Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics. Inguinal hernia containing ovaries, fallopian tubes and uterus occurs rarely in adult females and its association with MRKH syndrome is even more rare and probably unreported. Case presentation: A 43-year-old female who had already undergone a vaginoplasty 20 years ago presented to our clinic with left groin swelling and pain for 3 weeks. Physical examinations revealed a 3-cm palpable mass in the left inguinal region that was difficult to reduce into the abdominal cavity. The diagnosis of MRKH syndrome was considered along with inguinal hernia according to the intraoperative findings within the hernia sac. Although most of the MRKH patients with inguinal hernia underwent open surgery, totally extraperitoneal repair (TEP) operation and mesh placement was performed on this patient and the resected specimen proved to be rudimentary uterus and left oviduct. The patient was discharged 2 days after surgery and free of any complications at 6 months of follow-up. Conclusion: MRKH syndrome may remain undiagnosed until incidentally discovered during surgery for unrelated conditions. TEP approach offers excellent visualization, avoids intraperitoneal adhesions, safe resection of Mullerian remnants and preserves peritoneal integrity for future fertility options.

[This corrects the article DOI: 10.3389/fnut.2026.1782217.].

This study systematically analyzed 72 adults with genetically confirmed hypophosphatasia and compared them with 36 individuals with persistent hypophosphatasemia but negative ALPL variants. Using four routinely available indicators, a simplified diagnostic tool was developed and externally validated to facilitate the early identification of adult hypophosphatasia in clinical practice. Hypophosphatasia (HPP), an underdiagnosed inborn error of disorder caused by ALPL mutations, poses diagnostic challenges in adults due to phenotypic heterogeneity. This study aimed to establish a large adult HPP cohort in China and develop a practical diagnostic tool using routine clinical parameters. Clinical and genetic characteristics were systematically analyzed in 72 genetically confirmed adult HPP patients and 36 individuals with persistent hypophosphatasemia and negative ALPL genetic testing. Two models were developed to predict HPP: Model 0 (alkaline phosphatase (ALP)+pyridoxal-5′-phosphate (PLP)) and Model 1 (ALP+height Z-score+family history+chronic musculoskeletal pain). Model performance was evaluated by tenfold cross-validation, decision curve analysis (DCA) and external validation (n = 40, including 28 HPP). HPP patients exhibited lower ALP (27.0 (21.8, 33.3) U/L vs. 36.00 (32.0, 38.0) U/L; P < 0.001), elevated PLP (214.3 (121.3, 457.7) nmol/L vs. 42.6 (31.9, 63.5) nmol/L; P < 0.001), growth impairment, and higher prevalence of chronic musculoskeletal pain and family history. Optimal ALP and PLP cutoffs were 28.2 U/L and 114.9 nmol/L, respectively. Compound heterozygotes and crown domain variants in ALPL gene showed lower ALP and higher PLP levels. Model 1 performed comparably to Model 0 (AUC 0.918 vs. 0.896; P = 0.513), remained robust in the age-stratified sensitivity analysis (<50 years), and achieved an AUC of 0.833 in external validation. A nomogram based on Model 1 was constructed. This study provides the largest clinical-genetic characterization of adult HPP in China and proposes a simple four-variable nomogram that enables accurate recognition of HPP without PLP testing, facilitating earlier diagnosis in routine practice.

