Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA最新文献

{"title":"The incidence and predictors of falling in older adults: the results of follow-up in Iranian multicenter osteoporosis study (IMOS).","authors":"Mohammad Ahmadi, Maral Sargolzaeimoghaddam, Vahideh Mohseni, Mohammad Sargolzaeimoghaddam, Kazem Khalagi, Mohammad Javad Mansourzadeh, Samaneh Akbarpour, Gita Shafiee, Mahnaz Sanjari, Noushin Fahimfar, Afshin Ostovar","doi":"10.1007/s00198-026-08183-3","DOIUrl":"https://doi.org/10.1007/s00198-026-08183-3","url":null,"abstract":"<p><p>In this prospective cohort of 1,410 community-dwelling Iranian older adults, a history of falls in the previous year was the strongest independent predictor of incident falls over one-year follow-up, supporting routine fall-history assessment as part of fracture-risk stratification.</p><p><strong>Background: </strong>Osteoporosis and falls are closely interlinked, particularly among aging populations, leading to increased risks of fragility fractures and disability. Identifying fall-related risk factors is essential for guiding prevention strategies.</p><p><strong>Objective: </strong>This study aimed to investigate the incidence of falls and associated risk factors among community-dwelling older adults in Iran over a one-year follow-up period.</p><p><strong>Methods: </strong>Individuals aged ≥ 50 years, who participated in the Iranian Multicenter Osteoporosis Study were followed. Baseline data included demographics, medical history, functional assessments, and laboratory findings. Falls were tracked prospectively over 12 months through phone calls. Statistical analyses included chi-square tests for categorical variables, independent t-tests for numerical comparisons, and Cox proportional hazards regression to identify predictors of falls. Variables with p < 0.20 in univariable analyses were entered into the multivariable model.</p><p><strong>Results: </strong>Among 1,450 participants at baseline, 1,410 (54.6% women; mean age 60.7 ± 8.0 years) completed follow-up. The overall fall incidence rate was 14.27 per 1,000 person-years (95% CI: 12.64-16.09), with higher rates among women than men. In unadjusted analyses, female sex, higher BMI, dizziness, visual impairment, and prior fall history were associated with increased fall risk. After multivariable adjustment, a history of one fall during past year (HR:2.49, 95%CI:1.76-3.70), two or more falls during past year (HR:2.55, 95%CI:1.74-3.70) and visual impairment (HR:1.48,95%CI:1.05-2.08) remained independent predictors of incident falls. Those with a fall in the previous year showed more than a 2.7-fold higher risk of subsequent falls (HR = 2.70; 95% CI: 1.99-3.66; p < 0.001).</p><p><strong>Conclusion: </strong>History of previous falls was the important independent predictor of incident falls after adjustment, highlighting the importance of systematic fall-history assessment in community-dwelling older adults.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends and disparities in DXA testing for osteoporosis among Medicare beneficiaries, 2005-2023.","authors":"Casey E Pelzl, Anand K Narayan, Tyler M Prout, Neil C Binkley, Tarig Elhakim, Taha Lodhi, Alexandra Drake, Elizabeth Y Rula, Eric W Christensen, Dania Daye","doi":"10.1007/s00198-026-08083-6","DOIUrl":"https://doi.org/10.1007/s00198-026-08083-6","url":null,"abstract":"<p><p>DXA utilization among Medicare beneficiaries declined 35% from 2005 to 2023. Declines were disproportionately larger among racial/ethnic minorities and socioeconomically deprived groups, while use increased among highest-acuity patients. These findings highlight widening inequities in DXA testing and underscore the need for targeted policy and public health interventions.</p><p><strong>Objective: </strong>The objective of this study is to examine the association between demographic and socioeconomic (SES) factors and national trends in dual-energy X-ray absorptiometry (DXA) testing among Medicare beneficiaries.</p><p><strong>Methods: </strong>This 19-year repeated cross-sectional study used 5% Medicare fee-for-service claims (2005-2023) to assess the annual utilization of DXA. Claims missing patient ZIP code, age, or race/ethnicity were excluded. Patient acuity was measured using the Neiman Imaging Comorbidity Index (NICI). Patient residence ZIP codes were used to determine urbanicity and Area Deprivation Index. Annual DXA utilization was calculated per 100,000 beneficiaries overall and stratified by SES covariates. Covariate associations with DXA utilization were assessed using logistic regression and comparisons of adjusted odds ratios (AOR) between years quantified utilization changes.