Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23 (FGF23) secretion. However, TIO lesions located in the neurocranium (NC) and intracranial (IC) structures remain poorly characterized. To characterize the clinical features of TIO lesions in NC and IC structures and to compare them with those located in the sinuses. This retrospective study included patients diagnosed with TIO who underwent tumor resection at Peking Union Medical College Hospital between January 2016 and December 2023. Patients with lesions in NC and IC structures were defined as the study group, while those with sinus lesions served as the control group. Clinical characteristics, biochemical parameters, and surgical outcomes were systematically analyzed and compared between groups. TIO lesions in NC and IC structures were distributed across the skull base, temporal region, sellar region, frontal lobe, and occipital region. Compared with sinus lesions, patients with NC and IC lesions showed comparable clinical and biochemical profiles but exhibited significantly worse outcomes, including higher rates of non-remission and tumor recurrence. These findings suggest increased difficulty in complete tumor resection and disease control in this subgroup. TIO lesions in NC and IC structures are associated with poorer surgical outcomes and higher recurrence rates despite similar baseline characteristics. These results highlight the need for improved localization strategies and tailored management approaches for this challenging subgroup.

ContextFibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder frequently manifesting in childhood, often leading to progressive bone lesions, pain and functional impairment. Denosumab as a monoclonal antibody targeting RANKL has emerged as a potential therapeutic option, while its safety and efficacy in pediatric population remains poorly defined.ObjectiveInvestigate the efficacy and safety of denosumab in pediatric FD/MAS population.Design12-month single-arm study.SettingSingle center study at Peking Union Medical College Hospital.PatientsFD/MAS patients under 18.InterventionsDenosumab 1mg/kg with a maximum dosage of 60mg every 3 months for 12-month follow-up.Main outcome measuresFD-related bone pain, bone turnover markers, 99mTc-MDP bone scintigraphy, bone mineral density.ResultsIn 5 pediatric FD/MAS patients treated with denosumab, significant clinical improvements were observed, including alleviation of FD-associated bone pain, reductions in bone turnover markers, and regression of FD lesions. Alkaline phosphatase levels dropped to an average of 41.8% of baseline, accompanied by concurrent reductions in C-terminal telopeptide and type 1 N-terminal pro-peptide levels. Adverse events particularly hypercalcemia following treatment cessation occurred in 2 of the 5 patients, indicating a relatively high incidence of rebound hypercalcemia and highlighting the need for careful monitoring and cautious use of denosumab in pediatric patients.ConclusionsDenosumab appears to be effective in pediatric FD/MAS patients, however safety concerns remain. Comprehensive pre-treatment evaluation and close monitoring throughout the treatment course are essential. Further prospective studies and randomized controlled trials are needed to determine optimal dosing strategies and establish long-term safety in this population.

This study develops a machine learning model to predict osteoporosis in Chinese postmenopausal women. The model was trained using the largest nationwide cohort and externally validated. It showed AUCs of 0.744–0.798 and demonstrated prognostic value for 5-year fracture risk, supporting population-level screening where DXA resources are limited. Osteoporosis is highly prevalent among Chinese postmenopausal women, yet underdiagnosis remains due to limited DXA availability. We aimed to develop and validate a machine learning–based model for osteoporosis prediction using easily obtainable variables. The model was trained using data from the largest nationwide cohort (China Osteoporosis Prevalence Study, n = 6,574) and externally validated in two independent cohorts: the China Vertebral and Osteoporosis Study (n = 1,758) and the Peking Vertebral Fracture Study baseline (n = 1,439). Five predictors selected via LASSO regression were used to train the prediction model. Model performance was evaluated by area under the curve (AUC) and calibration plot. To evaluate its ability to predict future fractures, the model was evaluated in a 5-year follow-up cohort (n = 795). A web-based calculator was developed for public use. The model showed strong discrimination (AUC: 0.798 in the training cohort; 0.775 in the internal validation cohort; 0.750 and 0.744 in the external validation cohorts) and good calibration across all cohorts. A rule-out threshold (≥ 0.098) demonstrated high sensitivity (94.7