Objective To estimate the effect of denosumab compared with bisphosphonates on reducing the risk of knee or hip osteoarthritis (OA) among adults with osteoporosis in a real-world cohort. Method This new-user, active-comparator retrospective real-world cohort utilized electronic health records from the TriNetX Network. Participants diagnosed with osteoporosis between January 1, 2014 and December 31, 2023 were selected. We used propensity-score matching (PSM) to balance potential confounders between denosumab users and bisphosphonate users. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident knee and hip OA by comparing PSM groups. Results 59,157 new users of denosumab were matched on propensity score to 59,157 participants of bisphosphonate users (mean age 70 years; 87% female). The 10-year incidence probability of knee and hip OA in denosumab users was 19.2% (4,839 events and 14.5% (3,396 events), while in bisphosphonate users it was 21.4% (5,389 events) and 14.4% (3,388 events). Compared with bisphosphonate, denosumab users were significantly associated with a reduced risk of any OA (HR 0.96, 95% CI 0.94-0.98), knee OA (HR, 0.87, 95% CI, 0.84-0.91), but not with hip OA (HR, 0.98, 95% CI, 0.94-1.03), or thumb carpometacarpal OA (HR 0.94, 95% CI 0.87-1.01). These associations were more pronounced among older participants (≥ 65 years, HR 0.88, 95% CI 0.84-0.91 for knee OA), females (HR 0.87, 95% CI 0.83-0.91 for knee OA), and individuals of Asian ethnicity (HR 0.73, 95% CI 0.63-0.84 for knee OA). Conclusions Denosumab use was associated with a reduced risk of incident knee OA compared with bisphosphonates in adults with osteoporosis, with the association being more pronounced among older adults, females, and individuals of Asian ethnicity. This study suggests that denosumab could attenuate the development of knee OA, warranting further clinical trials.

BACKGROUND:Physical activity (PA) is crucial for maintaining bone mass. However, it remains unclear whether the "weekend warrior" (WW) pattern, namely condensing moderate-to-vigorous physical activity (MVPA) into 1 or 2 days per week, is beneficial for bone health. This study aimed to assess the association between the WW pattern and risk of low bone mass and related fractures. METHODS:We conducted a population-based study based on two nationwide databases, including 6972 participants aged 20-59 from the National Health and Nutrition Examination Survey (NHANES), 2007-2010 & 2013-2014 cycles, in which PA was self-reported via the Global Physical Activity Questionnaire; and 52,989 participants aged 37-60 years from UK Biobank (UKB), in which PA was measured by wrist-worn accelerometers over 7 days (2013-2015). In both surveys, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA). Associations were analyzed using survey-weighted linear regression (in NHANES), multivariable linear regression (in UKB), and Cox proportional hazards models for incident fracture (in UKB). RESULTS:In NHANES, both the WW pattern and the regular active (RA) pattern were associated with higher femoral neck BMD compared with the inactive group (WW: β = 0.021, 95% CI 0.008-0.035, P = 0.004; RA: β = 0.015, 95% CI 0.007-0.023, P = 0.001), and both were associated with significantly lower odds of low bone mass. In UKB, similar favorable BMD associations were observed, and the WW pattern was associated with a lower hazard of incident fracture compared with both the inactive group (HR = 0.899, 95% CI 0.824-0.981, P = 0.017) and the RA group (HR = 0.897, 95% CI 0.823-0.976, P = 0.012). CONCLUSIONS:Meeting weekly PA guidelines is associated with favorable bone health indicators and lower fracture risk, regardless of whether activity is concentrated on weekends or distributed throughout the week. The WW pattern may serve as a time-efficient alternative for bone health maintenance.

Objective:Reference intervals (RIs) for vitamin B6 biomarkers remain underexplored in Chinese adults. We aimed to establish age- and sex-specific RIs of pyridoxal 5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), and their ratios (PLP/PL, PLP/PA, and PAr), and to identify independent determinants of these markers. Methods:Vitamin B6 metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The distribution changes were illustrated by sex-stratified age percentile curves (P10/P50/P90). Robust 95% RIs (P2.5-P97.5) were obtained by sex and age (<50 vs. ≥50 years) using the Horn-Pesce method. Sex-stratified multivariable linear regression was conducted to identify the independent determinants of vitamin B6 biomarkers. Results:This study included a community-based sample of 367 healthy adults (197 males and 170 females) with a median age of 49.0 years (range 20.0-80.0 years). Females had higher PLP, PL and PLP/PA, and lower PAr than males (all p < 0.01). In males, percentile curves and age-group contrasts showed age-associated declines in PLP, PLP/PL and PLP/PA and an increase in PAr (all p < 0.05); corresponding indices in females were largely stable. The RIs of PLP (nmol/L) were 10.36-145.87 (males <50 years, n = 103), 13.03-103.46 (females <50 years, n = 87), 9.27-142.96 (males ≥50 years, n = 94), and 16.83-173.06 (females ≥50 years, n = 83), respectively. Higher ALP levels were associated with lower PLP, PLP/PL and PLP/PA, and higher PAr; albumin was positively related to PLP/PL and PLP/PA, and negatively to PAr; eGFR was positively correlated with PLP/PA, and negatively with PAr. Notably, serum phosphorus was positively associated with PLP, PLP/PL and PLP/PA, and negatively with PAr. Conclusion:We established population-specific, age- and sex-stratified RIs for vitamin B6 biomarkers in healthy Chinese adults, providing a baseline for clinical and laboratory assessment of vitamin B6 metabolism. We also found that ALP, albumin, renal function, and serum phosphorus were closely related to the vitamin B6 status in both males and females.

