Calcified Tissue International最新文献

The purpose of this study was to determine if a 6-week 20% caloric restrictive (CR) diet, with or without resistance training, would impact bone health in growing young female rats. Forty female rats (~ 5 wks old) were randomly divided into the following groups: baseline (n = 8), sedentary fed a normal diet (N, n = 8), sedentary fed a 20% CR diet (D, n = 8), resistance trained fed a normal diet (NT, n = 8), and resistance trained fed a 20% CR diet (DT, n = 8). The exercise groups were conditioned to climb a vertical ladder 4 consecutive times (per exercise session) with weights appended to their tail 3 days/wk for a total of 6 wks. Tibial bone mineral density (BMD) was assessed via dual-energy x-ray absorptiometry scans. After 6 wks, the body mass (mean ± SD) for CR fed groups (D = 232.6 ± 26.3 g & DT = 216.6 ± 17.9 g) were significantly lower than the normal fed groups (N = 266.1 ± 31.5 g & NT = 251.9 ± 23.4 g). Tibial BMD (in g/cm²) for the sedentary CR group (D = 0.184 ± 0.005) was not significantly different compared to the sedentary normal fed group (N = 0.184 ± 0.010). Resistance training resulted in an elevation in BMD (NT = 0.195 ± 0.011 & DT = 0.192 ± 0.004) compared to the sedentary groups). The results indicate that during the growth period in young female rats, a 20% CR diet did not impact tibia BMD, nor did CR alter the resistance training-induced elevation in BMD.

Pathogenic variants in the SLC34A1 gene, which encodes the sodium-phosphate cotransporter NaPi-IIa, lead to a spectrum of renal tubular disorders, including infantile hypercalcemia type 2, nephrolithiasis/osteoporosis-hypophosphatemia type 2, and Fanconi renotubular syndrome type 2. Despite increasing recognition of SLC34A1-related disorders, data on genotype-phenotype correlations and treatment response remain limited due to the rarity of the condition. We retrospectively analyzed the clinical, biochemical, and molecular features of 11 patients from unrelated families carrying 12 pathogenic or likely pathogenic SLC34A1 variants, three of which were novel. Next-generation sequencing and ACMG-AMP criteria were used for variant classification. Biochemical parameters including serum phosphate, calcium, parathyroid hormone, urinary calcium, and TmP/GFR were evaluated. Treatment response to oral phosphate supplementation was longitudinally assessed. All patients exhibited hypercalciuria and nephrocalcinosis at diagnosis. Oral phosphate supplementation (5-20 mg/kg/day) resulted in normalization of urinary calcium excretion in 10 of 11 cases, regardless of baseline serum phosphate status. Linear growth improved in all but one patient. The identified mutations clustered primarily within functional domains of the NaPi-IIa protein, particularly amino acid residues 109-205 and 375-487. Several splice-site and codon-specific variants-such as those affecting Gly153 and Gly194-were highlighted as potential pathogenic hotspots. Our findings expand the mutational and phenotypic spectrum of SLC34A1-related disease and reinforce the utility of oral phosphate supplementation in managing hypercalciuria and promoting growth. Functional domain mapping and variant clustering analyses enhance understanding of disease mechanisms and support the importance of early diagnosis and long-term surveillance.

Sarcopenia-osteoporosis, the concomitant loss of muscle and bone mass, is a geriatric comorbidity that significantly increases the risk of falls, fractures, and mortality. Despite the acknowledgment of muscle-bone crosstalk, the underlying mechanism driving their simultaneous decline remains poorly understood, resulting in a lack of effective integrated therapies. This review aims to elucidate the "inflammation-energy metabolism axis" as the central driver of this condition. This review contends that sarcopenia-osteoporosis is not a coincidental comorbidity but a single pathological syndrome driven by the failure of the inflammation-energy metabolism axis. Its pathophysiology is a self-sustaining vicious cycle where chronic low-grade inflammation (inflammaging) and dysregulated energy metabolism (notably mitochondrial dysfunction and insulin resistance) reciprocally amplify each other, leading to synchronous muscle and bone deterioration. The review first details how chronic inflammation, via pathways like NF-κB and the NLRP3 inflammasome, promotes muscle catabolism and bone resorption. Second, it explains how an energy crisis, stemming from mitochondrial damage and insulin resistance, impairs anabolic processes in both tissues. Finally, the underlying cycle is revealed: inflammation disrupts metabolic pathways (e.g., PI3K/AKT/mTOR), while metabolic stress releases DAMPs that further fuel inflammation, trapping the muscle-bone unit in a catabolic state. Understanding this central axis necessitates a paradigm shift from single-target treatments to systemic interventions. Future strategies should focus on disrupting this vicious cycle through combination therapies (e.g., anti-inflammatory and pro-metabolic agents), gut microbiota modulation, and exercise, offering novel approaches to this debilitating comorbidity.

