Objective: Undercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population.Methods: This is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1–4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured.Results: We found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; p < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40–49 years in both men [2.55 ng/ml (95% CI = 1.96–3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12–2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = −0.128, p = 0.013; women, r = −0.321, p < 0.001), femoral neck (men, r = −0.095, p = 0.062; women, r = −0.260, p < 0.001), and total hip (men, r = −0.123, p = 0.015; women, r = −0.209, p < 0.001) and higher P1NP (men, r = 0.307, p < 0.001; women, r = 0.239, p < 0.001) and β-CTX (men, r = 0.169, p = 0.001; women, r = 0.354, p < 0.001) levels in both men and women. Furthermore, we also showed that a 1 − SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and women, respectively (men, 95% CI = 1.25–2.13, p = 0.004; women, 95% CI = 1.19–2.42, p = 0.004).Conclusions: We first revealed the profile of serum ucOC levels according to gender and age in the Chinese population and demonstrated the associations of ucOC with BMD and BTMs and the risk of prevalent osteopenia or osteoporosis. Our findings provide a clue to elucidate the function of ucOC in bone metabolism.

Background: Vitamin D is a key factor in bone metabolism, yet vitamin D insufficiency and deficiency are prevalent among postmenopausal women, with potential repercussions on bone mineral density (BMD), bone turnover markers (BTMs), and parathyroid hormone (PTH). Nonetheless, the findings from existing studies exhibit inconsistency, and a notable gap exists in the availability of large-scale investigations.Methods: In this real-world study, 8,532 postmenopausal women over 50 years old with a diagnosis of osteopenia (50.9%) and osteoporosis (49.1%) at the first visit were enrolled in this study. Serum 25(OH)D level, PTH, osteocalcin (OC) and Beta-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured. BMD at all sites, including the lumbar spine, femoral neck, and total hip were obtained by dual-energy X-ray absorptiometry (DXA). The associations of serum 25(OH)D level with BMDs and BTMs were investigated using spearman correlation analysis and analysis of general linear model adjusted by age and body mass index.Results: The serum 25(OH)D level was 22.17 ± 9.75 ng/mL among all patients included in this study. For the osteopenia group, the serum 25(OH)D level was 22.40 ± 9.41 ng/mL, while for the osteoporosis group, it measured 21.93 ± 10.08 ng/mL. In the osteopenia group, the prevalence of vitamin D deficiency, insufficiency and sufficiency was 45.8, 34.6, and 19.6%, respectively, which was close to that of the osteoporosis group (47.4, 34.3, and 18.3%) (p = 0.202). Spearman correlation analysis unveiled negative associations between serum 25(OH)D concentrations and both BTMs and PTH within both the osteopenia and osteoporosis group. In the osteoporosis group, there were positive correlations between 25(OH)D levels and femoral neck BMD (r = 0.040, p = 0.010) and total hip BMD (r = 0.053, p = 0.001). Furthermore, we found that for the osteopenia group, greater vitamin D levels were associated with greater femoral neck BMD (p = 0.020) and total hip BMD (p = 0.008) and lower β-CTX (p < 0.001), OC (p < 0.001), and PTH (p < 0.001). The same trends were seen in osteoporosis patients (p < 0.05), and with greater lumbar spine BMD with higher levels of 25(OH)D (p = 0.009).Conclusion: This study showed high prevalence of vitamin D deficiency and insufficiency in Chinese postmenopausal women with osteopenia and osteoporosis and the relationships between vitamin D and BMD, BTMs and PTH. The results contribute to a more comprehensive understanding of how vitamin D may impact bone health.

Hypophosphatasia (HPP) is an inherited disease caused by ALPL mutation, resulting in decreased alkaline phosphatase (ALP) activity and damage to bone and tooth mineralization. The clinical symptoms of adult HPP are variable, making diagnosis challenging. This study aims to clarify the clinical and genetic characteristics of HPP in Chinese adults. There were 19 patients, including 1 with childhood-onset and 18 with adult-onset HPP. The median age was 62 (32–74) years and 16 female patients were involved. Common symptoms included musculoskeletal symptoms (12/19), dental problems (8/19), fractures (7/19), and fatigue (6/19). Nine patients (47.4%) were misdiagnosed with osteoporosis and six received anti-resorptive treatment. The average serum ALP level was 29.1 (14–53) U/L and 94.7% (18/19) of patients had ALP levels below 40 U/L. Genetic analysis found 14 ALPL mutations, including three novel mutations—c.511C>G (p.His171Ala), c.782C>A (p.Pro261Gln), and 1399A>G (p.Met467Val). The symptoms of two patients with compound heterozygous mutations were more severe than those with heterozygous mutations. Our study summarized the clinical characteristics of adult HPP patients in the Chinese population, expanded the spectrum of pathogenic mutations, and deepened clinicians’ understanding of this neglected disease.

Introduction: This study aimed to investigate the relationship of gene polymorphisms and fat mass (FM) in Chinese population. Material and methods: Healthy males, premenopausal and postmenopausal women were recruited. Single Nucleotide Polymorphisms (SNPs) and FM were measured. Results:...

Objective: CLCN7 mutation caused abnormal osteoclasts, resulting in osteopetrosis. Depending on the type of mutation, CLCN7 mutations can lead to severe or relatively benign forms of osteopetrosis. However, the serum metabolic alterations in osteopetrosis caused by CLCN7 mutation are still unknown. We aimed to investigate the differences in the metabolome of osteopetrosis patients caused by CLCN7 mutation versus healthy controls (HC), uncovering potential subtype diagnosis biomarkers.Methods: 19 osteopetrosis patients caused by CLCN7 mutation and 19 HC were recruited for liquid chromatography–tandem mass spectrometry analysis. The screened pathway was validated in the myeloid cell specific Clcn7^G763R mutant mouse model by quantitative real-time PCR analysis.Results: Three metabolic pathways were significantly enriched, including glycerophospholipid metabolism (P=0.036948), arachidonic acid metabolism (P=0.0058585) and linoleic acid metabolism (P=0.032035). Ten differential expressed metabolites were located in these three pathways and classified ability with areas under the curve over 0.7 in receiver operating characteristic analysis, suggesting a certain accuracy for being the potential biological markers. Especially, we found that the proteins in glycerophospholipid metabolism were predicted to interact with ClC-7 and further verified that the expression of coding genes were significantly up-regulated in myeloid cell specific Clcn7^G763R mutant mouse.Conclusion: This study provides data on serum metabolomics in osteopetrosis caused by CLCN7 mutation and provides new potential metabolic markers and pathways for diagnosis and pathogenesis of osteopetrosis.