To explore the correlation between scoliosis and mandibular deviation by analyzing the degree and direction of coronal trunk imbalance and maxillofacial deviation in patients with idiopathic and congenital scoliosis. A total of 68 patients(scoliosis group), among whom 33 adolescents were diagnosed with idiopathic scoliosis(IS group) and 35 congenital scoliosis(CS group),and 21 orthopedically healthy adolescents volunteers served as control group were involved in this survey. All the patients and volunteers were undertaken the coronal full-length X-ray radiographs of spine and craniofacial CBCT. Landmarks and lines were recorded to measure these films. ANOVA LSD test was applied to evaluate the difference between mandibular deviation and trunk balance among three groups. The relationship of spine coronal morphology, trunk balance and mandibular deviation was evaluated with the Pearson correlation method. The degree of mandibular deviation in both IS and CS groups were significantly higher than that in control group (P<0.05). And significant difference could be found among the three groups in all the five parameters of trunk imbalance. The oblique angle of cervical spine were 5.25±3.94°and 5.99±4.65°in ISG and CSG respectively, which were significantly higher (P=0.001**, 0.000**)than control group(1.68±1.23°). No difference was found between ISG and CSG. The angle of shoulder imbalance were 1.75±1.74°and 2.31±1.88°in ISG and CSG respectively，but statistic difference could be found only in CSG. The Cobb angle were 7.80±4.39°, 44.07±13.69°and 76.89±21.51°in control group, ISG and CSG. Both ISG (13.83±18.86mm) and CGS（14.24±15.22mm） group was significantly higher in degree of trunk shift compared with control group (2.29±2.05mm). And both ISG (2.05±2.49°) and CGS（2.90±2.39°） group was significantly higher in angle of pelvis imbalance compared with control group (0.77±0.64°). In both IS and control group, no significant correlation was found between spine coronal morphology, trunk balance and mandibular deviation (P>0.05). In CS group and IS group, angle of shoulder imbalance (P=0.022* and P=0.010*) were significantly correlated with mandibular deviation, and presented a negative linear trend. And the degree of mandibular deviation had a negative correlation with oblique angle of cervical spine，but no linear correlation was found (p=0.06). Patients with scoliosis have varying degrees of mandibular deviation and body posture imbalance. The direction of mandibular deviation was opposite to the direction of oblique cervical spine and the same to the higher side of imbalanced shoulder. There is a correlation between mandibular development and the abnormal posture of the neck and shoulder, suggesting that multidisciplinary early detection, evaluation and treatment for scoliotic patients or high risk population is necessary.

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder primarily characterized by bone fragility. Hearing loss is an extra-skeletal manifestation of OI. This study aims to characterize the audiological findings of a sample of patients with OI in China. A total of 76 patients (aged 4–77 years) were recruited and evaluated using audiometric evaluations, including pure tone audiometry (PTA), acoustic admittance measurements, and distortion-product otoacoustic emissions (DPOAEs). Patients were categorized into 2 age groups: adults (more than 18 years) and children (under 18 years), and classified by hearing type: normal hearing, conductive, sensorineural, or mixed hearing loss. Tympanometry (152 ears) showed 71.7

