Calcified Tissue International最新文献

Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.

Lipid accumulation product (LAP) has a positive effect on spinal bone mineral density (BMD). However, once LAP levels exceed 27.26, the rate of spinal BMD increase slow down or even decline. This indicates a biphasic relationship between lipid metabolism and BMD, suggesting potential benefits within a certain range and possible adverse effects beyond that range. This study aimed to investigate the potential association between LAP index and BMD in US adults, as well as to explore the presence of a potential saturation effect in this relationship. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. A multiple stepwise regression model was employed to examine the association between LAP index and total spinal BMD. Additionally, a generalized additive model and a smooth curve fitting algorithm were utilized to examine the relationship, and saturation effect study was conducted to determine the saturation level. The calculation formula of LAP used in the study was: (LAP = (waist circumstances (WC) (cm) - 58) × triglyceride (TG) (mmol/L)) for women, and (LAP = (WC (cm) - 65) × TG (mmol/L)) for men. The study involved a total of 7913 participants aged 20 years or older. Through multiple stepwise regression analysis, it was found that individuals with higher LAP scores exhibited higher total spinal BMD. In both the crude and partially adjusted models, total spinal BMD was significantly higher in the highest LAP quartile (Q4) compared to the lowest LAP quartile (Q1) (P < 0.05). Utilizing a generalized additive model and smooth curve, a nonlinear relationship between LAP and total spinal BMD was observed. Furthermore, the study identified the saturation value of LAP to be 27.26, indicating a saturation effect. This research highlights a nonlinear relationship between LAP and total spinal BMD, along with the presence of a saturation effect.

Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40-0.83; p < 0.0001; I² = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term.

Rare diseases (RDs) bear a significant challenge to individuals, healthcare systems, and societies. The European reference network on Rare BONe diseases (ERN BOND) is committed to improving multidisciplinary, patient-centred care for individuals with rare bone and mineral diseases (RBMDs). Its affiliated project, the European registries for rare bone and mineral conditions (EuRR-Bone) collects data using two different platforms, an electronic surveillance system (e-REC) that captures the occurrence of RBMDs and the Core Registry, a platform with the infrastructure for collecting Core data fields and longitudinal generic and condition-specific information. With emerging registries and the overlap with other ERNs, it is key to maintain the capability of the platforms to adapt to the needs of the network and the community whilst adhering to quality and FAIR (findable, accessible, interoperable, and reusable) principles. This binomial ensures long-term sustainability and potential advances in the care pathway of RBMDs whilst promoting good practice standards within Europe and beyond.

The lacunocanalicular network (LCN) is an intricate arrangement of cavities (lacunae) and channels (canaliculi), which permeates the mineralized bone matrix. In its porosity, the LCN accommodates the cell network of osteocytes. These two nested networks are attributed a variety of essential functions including transport, signaling, and mechanosensitivity due to load-induced fluid flow through the LCN. For a more quantitative assessment of the networks' function, the three-dimensional architecture has to be known. For this reason, we aimed (i) to quantitatively characterize spatial heterogeneities of the LCN in whole mouse tibial cross-sections of BALB/c mice and (ii) to analyze differences in LCN architecture by comparison with another commonly used inbred mouse strain, the C57BL/6 mouse. Both tibiae of five BALB/c mice (female, 26-week-old) were stained using rhodamine 6G and whole tibiae cross-sections were imaged using confocal laser scanning microscopy. Using image analysis, the LCN was quantified in terms of density and connectivity and lacunar parameters, such as lacunar degree, volume, and shape. In the same tibial cross-sections, the calcium content was measured using quantitative backscattered electron imaging (qBEI). A structural analysis of the LCN properties showed that spatially denser parts of the LCN are mainly due to a higher density of branching points in the network. While a high intra-individual variability of network density was detected within the cortex, the inter-individual variability between different mice was low. In comparison to C57BL/6J mice, BALB/c mice showed a distinct lower canalicular density. This reduced network was already detectable on a local network level with fewer canaliculi emanating from lacunae. Spatial correlation with qBEI images demonstrated that bone modeling resulted in disruptions in the network architecture. The spatial heterogeneity and differences in density of the LCN likely affects the fluid flow within the network and therefore bone's mechanoresponse to loading.

Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4-5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003-1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000-1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180-1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD.

Cementum is the least studied of all mineralized tissues and little is known about mechanisms regulating its formation. Therefore, the goal of this study was to provide new insights into the transcriptional regulation of cementum formation by determining the consequences of the deficiency of the Trps1 transcription factor in cementoblasts. We used Trps1^Col1a1 cKO (2.3Co1a1-Cre^ERT2;Trps1^fl/fl) mice, in which Trps1 is deleted in cementoblasts. Micro-computed tomography analyses of molars of 4-week-old males and females demonstrated significantly shorter roots with thinner mineralized tissues (root dentin and cementum) in Trps1^Col1a1 cKO compared to WT mice. Semi-quantitative histological analyses revealed a significantly reduced area of cellular cementum and localized deficiencies of acellular cementum in Trps1^Col1a1 cKO mice. Immunohistochemical analyses revealed clustering of cementoblasts at the apex of roots, and intermittent absence of cementoblasts on Trps1^Col1a1 cKO cementum surfaces. Fewer Osterix-positive cells adjacent to cellular cementum were also detected in Trps1^Col1a1 cKO compared to WT mice. Decreased levels of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme required for proper cementogenesis, were apparent in cementum, periodontal ligament, and alveolar bone of Trps1^Col1a1 cKO. There were no apparent differences in levels of bone sialoprotein (Bsp) in cementum. Quantitative analyses of picrosirius red-stained periodontal ligament revealed shorter and disorganized collagen fibers in Trps1^Col1a1 cKO mice demonstrating impaired periodontal structure. In conclusion, this study has identified Trps1 transcription factor as one of the important regulators of cellular and acellular cementum formation. Furthermore, this study suggests that Trps1 supports the function of cementoblasts by upregulating expression of the major proteins required for cementogenesis, such as Osterix and TNAP.

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4 years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable.

Fermented dairy products have recently gained popularity due to their purported health benefits, nevertheless, their role in ageing remains uncertain. This narrative review aims to evaluate evidence from observational (prospective) and interventional studies on the potential benefits of fermented dairy product consumption for musculoskeletal and mental health in older adults. Additionally, it seeks to determine whether any observed benefits surpass those of non-fermented dairy products and to identify directions for future research. Prospective studies support either favourable or neutral associations of fermented dairy products with outcomes of musculoskeletal health or neutral associations with mental health outcomes, whilst it remains unclear if the benefits observed with fermented dairy products go beyond those of the non-fermented dairy foods. Few interventional studies suggest overall favourable effects of yogurt and cheese on musculoskeletal health in older adults but given their small number (N = 6) and heterogeneity, they do not allow a clear assessment or definitive recommendations for fermented dairy intake. Interventional studies reporting mental health outcomes are largely lacking for this age group (N = 1). Given the very limited evidence for the effectiveness of fermented dairy products, future well-designed prospective and randomized controlled trials are needed to better understand their benefits (especially compared to those of non-fermented dairy foods), their characteristics and the quantities required to offer protection against musculoskeletal and/or mental health ageing.