Background Insights into basic bone biology and genetic disorders have led to advances in the treatment of osteoporosis. However, new drugs for the treatment of osteoporosis in men remain insufficient. We investigated the efficacy of a novel anti-Dkk1 monoclonal antibody (Dkk1-mAb) and its sequential alendronate treatment in a mouse model of osteoporosis induced by orchiectomy. Methods A specific Dkk1-mAb was generated using the hybridoma technology. A total of 40 male C57BL/6 mice aged 12 weeks underwent orchidectomy or sham surgery. At 8 weeks postoperatively, the orchiectomized mice were randomly divided into 4 groups (8 in each group) to receive treatment of Dkk1-mAb, alendronate, Dkk1-mAb followed by alendronate, or placebo. After 8 weeks of treatment, the mice were euthanized, and bone mineral density (BMD), skeletal mechanical properties, bone histology, bone turnover biomarkers, serum levels of Dkk1 and sclerostin, muscle properties, and activity of the Wnt signaling were evaluated. Results After 8 weeks of treatment, serum Dkk1 levels were lower in Dkk1-mAb and sequential groups than placebo group (P < 0.001, P < 0.05). L1-5 BMD was higher in Dkk1-mAb, alendronate, and sequential groups by 11.9 %, 22.8 %, and 23.1 % than placebo group (P < 0.05 or P < 0.001), with BMD at left femur increased by 12.8 % and 21.0 % in alendronate and sequential groups than placebo group (P < 0.05 or P < 0.001). The sequential group exhibited higher vertebral trabecular volume/total volume (39.9 %), bone surface/total volume (25.8 %), trabecular BMD (4.0 %), and trabecular thickness (13.1 %) than Dkk1-mAb group (P < 0.01 or P < 0.001), and higher cortical BMD, thickness than Dkk1-mAb (2.9 %, P < 0.01; 6.6 %, P < 0.05) and alendronate (2.2 %, 5.7 %, all P < 0.05) groups. All treatment groups showed greater bone strength, cross-sectional area of muscle, and grip strength than placebo group. The expression of Lef1 was significantly increased in bones of Dkk1-mAb and sequential groups. No pathological abnormalities in vital organs were found in all groups, suggesting that Dkk1-mAb had a good safety profile. Conclusions The novel Dkk1-mAb has therapeutic potential in osteoporosis, which can increase BMD and bone strength, improve bone microarchitecture and muscle performance of orchiectomy-induced osteoporotic mice through activating the WNT pathway, and its sequential treatment with alendronate achieves additive benefits. The Translational Potential of this Article This study found that the novel Dkk1-mAb can increase BMD and bone strength, improve bone microarchitecture and muscle performance of orchiectomy-induced osteoporosis mice, and sequential treatment with Dkk1-mAb and alendronate achieves additive benefits. Dkk1-mAb has translational potential for the treatment of osteoporosis.

Purpose Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder characterized by both skin and skeletal abnormalities and is classified into two subtypes: PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2). Cyclooxygenase-2 (COX-2) inhibitor Etoricoxib is first-line medication for PHO which could alleviate digital clubbing and pachydermia. However, its effects on the skeletal abnormalities associated with PHO remain unclear. This study aims to comprehensively investigate changes in bone microarchitecture at the distal radius, tibia and interphalangeal bones in PHO patients after 12-month Etoricoxib treatment. Methods A total of 20 PHO patients were enrolled, including 9 PHOAR1 patients and 11 PHOAR2 patients. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results After 12 months' treatment, periosteosis in long bones and osteolysis at the 3rd interphalangeal joint of PHO were visually reduced. HR-pQCT parameters revealed improvements in total volumetric bone mineral density (Tot.vBMD), cortical vBMD (Ct.vBMD) at distal radius and tibia, accompanied with decreased cortical porosity. Trabecular bone showed no significant improvement. Besides, bone stiffness and failure load were significantly enhanced at radius site. In subgroup analysis, PHOAR2 patients experienced decline in trabecular number at the distal tibia, a change not observed in PHOAR1 patients. Correlation analysis revealed inverse associations between disease duration and changes in vBMD and bone strength in PHOAR2 patients, whereas no significant associations were found in PHOAR1 patients. Conclusions Our findings indicated that 12 months of Etoricoxib treatment improved bone microstructure in PHO patients and highlighted differential treatment responses between different genotypes, which might optimize treatment strategies for PHO patients.