Purpose:Optimal dosing of denosumab in osteogenesis imperfecta (OI) remains undefined. This prospective cohort study evaluated the 12-month efficacy and safety of denosumab in OI patients, with a historical control study with alendronate. Materials and methods:Eight pediatric patients (1 mg/kg every 3 months; ≤60 mg/dose) and ten adults (60 mg every 6 months) received denosumab. Outcomes included lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone turnover markers (BTMs), vertebral compression fractures (assessed via AI-assisted Genant grading [AI_OVF_SH system]), fracture incidence, height velocity and adverse events. Historical controls (n=25 alendronate-treated OI patients) were analyzed for comparative efficacy. Sensitivity analyses excluded female pediatric participants (n=4) and peri-/post-menopausal adults (n=4) to assess hormonal confounding. Results:Pediatric denosumab recipients exhibited significant LS-BMD (+30.3%, P<0.001) and FN-BMD gains (+38.7%, P=0.001) versus baseline, whereas adults showed non-significant increases (LS: +2.6%, P=0.100; FN: +4.4%, P=0.051). Sensitivity analyses revealed attenuated BTMs suppression in adults after excluding peri-/post-menopausal women (only ALP decreased by 27.9%, P=0.028). Rebound hypercalcemia occurred in 62.5% (5/8) of children, peaking at 2.93 mmol/L. Compared to alendronate, denosumab demonstrated comparable BMD improvements and fracture reduction (P>0.050) but superior pediatric height gain (+5.8% vs. +2.5%, P=0.004). Vertebral area loss decreased significantly with denosumab (-14.6%, P=0.029), unlike alendronate (-8.8%, P=0.296). Adverse events were more frequent with denosumab in children (hypercalcemia: 62.5% vs. 0%, P=0.002). Conclusion:Denosumab demonstrates non-inferior efficacy to alendronate for BMD improvement in OI, with heightened vertebral remodeling and pediatric height gains. However, its overshoot phenomenon in children (rebound hypercalcemia) and hormone-dependent efficacy in adults necessitate risk-stratified use. Age and menopausal status considerations are critical for optimizing denosumab therapy in OI. Clinical trial registration:https://www.chictr.org.cn/bin/project/edit?pid=184231, identifier ChiCTR2300074207.

The 24-hour urinary calcium excretion (UCaE) not only serves as an important indicator of calcium metabolism balance but also correlates with metabolic diseases. However, the distribution of 24-hour UCaE and its relationship with bone metabolism are unknown. To investigate the distribution of 24-hour UCaE and its association with bone metabolism. In this multicenter cross-sectional study, 1239 participants underwent physical examinations at 9 tertiary hospitals. Multivariate linear regression was used to explore bone metabolism associated with 24-hour UCaE. The relationship of bone metabolism with 24-hour urinary calcium excretion/urinary creatinine (UCaE/Ucr) was analyzed by using restrictive cubic splines fitting multiple linear regression model. The 24-hour UCaE median range was 2.27 mmol overall, 2.24 mmol in men, and 2.28 mmol in women. For men, the highest 24-hour UCaE/Ucr was observed in those aged between 30 and 44 years (median: 0.70), whereas the lowest was found aged between 18 and 29 years (median: 0.46). For women, the 24-hour UCaE/Ucr showed a gradual increase with advancing age. In the adjusted model, 24-hour UCaE/Ucr was independently positively associated with 25(OH)D in both men (P = .032) and women (P < .001). It was independently associated with parathyroid hormone (PTH) (P = .031), type Ⅰ collagen-containing cross-linked C-telopeptide (β-CTX) (P = .021) and procollagen type I N-propeptide (P1NP) (P = .048) in men, but not in women. The prevalence of hypercalciuria was 11.6% (men 7.5%; women 14.0%) and significantly varied across age groups and regions (P < .05). This study established reference intervals for 24-hour UCaE in the Chinese population. This study found gender differences in the relationship between 24-hour UCaE and bone metabolism.