</p><p><strong>Results: </strong>We identified 5,243,098 unique beneficiaries from 2005 to 2023 (mean 2,517,265 beneficiaries per year); 1,218,904 (23.2%) beneficiaries had at least one DXA. Annual use per 100,000 beneficiaries declined 35.4% from 7255 in 2005 to 4,690 in 2023. Hispanic beneficiaries saw the largest percentage decrease (-35.3%) in AOR of DXA utilization from 2005 (AOR, 0.93) to 2023 (AOR, 0.60), while beneficiaries with NICI ≥ 7 demonstrated the largest percentage increase (+57.7%) in AOR of DXA utilization from 2005 (AOR, 1.11) to 2023 (AOR, 1.70).</p><p><strong>Conclusions: </strong>Underserved populations have seen greater declines in DXA utilization compared with the observed national decline from 2005 to 2023. Future studies should identify the underlying factors associated with these disparities to inform public health interventions that enhance equitable utilization of DXA testing across the nation.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis.","authors":"Leonhard S Hummel, Martina Blaschke, Annette Lamersdorf, Gabriele Lehmann, Uwe Kornak, Heide Siggelkow","doi":"10.1007/s00198-026-08161-9","DOIUrl":"https://doi.org/10.1007/s00198-026-08161-9","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) occurs in patients referred for suspected osteoporosis. In our cohort, ALP below 25 IU/L predicted a positive genetic diagnosis, yet higher values did not rule out the clinical diagnosis of HPP. Lower ALP correlated with increased fracture risk independent of genetic results, underscoring the clinical importance of recognising HPP to prevent use of contraindicated treatments.</p><p><strong>Purpose: </strong>Hypophosphatasia (HPP) is a rare inherited metabolic disorder affecting bone and teeth, characterised by osteomalacia, stress fractures, and pseudofractures. It remains underdiagnosed and may coexist with osteoporosis, risking inappropriate anti-resorptive therapy. This study characterised the biochemical, clinical, and densitometric features of adults with low alkaline phosphatase (ALP) and identified predictors of genetically confirmed HPP.</p><p><strong>Methods: </strong>We retrospectively analysed adults referred to our centre for thyroid, endocrine, osteoporosis, or rheumatological conditions in whom low ALP was identified. Data extracted included fracture history, dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), biochemical parameters including pyridoxal-5-phosphate (PLP), and ALPL variant testing. ALPL-positive and ALPL-negative groups were compared using regression analyses.</p><p><strong>Results: </strong>Of 33 patients, 20 carried pathogenic ALPL variants. All individuals with ALP ≤ 25 IU/L had a detectable disease-causing variant, though ALP was often higher in variant-positive patients. PLP levels differed significantly between groups, whereas bone-specific ALP, standard biochemical markers, and DXA T-scores did not. Overall fracture prevalence was similar between groups; however, each 7.8 IU/L decrease in ALP significantly increased fracture probability, independent of genotype. Peripheral fractures predominated, consistent with adult HPP. One patient received bisphosphonates before diagnosis.</p><p><strong>Conclusion: </strong>Very low ALP strongly indicates HPP, yet the clinical spectrum extends beyond strict biochemical thresholds. ALP level-independent of genetic status-predicts fracture risk, suggesting residual enzyme activity is clinically relevant. These findings highlight the limitations of DXA and FRAX in HPP and underscore the need for thorough biochemical evaluation and broader clinical awareness to prevent contraindicated osteoporosis treatments.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smartphone-based patient-reported outcome of acute phase reaction after zoledronic acid infusion and prediction algorithm: a multicenter, prospective cohort study.","authors":"Sung Joon Cho, Sang Wouk Cho, Min Heui Yu, Seng Chan You, Seong Hee Ahn, Yumie Rhee, Namki Hong","doi":"10.1007/s00198-026-08172-6","DOIUrl":"https://doi.org/10.1007/s00198-026-08172-6","url":null,"abstract":"<p><p>Acute phase reaction (APR) after zoledronic acid infusion impairs adherence and treatment outcomes. Using smartphone-based ePRO monitoring, we developed a simple prediction model for severe APR incorporating age, sex, and day-1 symptoms. This algorithm showed good discrimination and may enable early identification and personalized prevention of severe APR.