Introduction Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).Methods and analysis This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.Ethics and dissemination The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.Trial registration number NCT05866029.

Purpose:Neural EGF-like 1 (Nell-1), originally implicated in craniosynostosis, has been identified as a key regulator in osteogenic processes. While preclinical data were encouraging, clinical studies correlating serum Nell-1 levels with osteoporosis remain scarce. This study aims to investigate the relationship between circulation Nell-1 level and bone turnover markers, bone mineral density (BMD), bone microstructure, muscle strength, fall risk, and fractures in Chinese postmenopausal women. Methods:Serum Nell-1 levels were measured in 123 Chinese postmenopausal women. Muscle function was evaluated through grip strength tests, the Short Physical Performance Battery (SPPB), and the Timed Up and Go (TUG) test. Dual-energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD), lumbar trabecular bone score (TBS), and muscle mass. High-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to determine volumetric bone mineral density (vBMD), analyze bone microarchitecture, and estimate bone strength. Result:Postmenopausal women with higher serum Nell-1 levels had higher aBMD and total volumetric bone mineral density (Tot.vBMD) at the distal tibia, larger cortical area (Ct.Ar) and thicker cortical thickness (Ct.Th) at the distal tibia, and higher bone strength. There was a significant negative association between serum Nell-1 levels and C-terminal cross-linking telopeptide of type I collagen (β-CTX), while no significant correlations were observed between serum Nell-1 levels and muscle mass or function. Conclusion:Postmenopausal women with higher serum Nell-1 levels exhibited higher BMD and bone strength, indicating its potential as a therapeutic invention for osteoporosis.

Context: Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic RASopathy characterized by epidermal or melanocytic nevi, skeletal dysplasia, and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets. However, its bone microarchitectural features remain underdefined.Objectives: The study aimed to characterize the clinical, genetic, and skeletal microarchitectural features of CSHS.Methods: We summarized clinical findings of 6 CSHS patients with genetically confirmed somatic RAS mutations. Skeletal involvement was assessed by whole-body bone scintigraphy. High-resolution peripheral quantitative computed tomography parameters at the distal radius and tibia were compared with age- and sex-matched XLH controls (1:3). Literature review of 20 genetically confirmed CSHS patients was performed to assess genotype-phenotype correlation.Results: All patients were confirmed to carry somatic HRAS or NRAS mutation in affected skin. Hypophosphatemia, elevated alkaline phosphatase and FGF23 were found in all patients. Genotype-phenotype correlation analysis did not identify any significant biochemical or systemic burden differences across 3 genotypes. Compared with XLH controls, CSHS patients exhibited significantly reduced total and trabecular volumetric BMD (vBMD), with relatively preserved cortical vBMD. Bone cross-sectional geometry was less expanded than in XLH at the tibia. In addition, thinner trabeculae with greater separation were found at the radius, and the distal tibia showed thinner and decreased cortical porosity. Estimated bone stiffness and failure load were significantly lower at both the radius and tibia.Conclusions: CSHS is associated with pronounced trabecular microarchitectural impairment and reduced bone strength that exceed the expected effects of FGF23-mediated phosphate wasting alone, supporting a combined contribution of intrinsic skeletal dysplasia and chronic hypophosphatemia.

This study estimated FRAX®-based intervention thresholds for initiating osteoporosis treatment in Chinese postmenopausal women, using real-world data from the largest nationally representative osteoporosis survey in China and a validated Markov microsimulation model. Denosumab became cost-effective at a 10-year major osteoporotic fracture probability of 7