Background: Osteoarthritis (OA) is a degenerative joint disease with articular cartilage destruction, triggering a pro-inflammatory response. The aim of this study was to screen key genes associated with fibroblasts based on single-cell transcriptomic data and explore their potential value in OA diagnosis. Methods: We obtained RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data of OA from the Gene Expression Omnibus (GEO) database. The CellChat package for cell-to-cell communication analysis and identification of possible ligand-receptor pairs. High-dimensional weighted gene coexpression network analysis (hdWGCNA) was applied to identify the gene modules, and the key genes in the modules were identified and subjected to functional enrichment analysis. Subsequently, limma packages were used to screen for differentially expressed genes (DEGs) between OA and its control samples. Finally, the R package multipleROC was used to test the diagnostic potential of the screened key genes and to construct an OA diagnostic model using the rms package. Result: Eight cell populations were identified and annotated based on scRNA-seq and the percentage of fibroblasts was the highest. The cell-cell communication analysis has suggested that the highest communication probability was seen between mesenchymal cells/T cells and fibroblasts through the pairs of CD99-CD99. The hdWGCNA analysis suggested that genes of modules M3, M4, M5, M6, and M8 (50 genes in total) were highly expressed in fibroblasts. Thereafter, we obtained 394 DEGs in OA and its control samples and took intersections with 50 modular genes and identified seven central genes (including apolipoprotein D [APOD], biglycan [BGN], MXRA5, THY1, C1QTNF3, dermatopontin [DPT], and osteoglycin [OGN]). The constructed diagnostic models showed good predictive performance with all area under the curve (AUC) values >0.8. Finally, a satisfactory diagnostic model was established using these seven genes, and the differences in mRNA expression levels of these genes in OA and normal tissues were verified. Conclusion: For the first time, our study systematically screened and validated key genes with diagnostic potential based on fibroblast-specific single-cell data in combination with hdWGCNA, providing a new theoretical basis and research direction for molecular typing and diagnosis of OA.

Cole-Carpenter syndrome (CCS) is a rare autosomal-dominant genetic disease characterized by craniosynostosis, ocular proptosis, hydrocephalus, distinctive facial features, and bone fragility. Previous cases of CCS are associated with genetic variations in P4HB, which encodes the protein disulfide isomerase (PDI), a key enzyme in protein folding. Patients with CCS caused by P4HB mutations often present with short stature, limb deformities, and abnormal epiphyseal plates. However, the underlying mechanisms are largely unknown. To investigate this, a mouse model expressing the P4hbC402R mutation (corresponding to P4HBC400R in humans) was generated. Although the mouse model did not exhibit craniofacial bone defects or brittle bone phenotypes, it did show significantly shortened long bones—a prominent characteristic of P4HB-induced CCS. This was due to impaired proliferation and delayed hypertrophy of growth plate chondrocytes. Mutant PDI was found to accumulate abnormally in the endoplasmic reticulum (ER), and in vitro experiments revealed defects in both the catalytic and chaperone activities of mutant PDI. In addition, we observed enhanced ER stress and activation of the PKR-like ER kinase (PERK) pathway in P4hbC402R/+ chondrocytes. Inhibition of ER stress mitigated PERK activation, alleviated defective chondrocyte proliferation and differentiation, thereby rescuing bone length. Taken together, enhanced ER stress and the activation of the PERK, potentially initiated by the malfunctioning of PDIC402R or its abnormal accumulation within the ER, or both, lead to compromised chondrocyte proliferation and differentiation in mice, and ultimately stunts mice growth. This provides new insights into the pathogenesis of P4HB-dominated CCS and offers potential therapeutic targets.

Osteosarcopenia, characterized by the coexistence of osteopenia/osteoporosis and sarcopenia, represents a significant health concern in geriatrics, with an increased risk of falls and fractures. The enterokine fibroblast growth factor 19 (FGF19) was recently shown to prevent muscle weakness in preclinical models. This study investigated the therapeutic potential of FGF19 in mitigating bone and muscle deterioration in aged male mice. Twenty-one-month-old C57BL/6 male mice received daily injections of human recombinant FGF19 (0.1 mg/kg) for 21 days. Histological and functional analyses revealed a shift toward larger muscle fibers in FGF19-treated mice as well as an increased muscle strength, without affecting muscle mass. In parallel, X-ray microtomography showed that FGF19 had no overt negative impact on bone, with a range of modest, site-specific, and opposing effects. In the distal femur metaphysis FGF19, it reduced cortical thickness, but significantly increased bone cross-sectional area, with an overall increased polar moment of inertia, a geometrical parameter linked to favorable mechanical properties. It also elevated cortical bone porosity in the same region. There were no significant effects on trabecular bone or cortical bone parameters in the proximal femur side at the lesser trochanter level nor at the femoral midshaft or in the tibia. In the L2 vertebra, cortical porosity decreased. Histomorphometry of trabecular bone and analysis of transcriptional output of selected genes in femurs revealed only minor changes in bone cellular activities and gene expression after three weeks of treatment. In conclusion, FGF19 treatment increased muscle strength in aged male mice, without negatively impacting aging bone.

