Calcified Tissue International最新文献

This retrospective cross-sectional study investigated the diagnostic performance of four magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring methods for identifying osteoporosis in postmenopausal women and explored the impact of MRI system variability, using quantitative computed tomography (QCT) as the reference standard. A total of 181 women who underwent lumbar spine QCT and MRI within a six-month interval were included. VBQ scores were calculated from routine sagittal T1-weighted images. Diagnostic performance was assessed using receiver operating characteristic curve analysis, correlations with QCT-derived bone mineral density (BMD) were evaluated using Spearman's correlation, and agreement and inter-method variability were analyzed using appropriate comparative and agreement analyses. All four VBQ scoring methods demonstrated moderate diagnostic performance, with areas under the curve ranging from 0.739-0.783, and showed moderate negative correlations with BMD (R = - 0.488 to - 0.549). Significant differences were observed among VBQ scoring methods (p = 0.018) and across MRI systems from different vendors (p < 0.001). An optimal cutoff value of VBQ > 4.0 was identified using the Youden index. These findings suggest that MRI-derived VBQ scoring may serve as a useful, radiation-free, opportunistic adjunct for osteoporosis assessment in postmenopausal women undergoing lumbar MRI for other clinical indications. However, the observed inter-method and inter-scanner variability highlights the need for further standardization of VBQ scoring approaches and MRI acquisition protocols before broader clinical implementation.

Bone metabolism is a dynamic process regulated by systemic and local factors, including sex hormones. While in vitro studies suggest that hormonal fluctuations impact bone biomarkers, in vivo findings remain inconsistent. Therefore, this systematic review aimed to evaluate whether biochemical markers of bone resorption and bone formation fluctuate across different phases of the menstrual cycle in healthy regular menstruating females. Following PRISMA guidelines, a comprehensive search was conducted in PubMed and Web of Science (January 2025). A total of 18 studies were included and assessed for quality using the NHLBI Quality Assessment Tool. Considerable heterogeneity was found across studies in design, phase classification, and outcome reporting. While 5 out of 7 studies on β-CTX-I reported lower concentrations during the luteal phase, 6 out of 8 studies showed that osteocalcin concentrations did not vary across the MC. Findings concerning other biomarkers included in this review were limited and inconsistent, hindering the identification of a clear trend. Current evidence does not establish a consistent pattern in bone metabolism biomarker fluctuations across the MC. Variability in methodology, hormone verification, and participant characteristics may contribute to these inconsistencies.PROSPERO registration CRD42022375821.

Osteoporosis is characterized by an imbalance in bone remodeling, resulting in bone loss and increased fracture risk. Inflammatory diseases, such as rheumatoid arthritis, are strongly associated with secondary osteoporosis due to inflammation-induced bone loss. Pro-inflammatory cytokines, particularly TNF-α, disrupt bone homeostasis by promoting osteoclastogenesis and inhibiting osteoblast function. The Wnt signaling pathway is essential for bone formation and is suppressed in inflammatory conditions. WNT16, an osteoblast-derived ligand, increases bone mass mainly by inhibiting osteoclast differentiation but has also been found to stimulate osteoblast activity. Here we demonstrate that TNF-α downregulates Wnt16 mRNA expression in primary osteoblasts, suggesting that inflammation may impair WNT16 expression and thereby reduce bone mass. To evaluate whether pharmacological or genetical elevation of WNT16 levels can mitigate inflammation-induced bone loss, we examined the effect of WNT16 in three mouse models of local and systemic inflammation. In a knee arthritis model, intra-articular delivery of WNT16 liposomes failed to prevent local bone loss. Similarly, although osteoblast-specific WNT16 overexpression increased the overall bone mass, it did not protect against either local calvarial bone loss or systemic bone loss induced by Toll-like receptor 2 (TLR2) activation. Furthermore, in a model of systemic inflammation induced by Staphylococcus aureus, WNT16 overexpression did not preserve vertebral trabecular bone, despite increased baseline bone mass. These findings demonstrate that WNT16, although increasing the overall bone mass, is insufficient to counteract inflammation-driven bone loss.