PurposeHigh serum periostin is linked to an increased risk of osteoporotic fractures in postmenopausal women. However, the relationships between serum periostin and bone microarchitecture, particularly muscle mass, and muscle function remain unclear. This study aims to investigate the relationships between serum periostin and bone mineral density, bone microarchitecture, muscle mass and function, falls, and fractures in community-dwelling Chinese postmenopausal women.MethodSerum periostin levels were measured in 135 Chinese postmenopausal women. Dual-energy X-ray absorptiometry assessed areal bone mineral density (aBMD), lumbar trabecular bone score (TBS), and muscle mass. High-resolution peripheral quantitative computed tomography (HR-pQCT) evaluated bone microarchitecture. Muscle function and fall risk were assessed using handgrip strength, the Short Physical Performance Battery (SPPB), the Timed Up and Go (TUG) test, and the Falls Risk for Older People in the Community (FROP-Com) screening tool.ResultThe mean serum periostin was 1770.3 ± 440.4 pmol/L. Serum periostin was negatively correlated with bone microarchitecture parameters, total area (Tot.Ar), cortical perimeter (Ct.Pm), trabecular area (Tb.Ar), estimated bone strength stiffness, and failure load. Negative correlations were also found with appendicular skeletal muscle mass (ASM), balance test scores, and gait speed. Conversely, serum periostin was positively correlated with TUG time and FROP-Com scores.ConclusionHigher serum periostin is associated with smaller bone cross-sectional area, lower estimated bone strength, reduced muscle mass, and higher fall risk, indicating its potential as a predictor for assessing skeletal and muscular health in postmenopausal women.

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorders characterized by fibro-osseous skeletal lesions and hyperfunctioning endocrinopathies. Large-scale pediatric cohort data from China remain scarce. We aimed to characterize the phenotypic spectrum of Chinese children with FD/MAS and examine cross-sectional associations between skeletal distribution and endocrine phenotypes. Methods: We conducted a nationally representative retrospective cross-sectional study at Peking Union Medical College Hospital. Patients aged ≤18 years diagnosed with FD/MAS between January 1st 2015 and December 31st 2024, with complete baseline data were included. Main outcomes include demographic features, clinical manifestations, skeletal manifestations, endocrine manifestations, and serum profile. Skeletal involvement was categorized by anatomical region and quantified using the Skeletal Burden Score. Associations between skeletal lesion distribution and endocrinopathies were evaluated using odds ratios. Unsupervised hierarchical clustering assessed symptom patterns at onset. Random forest classification models identified baseline features associated with pituitary adenoma and peripheral precocious puberty in girls. Findings: Of 137 screened pediatric patients, 90 were included (56·7% female). Median age at symptom onset was 5·0 years, with a median diagnostic delay of 2·0 years; 21·1% experienced delays exceeding five years. MAS was present in 76·7% of patients, polyostotic FD in 94·4%, and craniofacial involvement in 76·7%. Among MAS cases, peripheral precocious puberty occurred in 52·2%, hyperthyroidism in 29·0%, pituitary adenoma in 21·7%, and hypophosphatemia in 5·8%. Two phenotype clusters were identified at disease onset. Craniofacial involvement was associated with pituitary adenoma (OR 10·71, 95%CI 2·34-49·08), while pelvic involvement in girls was associated with peripheral precocious puberty (OR 20·94, 95% CI 4·52-96·97). Random forest models yielded AUCs of 0·799 (95%CI 0·625-0·973) for pituitary adenoma and 0·917 (95%CI 0·782-1·000) for peripheral precocious puberty. Interpretation​: This national pediatric cohort demonstrates substantial diagnostic delay, high skeletal, and endocrine burden. Anatomical skeletal distribution is cross-sectionally associated with specific endocrinopathies, supporting anatomy-informed surveillance strategies that warrant prospective validation.

Purpose:To investigate the links between abdominal obesity and skeletal outcomes in a population-based cohort in China. Methods:8,251 participants from the COPS cohort were enrolled in this study and categorized by quartiles of abdominal obesity indices. Abdominal obesity was determined using sex-specific waist circumference (WC) cutoffs (≥ 90 cm for males, ≥ 85 cm for females), or a waist-to-height ratio (WHtR) ≥0.5. Physical performance and balance were assessed using the Five-Repetition Sit-to-Stand Test (5R-STS) and the Sharpened Romberg test. Vertebral fractures were identified by spine X-ray examination, while information on clinical fractures in recent 5y were collected by a self-report questionnaire. Multivariate regression models were employed with covariate adjustments. Predictive capacity of adiposity metrics for fractures was assessed through ROC analysis. Results:Abdominal obesity was linked to lower bone turnover rate and higher BMD. However, it was also significantly associated with impaired balance, evidenced by prolonged 5R-STS times and higher rates of positive Sharpened Romberg tests. The prevalence of vertebral fractures and clinical fractures in recent 5y increased across quartiles of WC, WHtR, and Chinese visceral adiposity index (CVAI) (all p< 0.001). An increment of one standard deviation (SD) in these indices was linked to a 19%-30% greater prevalence of fractures. These findings remained robust after limiting analysis to Genant grade ≥2 vertebral fractures. BMI-stratified analysis revealed that abdominal obesity independently increased the prevalence of vertebral fractures regardless of BMI. Notably, normal-weight individuals with abdominal obesity had a 1.75-fold higher prevalence of vertebral fractures (p = 0.022), while BMI alone showed no significant effect. Moreover, WHtR demonstrated superior predictive capacity for vertebral fractures and Genant grade ≥2 vertebral fractures vs BMI (AUC 0.62 vs 0.52), with optimal performance when combined with age, sex, fracture history, and BMD (AUC = 0.80). Conclusion:Abdominal obesity was independently associated with impaired balance and elevated prevalence of vertebral fractures and clinical fractures, even in normal-weight individuals. WHtR demonstrated superior discriminative power for vertebral fractures.