To date, monthly oral bisphosphonates have not been available in China. In this randomized, double blind, positive-controlled, multicenter phase III clinical trial, we compared the efficacy and safety of monthly minodronate versus weekly alendronate in the treatment of Chinese postmenopausal women with osteoporosis. A total of 548 participants were screened across 31 study centers, of which 330 participants were randomized into two groups: the experimental group (n = 165) received oral minodronate (50 mg/tablet once every four weeks) and alendronate placebo (once weekly), while the positive control group (n = 165) received oral alendronate (70 mg/tablet once weekly) and minodronate placebo (once every four weeks) for a duration of 48 weeks. The bone mineral density (BMD) of the lumbar spine, femoral neck and total hip were measured using dual-energy X-ray absorptiometry (DXA) at baseline and at 24 and 48 weeks. At the end of treatments, the experimental group exhibited a mean increase (SD) in BMD above the baseline at the lumbar spine, femoral neck and total hip of 4.61% (4.613%), 3.04% (4.034%) and 3.40% (3.569%), respectively, compared with those of 4.55% (3.753%), 1.86% (3.592%) and 2.30% (4.838%) in the control group. All improvements from the baseline in the two groups were statistically significant. The monthly minodronate did not cause new safety risks compared with alendronate. This study demonstrates that monthly minodronate administration is non-inferior to weekly alendronate in terms of therapeutic efficacy, while maintaining a comparable safety profile. Furthermore, the monthly dosing schedule of minodronate may significantly enhance medication adherence among osteoporosis patients, potentially improving long-term treatment outcomes.

ObjectiveStudies on the baseline vitamin D levels in osteogenesis imperfecta (OI) patients before medication are scarce. This study assessed the vitamin D status of a population with OI at both the overall level and within different age groups. It correlated baseline 25-hydroxyvitamin D (25(OH)D) levels with other bone-related factors, biochemical markers, and bone density.Patients and methodsWe collected 25(OH)D levels from 95 OI patients in East China (59 under 18 years old and 36 over 18 years old). Postmenopausal women and men over 50 years old are excluded. Measurements included body indicators, biochemical markers, and bone mineral density (BMD) assessed by Dual-energy X-ray absorptiometry (DXA). Data analysis was performed using SPSS 26.0.ResultsIn the overall population, among those under 18 years old, and among those over 18 years old, 87.4, 83.1, and 94.4%, respectively, were vitamin D deficient (<30 ng/mL), while 47.4, 40.7, and 58.3% had vitamin D deficiency (<20 ng/mL), respectively. In the overall population and among those under 18 years old, serum 25(OH)D levels were negatively correlated with age and parathyroid hormone (PTH) levels, and 25(OH)D levels (<10 ng/mL, 10–20 ng/mL, 20–30 ng/mL, >30 ng/mL) showed a negative correlation with BMI. In OI patients under 18 years old, serum 25(OH)D was negatively correlated with serum β-CTX levels. In adult male OI population, 25(OH)D levels were negatively correlated with OI severity (Type I, IV, III). No statistically significant correlation was found between 25(OH)D levels and BMD Z-scores.ConclusionThis study on OI in East China reveals significant vitamin D insufficiency and deficiency in baseline levels among pediatric, adolescent and adult OI patients. It assesses the correlation of 25(OH)D levels with various influencing factors, providing crucial insights into understanding the impact of OI on vitamin D status across different age groups and aiding in better clinical management of OI patients.