</p><p><strong>Purpose: </strong>Zoledronic acid (ZOL) is an effective antiresorptive therapy for osteoporosis, but acute phase reaction (APR) after initial infusion may impair adherence and outcomes. Identifying individuals at high risk for severe APR is essential for personalized prevention.</p><p><strong>Methods: </strong>This multicenter, prospective observational study collected electronic patient-reported outcome (ePRO) data via a smartphone application after a single 5-mg ZOL infusion. Adults aged ≥ 19 years reported the severity of nine APR symptoms daily for four days using a 5-point scale. Daily scores were summed to calculate a total APR score. Severity was categorized as mild-to-moderate or severe based on the median of total APR score. A prediction algorithm for severe APR was developed using age, sex, and day-1 symptoms.</p><p><strong>Results: </strong>Among 685 participants (mean age 70.6 years; 83.7% women), 222 (32.4%) experienced APR, and 118 (17.2%) developed severe APR. APR scores peaked on day 2 and declined by day 4. Severe APR showed earlier onset, longer duration, and greater symptom burden than mild-to-moderate APR. Younger age and female sex were associated with severe APR. Five day-1 symptoms (myalgia, arthralgia, chills, headache, and back pain) were identified as core predictors. A compact model incorporating age, sex, and the number of day-1 core symptoms demonstrated good discrimination for severe APR (AUROC 0.81).</p><p><strong>Conclusion: </strong>Smartphone-based ePRO effectively captured APR severity following ZOL. A simple clinical algorithm using age, sex, and day-1 symptoms accurately identified individuals at high risk for severe APR, enabling personalized preventive strategies.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author response to original letter, manuscript no. OSIN-D-26-01474, \"Pre-teriparatide anti-osteoporosis medication therapy and fracture-related hospitalization in patients at very high fracture risk\".","authors":"Shao-Chi Fu, Chen-Yu Wang, Shau-Huai Fu","doi":"10.1007/s00198-026-08173-5","DOIUrl":"10.1007/s00198-026-08173-5","url":null,"abstract":"","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2155-2156"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased fracture risk associated with iron-deficiency anemia: a population-based propensity score matched cohort study.","authors":"Andrea M Burden, Adrian Martinez-De la Torre, Maria Immoos, Theresa Burkard, Lorenz C Hofbauer, Martina Rauner, Andrea U Steinbicker","doi":"10.1007/s00198-026-08002-9","DOIUrl":"10.1007/s00198-026-08002-9","url":null,"abstract":"<p><p>Anemia seems to be associated with an increased risk of fracture. This cohort study of the UK primary care data shows in 84,932 anemic patients and 158,731 controls an increased fracture risk in anemic patients, also including patients < 50 years of age. Severe anemia was associated with 2 × vertebral fracture risk. Awareness of this clinically relevant association should increase.</p><p><strong>Purpose: </strong>In this study, we evaluated the risk of fracture among adult patients with anemia, compared to propensity score matched controls, stratifying by fracture site, age, and severity of anemia.</p><p><strong>Methods: </strong>We conducted a cohort study using the UK IQVIA Medical Research Database (IMRD), incorporating The Health Improvement Network (THIN), a Cegedim database. Adults with a diagnosis of anemia and an eligible hemoglobin value (< 13 g/dL (men) or < 12 g/dL (women)) were matched to controls using propensity score matching. Cox proportional hazard models estimated the hazard ratios (HRs) for the risk of any fracture (stratified by fracture site, sex, and age (defined < 50 years and >  = 50 years)).</p><p><strong>Results: </strong>84,932 anemic patients were matched to 158,731 controls. Overall, anemia was associated with a significant 20% risk of any fracture (driven by a 32% (HR 1.32, 1.20-1.47) increase among males, no difference among females). When stratified by sex, males had a significant risk at all fracture sites (27% (HR 1.27, 1.03-1.58) risk for vertebral, 89% (HR 1.89, 1.52-2.34) risk for humerus fractures). In females, only hip (HR 1.14, 1.05-1.25) and vertebral fractures (HR 1.24, 1.07-1.43) were significantly associated with anemia. Patients ≥ 50 years had elevated risks for all sites. In patients < 50 years, only hip fracture was elevated (HR 1.86, 1.04-3.33).