Background Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific adipose tissue depots have differential associations with BMD and to assess causality using Mendelian randomization (MR). Methods We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data to evaluate associations between regional fat depots (gynoid, android, visceral, abdominal subcutaneous fat, and total fat percentage) and BMD at total body, femoral neck, and lumbar spine. Multivariable linear regression was used to evaluate these relationships. To assess potential causal effects, we performed two-sample MR using genome-wide association study summary statistics for fat distribution traits and BMD. Results Gynoid fat was positively associated with BMD at the total body, femoral neck, and lumbar spine, while visceral and total body fat showed consistent inverse associations across these regions. Two-sample MR analysis supported a causal effect of gynoid fat on BMD but found no evidence of causality for visceral or total body fat. Conclusions Gynoid fat shows a beneficial and causal effect on BMD, whereas the inverse associations observed for visceral and total body fat appear to be non-causal. These findings underscore the importance of considering fat distribution, not merely total body fat or weight, when evaluating bone health.

Context: X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Previous studies have found deteriorated bone microarchitecture in adults with XLH. Detailed studies on the skeletal microarchitecture of adolescent and pediatric patients with XLH are still lacking. Objective: This study aimed to evaluate bone geometry, density, microarchitecture, stiffness in adolescent and pediatric patients with XLH by using high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: This study utilized HR-pQCT to assess bone geometry, density, microarchitecture, and stiffness in 106 Chinese adolescent and pediatric patients with XLH. Result: Compared with sex- and age-matched controls, patients with XLH had significantly higher trabecular area (Tb.Ar), lower total volumetric bone mineral density, lower cortical volumetric BMD (Ct.vBMD), and lower stiffness at both the distal radius and the tibia after adjusting for height and weight. Alkaline phosphatase Z score (ALP-Z), a marker to reflect the disease activity of rickets, was negatively correlated with Ct.vBMD and cortical thickness at the distal radius, and Ct.vBMD at the distal tibia, and positively correlated with cortical porosity at the distal tibia. We developed an online calculator to estimate Tb.Ar, Ct.vBMD, and stiffness of the distal tibia of adolescent and pediatric patients with XLH based on clinical general characteristic and biochemical indicators. Conclusion: The bone microarchitecture of adolescent and pediatric patients with XLH had deteriorated, and ALP-Z was negatively correlated with the skeletal quality of adolescent and pediatric patients with XLH, especially in the cortical bone. HR-pQCT parameters can be estimated using clinical characteristics and biochemical indicators, which may assist physicians to monitor the disease progression in areas without HR-pQCT access.

