluated. This study aimed to examine the relationship between dietary tryptophan intake and LBMD. A total of 12,003 participants aged 50 years and older with complete data on bone mineral density (BMD) and tryptophan intake from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2020 were included in this cross-sectional study. The median dietary tryptophan intake among the 12,003 participants was 1822.14 mg/day, with significantly lower levels observed in individuals with LBMD compared to those with normal bone mass (1740.45 mg/day vs. 2041.39 mg/day, p < 0.001). For every 2.7-fold increase in dietary tryptophan intake, the risk of low BMD decreases by 22%. When dietary tryptophan intake was categorized into quartiles, significantly lower risks of LBMD were observed in the third [Odds Ratio (OR) = 0.68, 95% confidence interval (CI): 0.51-0.91] and fourth (OR = 0.65, 95% CI: 0.49-0.87) quartiles compared to the reference group after multivariable adjustment. Moreover, the restricted cubic spline (RCS) results revealed a negative nonlinear relationship between dietary tryptophan intake and LBMD (p for overall < 0.001, p for nonlinear < 0.05), with this correlation remaining consistent across various population subgroups and exhibiting no significant interaction according to stratification variables. Sensitivity analyses further substantiated these findings. Overall, we found that increased dietary tryptophan intake may be associated with a lower risk of LBMD among individuals aged ≥ 50 years, highlighting the importance of optimizing tryptophan nutrition for reducing osteoporosis risk.

Complications from anterior decompression fusion for cervical ossification of the posterior longitudinal ligament (OPLL) are often related to the bone mineral density (BMD) of vertebral bodies and ossified masses. The aim of this study was to clarify whether dual-energy X-ray absorptiometry (DEXA) T-scores reliably predict BMD in these structures, and whether vertebral bone quality (VBQ) and Hounsfield units (HU) can be effectively used to screen for osteopenia and osteoporosis. A total of 122 patients with cervical OPLL and 105 non-OPLL patients were included. Vertebral BMD was assessed by VBQ and HU, and ossified mass BMD was assessed by ossified mass bone quality (OMBQ) and ossification mass HU (OMHU). Overall, VBQ scores and HU values demonstrated weaker correlations with T-scores in the OPLL group compared with the non-OPLL group. Receiver operating characteristic curve analyses showed that VBQ and HU effectively discriminated osteopenia/osteoporosis in the OPLL cohort, with area under the curve values ranging from 0.763 to 0.827, similar to the non-OPLL. No significant differences in BMD were observed between the OPLL and non-OPLL groups based on the common assessment of VBQ, HU and DEXA-derived BMD (p > 0.05). Both OMBQ and OMHU showed good reliability and were significantly correlated with T-scores (p < 0.05). In patients with cervical OPLL, VBQ and HU remain effective screening tools for osteopenia/osteoporosis, potentially guiding or obviating the need for further DEXA scans. Additionally, our findings suggest that patients with lower T-scores may exhibit reduced BMD in both vertebral bodies and ossified masses.

Short and long sleep duration have been linked with adverse health outcomes. However, it is unclear if sleep duration affects the risk of low bone mineral density (BMD) or osteoporosis. We systematically reviewed evidence examining the association between short and long sleep with BMD/osteoporosis. PUBMED, Embase, CENTRAL, Web of Science, and Scopus were examined for studies up to July 15, 2024. We pooled adjusted odds ratio (OR) for the association between sleep and osteoporosis and adjusted linear regression coefficients (β) for BMD. A separate analysis was conducted for males, females, postmenopausal females, and the elderly. 14 studies were included. Three were cohort, while the rest were cross-sectional. The definition of short and long sleep varied among studies. Meta-analysis showed that long (OR 1.19 95% CI 1.05, 1.35 I² = 72%) but not short (OR 1.11 95% CI 0.95, 1.29 I² = 80%) sleep duration was associated with osteoporosis. Similar results were obtained for females and postmenopausal females. In males, both short and long sleep was associated osteoporosis while no such association was noted in the elderly. Meta-analysis showed that short sleep did not have any significant association with BMD (β - 0.002 95% CI - 0.007, 0.004 I² = 0), while long sleep duration was associated with a reduction in BMD (β - 0.017 95% CI - 0.031, - 0.004 I² = 0). Separate analyses for males and females revealed non-significant results. Evidence from mostly cross-sectional data suggests that long sleep duration may be a related to BMD and osteoporosis. Short sleep was not found to be related to BMD and osteoporosis, except for males where a significant effect was noted. Given the low-quality evidence, results must be interpreted with caution.