</p><p><strong>Conclusion: </strong>Anemia was associated with a significant 20% increase of any fracture; however, this was driven by the elevated risk among males and those over the age of 50 years. Among females, only hip and vertebral fracture risk was elevated, while males had an elevated risk at all sites.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2037-2049"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative denosumab exposure and risk of revision after total hip and knee arthroplasty in osteoarthritis: a registry-based data linkage study.","authors":"Jacopo Ciaffi, Barbara Bordini, Monica Cosentino, Gherardo Mazziotti, Roberto Caporali, Alberto Di Martino, Cesare Faldini, Linda Russell, Susan M Goodman, Francesco Ursini","doi":"10.1007/s00198-026-08040-3","DOIUrl":"10.1007/s00198-026-08040-3","url":null,"abstract":"<p><p>Osteoarthritis patients undergoing THA or TKA were studied to compare the cumulative incidence of revision after perioperative denosumab versus alendronate. Denosumab was not associated with differences in the incidence of revision after THA but was associated with a higher revision incidence after TKA, mainly driven by aseptic tibial loosening.</p><p><strong>Background: </strong>Osteoarthritis is highly prevalent, and the number of total hip (THA) and knee arthroplasties (TKA) continues to rise. This study aimed to evaluate the risk of revision associated with perioperative exposure to denosumab versus alendronate in patients undergoing THA or TKA for osteoarthritis.</p><p><strong>Methods: </strong>This retrospective cohort study used data from the Emilia-Romagna Registry of Orthopedic Prosthetic Implants (RIPO). Patients undergoing primary THA or TKA for osteoarthritis between 2011 and 2023 were included. Perioperative exposure was defined as at least one dispensing of denosumab or alendronate within 180 days before or after surgery. The primary outcome was first revision. Revision risk was analysed using cumulative incidence functions, treating death and emigration as competing events, and groups were compared using Gray's test.</p><p><strong>Results: </strong>The THA cohort comprised 129 denosumab and 922 alendronate users. Revision occurred in 4 denosumab (3.1%) and 21 alendronate patients (2.3%); no significant difference was observed in competing risk analyses (Gray's p = 0.623). In the TKA cohort, 117 denosumab and 940 alendronate users were analysed. Here 8 denosumab patients (6.8%) and 18 alendronate patients (1.9%) required revision, with a significant difference in cumulative incidence (Gray's p = 0.002). Revisions in denosumab users were mainly due to aseptic tibial loosening.</p><p><strong>Conclusions: </strong>Perioperative denosumab exposure was associated with a higher cumulative incidence of revision after TKA in this cohort. These findings should be interpreted cautiously and do not imply causality. The observed pattern may reflect complex interactions between antiresorptive therapy and joint-specific biomechanical factors, which warrant further investigation.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2005-2016"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the clinical utility of calcium isotopes: from static screening to dynamic monitoring.","authors":"Ningyou Hu","doi":"10.1007/s00198-026-08105-3","DOIUrl":"10.1007/s00198-026-08105-3","url":null,"abstract":"","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2167"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hip response to romosozumab in glucocorticoid users: beyond systemic bone turnover markers.","authors":"Kaiquan Zhang, Meng Zhao, Dongdong Li","doi":"10.1007/s00198-026-08114-2","DOIUrl":"10.1007/s00198-026-08114-2","url":null,"abstract":"","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2141-2142"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of hypophosphatasia in adults with persistent hypophosphatasemia: clinical-genetic characterization and a validated diagnostic tool.","authors":"Yazhao Mei, Ziyuan Wang, Na Ren, Li Shen, Xiang Li, Hua Yue, Hao Zhang, Jiemei Gu, Weiwei Hu, Jie Wang, Shanshan Li, Chao Gao, Zhe Wei, Yang Xu, Shuqin Xu, Wei Hong, Qiongyao Shi, Ya Wang, Jing Xu, Gao Gao, Zhenlin Zhang, Chun Wang","doi":"10.1007/s00198-026-07986-8","DOIUrl":"10.1007/s00198-026-07986-8","url":null,"abstract":"<p><p>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.</p><p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":520737,"journal":{"name":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":" ","pages":"2051-2062"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}