CONTEXT:Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder characterized by skeletal and skin abnormalities. Genetic defects in prostaglandin E2 (PGE2) metabolism are known to cause PHO. However, the global impact and clinical significance of eicosanoids and oxylipins beyond PGE2 remain to be elucidated. OBJECTIVE:This study aimed to investigate oxylipin networks in PHO, including the 2 subtypes, PHOAR1 and PHOAR2, and examine their associations with clinical characteristics. METHODS:We conducted a targeted metabolomic study involving 16 patients with PHO and 16 age- and sex-matched healthy controls. Serum samples were collected at the time of diagnosis. Metabolites were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. RESULTS:Laboratory analyses confirmed elevated levels of PGE2 in patients with PHO, consistent with the established pathogenesis. About 60 oxidized lipid metabolites were identified, with 19 differentially expressed in PHO. Besides the COX/PGE2 pathway, the lipoxygenase-mediated pathway was also involved in PHO. The metabolites 5-OxoETE, 15-OxoETE, 8S,15S-DiHETE, PGE2, 11β-PGE2, PGB2, LTB4, and LTE4 were significantly altered. Correlation analyses revealed associations between oxylipin metabolites and clinical features, including bone microarchitecture. Notably, the study highlighted differences in the oxylipin metabolite profiles between patients with PHOAR1 and patients with PHOAR2, suggesting distinct metabolic signatures for each subtype. CONCLUSION:Our study indicated a significant perturbation in oxylipin metabolism among patients with PHO, with distinct metabolic signatures observed between PHOAR1 and PHOAR2. The disruption extended beyond the metabolism of PGE2. It encompassed a broader alteration across the polyunsaturated fatty acid metabolism spectrum, including various eicosanoids and oxylipins. Our work provided a comprehensive understanding of the pathogenesis of PHO, and underscored the potential for subtype-specific therapeutic interventions.

This study presents a preoperative prediction model for tumor-induced osteomalacia (TIO) surgery outcomes on the basis of patient characteristics. The model, which was validated in 309 patients, identifies key risk factors and aids in clinical decision-making to optimize treatment strategies, reduce the number of unnecessary surgeries, and improve patient care. Tumor-induced osteomalacia (TIO) should be curable by complete removal of the causative tumor. Knowledge of the prognosis of surgery is lacking. This study aimed to establish a prediction model that uses the preoperative characteristics of patients to predict the surgical treatment outcomes of patients with TIO. This was a single-center, retrospective, case-control study. The main outcome was the surgical outcomes of patients with TIO. Patients with TIO who underwent surgical treatment were divided into a training set and a validation set. A nomogram was established in the training set, and the model was evaluated by the C-index, calibration curve, and clinical impact curve and verified in the validation set. A total of 309 patients with TIO were included, with 222 in the training set and 87 in the validation set. The C-index of the nomogram was 0.864 (p < 0.001). The model had high goodness of fit—which is suggested by the calibration curve, and clinical benefit is indicated by the decision curve analysis and clinical impact curve. In the validation set, the area under the curve of the prediction model was 0.782 (p < 0.001), and decision curve analysis and clinical impact curve also suggested the existence of clinical benefit. This study established a prognostic model for the preoperative prediction of surgical outcomes for TIO. This model can be used as a reference in clinical practice for the development of individualized treatment strategies.

CONTEXT:Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated. OBJECTIVES:This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis. METHODS:20 TIO patients, 20 individuals with normal glucose tolerance, and 20 patients with type 2 diabetes mellitus (DM) were enrolled and underwent an oral glucose tolerance test (OGTT). Serum phosphate and FGF23 concentration were monitored during OGTT. RESULTS:In patients with TIO, 60% (12/20) exhibited impaired glucose tolerance (IGT) and 5% (1/20) had type 2 DM. Those with IGT or type 2 DM experienced more ambulatory difficulties (69.2% vs 42.9%), lower phosphate concentrations (0.43 ± 0.10 vs 0.53 ± 0.10, P = .042), and lower calcium concentrations (2.20 ± 0.08 vs 2.30 ± 0.40, P = .001) compared to TIO patients without these conditions. According to correlation analysis, serum phosphate levels were negatively correlated with plasma glucose levels at 60 minutes (P < .001), fasting plasma insulin levels (P < .05), and homeostasis model assessment for insulin resistance (P < .05). Those with high FGF23 levels had a higher glucose level at 60 minutes (10.5 [9.3, 12.3] vs 7.3 [6.4, 10.1], P = .048) than that of low group. After glucose loading, both FGF23 and phosphate levels exhibited a decreasing trend. CONCLUSION:The development of diabetes in TIO patients may be predisposed by ambulatory issues, low phosphate, and elevated FGF23 levels. Dysglycemia might further aggravate hypophosphatemia.