While it is well known that hyperthyroidism is associated with decreased bone mineral density, other Dual Energy X-ray Absorptiometry (DXA) derived indices, such as proximal hip geometry and body composition parameters, have not been well studied in India. This study was undertaken to comprehensively assess DXA-derived parameters and bone turnover markers in premenopausal women aged 25-45 years, and to compare these with age- and BMI-matched female controls. This was a case-control study done over a period of one year. Premenopausal women aged 25-45 years with a diagnosis of Graves' disease were recruited from the Endocrinology outpatient department (OPD) and healthy controls from the community by sample-level matching. Evaluation of bone biochemistry and assessment of DXA-derived indices were carried out. Forty-one premenopausal subjects with hyperthyroidism and 73 age- and BMI- matched controls were recruited into the study. The mean BMD at lumbar spine(LS), femoral neck(FN) and trabecular bone score were significantly lower among cases as compared to controls, while bone turnover markers were higher in subjects with hyperthyroidism (p < 0.05). Measures of proximal hip geometry were impaired in Graves' disease as compared to controls, with significant differences being noted in CSA at NN [2.57 ± 0.34 vs 2.83 ± 0.50 cm²; P = 0.015], SM/Z at NN [1.09 ± 0.20 vs 1.22 ± 0.21 cm³; P = 0.008] and CSA at IT [4.56 ± 0.82 vs 5.06 ± 1.11 cm²; P = 0.037]. A significantly greater proportion of cases had sarcopenia when compared to controls (27% versus 1.4%; p < 0.001). In rural premenopausal subjects from southern India with hyperthyroidism, a comprehensive assessment of bone health demonstrated significant differences in proximal hip geometry, trabecular microarchitecture and body composition as compared to healthy controls.

The bioactive compounds in ginger provide multiple potential health benefits, such as antioxidant effects and the ability to regulate metabolites processes. Most of these effects are involved in the mechanisms underlying sarcopenia, but the association between daily ginger consumption and the risk of sarcopenia has not been explored in population-based observational studies. This study aimed to investigate whether daily ginger consumption is associated with the risk of sarcopenia in older adults. This cohort study included 2415 older adults from the TCLSIH Cohort Study. Ginger consumption was assessed using a validated self-administered food frequency questionnaire, and sarcopenia was defined using the AWGS 2019 algorithm for sarcopenia. Multivariable Cox proportional hazards regression models were used to examine the association between daily ginger consumption and the risk of sarcopenia. Over a follow-up period of 9437 person-years, 426 incident cases of sarcopenia were documented, with a median follow-up of 4.0 years. After adjusting for sociodemographic, dietary, and lifestyle variables, the multivariable-adjusted hazard ratios (95% CI) for sarcopenia across increasing quartiles of daily ginger consumption were 1.00 (reference), 0.97 (0.75, 1.26), 0.97 (0.75, 1.24) and 0.66 (0.47, 0.91) (P for trend = 0.04), respectively. There was no significant interaction between daily ginger consumption and sex in association with the risk of sarcopenia (P for interaction = 0.80). Our finding indicated that higher ginger consumption is associated with a reduced risk of sarcopenia among older adults. Further studies are needed to determine the causal association.

Metaphyseal chondrodysplasia type Schmid (MCDS), a rare skeletal disorder caused by COL10A1 mutations, exhibits significant phenotypic heterogeneity, yet genotype-phenotype correlations remain poorly defined. We aim to determine the clinical and radiographic manifestation, mutational features, and genotype-phenotype relationships by characterization of 4 patients with MCDS and literature review. The four patients presented with short stature or waddling gait, flattened vertebrae, and irregular femoral epiphyses. We identified two novel COL10A1 variants (c.1925 T > A, c.1903C > G) and reported the first case harboring both a de novo nonsense (c.2001 T > G, p.Tyr667Ter) in the non-collagenous 1 (NC1) domain and a missense (c.1438A > T, p.Ile480Leu) in the helix domain. Genotype-phenotype analysis of 124 cases previously reported and 4 new cases revealed that NC1 domain mutations were associated with an earlier onset of MCDS than non-NC1 mutations (median 12 vs. 72 months, P = 0.0014). Patients carrying a missense mutation in COL10A1 showed significantly lower height Z-scores (- 3.62 ± 1.95 vs. - 1.99 ± 1.28, P = 0.013) at first and more metaphyseal irregularities in the distal radius/ulna than those with truncating mutations (P = 0.019). Structural modeling indicated that NC1 mutations may disrupt collagen X structure via electrostatic alterations or steric clashes. These findings expand the mutational spectrum of MCDS and establish that COL10A1 genotype correlates with severity of MCDS, which will help to identify patients with severe phenotypes through molecular testing and to develop effective treatment strategies for MCDS.