Hypophosphatemia resulting from intravenous iron treatment has become an increasingly concerning syndrome in recent years. We report the case of a 66-year-old male patient with a medical history of ankylosing spondylitis (AS), Crohn's disease, and chronic iron deficiency. Following intravenous iron infusions of ferric carboxymaltose, the patient developed diffuse bone pain and multiple bone fractures. After ruling out that the pain was in the context of spondyloarthritis (SpA), the diagnosis of osteomalacia associated with hypophosphatemia was established based on his clinical history, complementary analytical, and imaging tests. Once the diagnosis was made, intravenous ferric carboxymaltose infusions were discontinued, and oral calcium and vitamin D supplementation were initiated, resulting in clinical improvement with serum phosphate levels' normalization. This case shows the importance of recognizing the risk factors and clinical findings in selected patients, monitoring phosphate levels in those with high risk factors and considering stopping or switching to another intravenous iron formulation. Furthermore, this case highlights the importance of maintaining clinical suspicion of other possible etiologies of pain in patients with SpA.

Osteogenesis imperfecta (OI) is a heterogeneous heritable skeletal dysplasia characterized by bone fragility and deformity, growth deficiency, and other secondary connective tissue defects. OI is now understood as a collagen-related disorder caused by defects of genes whose protein products interact with collagen for folding, post-translational modification, processing and trafficking, affecting bone mineralization and osteoblast differentiation. This review provides the latest updates on genetics of OI, including new developments in both dominant and rare OI forms, as well as the signaling pathways involved in OI pathophysiology. There is a special emphasis on discoveries of recessive mutations in TENT5A, MESD, KDELR2 and CCDC134 whose causality of OI types XIX, XX, XXI and XXI, respectively, is now established and expends the complexity of mechanisms underlying OI to overlap LRP5/6 and MAPK/ERK pathways. We also review in detail new discoveries connecting the known OI types to each other, which may underlie an eventual understanding of a final common pathway in OI cellular and bone biology.

Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia characterized by high fracture rates and broad variations in clinical manifestations ranging from mild to increasingly severe and perinatal lethal forms. The underlying mutations affect either the synthesis or processing of the type I procollagen molecule itself or proteins that are involved in the formation and mineralization of the collagen matrix. Consequently, the collagen forming cells, the osteoblasts, become broadly dysfunctional in OI. Strikingly, hypermineralized bone matrix seems to be a frequent feature in OI, despite the variability in clinical severity and mutations in the so far studied different forms of human OI. While the causes of the increased mineral content of the bone matrix are not fully understood yet, there is evidence that the descendants of the osteoblasts, the osteocytes, which play a critical role not only in bone remodeling, but also in mineralization and sensing of mechanical loads, are also highly dysregulated and might be of major importance in the pathogenesis of OI. In this review article, we firstly summarize findings of cellular abnormalities in osteoblasts and osteocytes, alterations of the organic matrix, as well as of the microstructural organization of bone. Secondly, we focus on the hypermineralization of the bone matrix in OI as observed in several different forms of human OI as well as in animal models, its measurement and potential mechanical implications and its effect on the bone mineral density measured by dual X-ray absorptiometry. Thirdly, we give an overview of established medication treatments of OI and new approaches with a focus of their known or possible effects on the bone material, particularly on bone matrix mineralization.

In the last decades, the easy genetic manipulation, the external fertilization, the high percentage of homology with human genes and the reduced husbandry costs compared to rodents, made zebrafish a valid model for studying human diseases and for developing new therapeutical strategies. Since zebrafish shares with mammals the same bone cells and ossification types, it became widely used to dissect mechanisms and possible new therapeutic approaches in the field of common and rare bone diseases, such as osteoporosis and osteogenesis imperfecta (OI), respectively. OI is a heritable skeletal disorder caused by defects in gene encoding collagen I or proteins/enzymes necessary for collagen I synthesis and secretion. Nevertheless, OI patients can be also characterized by extraskeletal manifestations such as dentinogenesis imperfecta, muscle weakness, cardiac valve and pulmonary abnormalities and skin laxity. In this review, we provide an overview of the available zebrafish models for both dominant and recessive forms of OI. An updated description of all the main similarities and differences between zebrafish and mammal skeleton, muscle, heart and skin, will be also discussed. Finally, a list of high- and low-throughput techniques available to exploit both larvae and adult OI zebrafish models as unique tools for the discovery of new therapeutic approaches will be presented.