BACKGROUND AND AIMS:Vitamin D deficiency is a global public health concern, yet data on its prevalence across China's diverse demographics remain limited. This study aimed to evaluate vitamin D status and deficiency prevalence across various demographic and geographic groups in China. METHODS AND RESULTS:This cross-sectional analysis included 19,845 participants from the China Osteoporosis Prevalence Study, conducted between December 2017 and August 2018. Serum 25-hydroxyvitamin D (25OHD) was measured by electrochemiluminescence. Vitamin D levels and deficiency prevalence were assessed across demographic groups and provinces using weighted analysis. The mean 25OHD level in the general population was 26.00 ng/mL, with an average of 29.1 ng/mL in males and 22.84 ng/mL in females. Vitamin D deficiency (defined as 25OHD <20 ng/mL) was notably prevalent in China, affecting 29.89 % of the population. Deficiency rates were particularly high in northern China (44.02 %), females (39.95 %), individuals under 40 years old (33.46 %), individuals with obesity (32.54 %), and urban residents (39.44 %). Geographic disparities were also apparent at the provincial level, with southern provinces generally exhibiting lower prevalence and northwestern regions the highest. CONCLUSIONS:This study provides important evidence for public health policies to prevent and manage vitamin D deficiency, highlighting the need for targeted interventions among high-risk populations such as women, urban residents, individuals with high BMI, and those with conditions like diabetes.

Context Osteopetrosis (OPT) is a rare skeletal disease characterized by high bone mass that has 2 major inheritance patterns: autosomal dominant osteopetrosis and autosomal recessive osteopetrosis (ARO). However, comprehensive descriptions of bone microarchitecture in OPT patients are limited.Objectives The aim of this study was to comprehensively investigate the bone microarchitecture of OPT patients, explore age-related bone alterations, and describe the skeletal heterogeneity among different genotypes.Methods Nine OPT patients, including 7 with autosomal dominant osteopetrosis and CLCN7 mutations, 1 ARO patient with CAII mutation, and 1 ARO patient with TCIRG1 mutation, were retrospectively enrolled in this study. Clinical and biochemical examinations were performed. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography.Results Compared with age- and sex-matched healthy controls, OPT patients had greater total volumetric bone mineral density. In addition, trabecular bone was denser, with greater trabecular volumetric bone mineral density, increased trabecular number, and decreased trabecular separation. However, the cortical bone in OPT patients was weaker, characterized by increased cortical thickness and porosity. OPT patients exhibited characteristic patterns, including bone islets and uneven dense structures, on the representative reconstruction high-resolution peripheral quantitative computed tomography images. Skeletal heterogeneity across different genotypes was observed, with looser cortical bone in 1 OPT patient with CAII mutation and thicker cortical bone in 1 OPT patient with TCIRG1 mutation.Conclusion Compared with healthy controls, OPT patients presented with denser trabecular bone, thicker but looser cortical bone, unique bone patterns, and skeletal heterogeneity. These results provide new insights into bone alterations in OPT patients.

Although obesity is generally associated with increased bone mass, recent data have challenged its potential protective effect. Our study found that increased BMI showed beneficial effects on BMD in a non-linear way. However, individuals with obesity, especially women, were more likely to have vertebral fractures. There was a U-shaped relationship between BMI and the prevalent fractures. To estimate the association of obesity with the prevalence of fractures in the Mainland Chinese population. A total of 8251 individuals from the COPS cohort were enrolled in this cross-sectional study and grouped by BMI level. The Five-Repetition Sit-to-Stand Test (5R-STS) and the Sharpened Romberg test were used to evaluate the balance ability. Vertebral fractures (VFs) were confirmed by spine X-ray examination. Prevalent fractures were defined by a self-report questionnaire which happened in the recent 5 years. The restricted cubic spline (RCS) was used to explore the non-linear relationship. Multiple linear regression and multivariable logistic regression were conducted to adjust the covariates. Obesity was correlated with a reduced bone turnover rate and increased BMD. Nevertheless, there were significant non-linear correlations between BMI and BMD, with a rapid increase and plateau at extremely high BMI levels (p for non-linear < 0.001 for all). Individuals with obesity were associated with a longer time of the 5R-STS and more likely to have a positive Sharpened Romberg test, especially in women. Compared with the normal weight group, the likelihood of prevalence of VFs and the prevalent fractures were significantly increased in the obesity group, independent of the Sharpened Romberg test and lumbar spine BMD (VFs: OR = 1.88 [95