Osteogenesis imperfecta is a rare hereditary condition affecting type 1 collagen formation. Among the wide spectrum of phenotypic features, osteogenesis imperfecta variably impairs craniofacial growth, affecting facial morphology and predisposing to malocclusion. At present, bisphosphonates are the gold standard for treatment of osteogenesis imperfecta, but knowledge on the effect of the medication on craniofacial growth is lacking. This retrospective study analysed lateral skull radiographs of 36 growing individuals with osteogenesis imperfecta and bisphosphonate treatment history (mean age 10.0 years, 13 females). Of them, 23 had been diagnosed with type I, 8 with type III, and 5 with type IV osteogenesis imperfecta. The historical control group that had not received bisphosphonate therapy comprised 34 individuals (mean age 8.1 years, 22 females) with osteogenesis imperfecta, type I in 18, type III in 7, and type IV in 9 individuals. The cephalometric measurement values were converted into age- and sex-matched Z-scores based on normal population values of the same ethnicity. Inter-group comparisons of the Z-scores showed several statistically significant differences where the bisphosphonate treatment group deviated less from unaffected population than the historical group. These included one or more of the mandibular size measurements in all studied types of osteogenesis imperfecta, anterior facial height and maxillary length in type IV, as well as cranial base angle, posterior facial height and angulation between the jaws in type III. Our findings suggest that bisphosphonate therapy may positively enhance both mid-facial and mandibular craniofacial growth in individuals with osteogenesis imperfecta.

Cxcr2 is a chemokine receptor involved in immune cell trafficking, inflammation, and wound healing that has been implicated in multiple diseases and cancers. However, there is a relative lack of knowledge of the in vivo functions of Cxcr2 in bone cell biology. Here we characterized the skeletal and hematological phenotypes of Cxcr2-deficient mice (Cxcr2 KO) backcrossed onto the FVB/N background. Structural and biomechanical testing demonstrated that Cxcr2 KO caused a significant loss of trabecular and cortical bone volume, altered bone geometry, and an associated loss of bone strength relative to controls. Histological analysis suggests that this is a consequence of increased osteoclast activity in Cxcr2 KO mice, while osteoblasts were not affected. Serum analysis revealed elevated levels of the bone resorption marker CTX-1, with no change in the bone formation marker P1NP, suggesting a shift towards increased osteoclast-mediated bone turnover. While both RANKL and OPG were decreased in Cxcr2 KO bones, the RANKL/OPG ratio was not different compared to WT mice. Additionally, Cxcr2 KO mice displayed systemic immune dysregulation, including elevated serum cytokines and altered hematological parameters, fewer megakaryocytes in bone marrow, higher neutrophil counts in blood, and anisocytosis. Our data point to Cxcr2 as a critical and multifunctional regulator of healthy bone homeostasis, linking immune function with skeletal integrity. This work highlights the Cxcr2 KO model as a valuable system for studying inflammatory bone loss and osteoimmunological interactions.

Background: Chronic kidney disease (CKD) impacts a large and growing proportion of the population. Fracture rates are high in individuals with CKD compared to the non-CKD population. Dietary patterns consisting of higher fat and sugar intake are associated with higher risk of developing CKD, but the impact of different dietary patterns on the skeleton in the setting of CKD is largely unknown.

Objective: To assess the impact of a high fat/high sucrose diet (HFHS) in male Sprague Dawley rats with adenine-induced CKD (Ad).

Methods: Rats were given the HFHS or standard diet (SD) for 4 weeks followed by 8 weeks with adenine incorporated into those diets for the Ad groups.

Results: All Ad rats, regardless of diet, had high circulating blood urea nitrogen and parathyroid hormone (PTH). Ad + SD rats had greater femoral volumetric cortical porosity and pore number and lower mechanical properties than Ad + HFHS rats. Ad + HFHS had a lower percentage of cortical bone osteocytes positive for PTHR1 and RANKL matching trends in porosity; however, the HFHS diet led to greater TNF-α-positive osteocytes and trabecular osteoclast numbers.

Conclusions: There were differences in the skeletal response to adenine-induced CKD based on diet with the standard diet leading to a skeletal phenotype more associated with high PTH. These data demonstrate both the complexity of systemic alterations impacting bone in CKD and highlight the importance of understanding the influence of dietary factors on skeletal outcomes.