Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Heterogeneous Origins of Calcium Homeostasis Disorders Arising From 5 Heterozygous Calcium-Sensing Receptor Variants.","authors":"Wei Du, Ida Marie Boisen, Sabrina N Rahman, Nadia Nicholine Poulsen, Jesper M Mathiesen, Martin Blomberg Jensen, Hans Bräuner-Osborne, Anders A Jensen","doi":"10.1210/clinem/dgae735","DOIUrl":"10.1210/clinem/dgae735","url":null,"abstract":"<p><strong>Context: </strong>The human calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and most identified CASR variants are associated with hypercalcemic and hypocalcemic disorders.</p><p><strong>Objective: </strong>Here we characterized the pharmacological implications of 5 heterozygous CASR variants from individuals with familial hypocalciuric hypercalcemia 1 (FHH1: Y63C, I81T, Q459R, W818stop) or autosomal dominant hypocalcemia 1 (ADH1: R955stop).</p><p><strong>Methods: </strong>Total and cell surface expression levels of wild-type (WT) and variant CaSRs expressed in human embryonic kidney 293T (HEK293T) cells were determined using enzyme-linked immunosorbent assay, and the pharmacological properties of the receptors were delineated in 2 functional assays.</p><p><strong>Results: </strong>The Y63C and I81T variations in the extracellular domain (ECD) of CaSR yielded markedly reduced cell surface expression and Ca2+ responsiveness, while Q459R displayed WT-like expression and functional properties. Truncation of the 7-transmembrane domain (7TMD) in W818stop eliminated cell surface expression, whereas R955stop in the intracellular carboxy-terminal yielded modestly increased surface expression and Ca2+ potency compared with WT CaSR. Interestingly, the effectiveness of positive allosteric modulators (PAMs) at the variants varied. Ca2+-mediated signaling through Y63C and I81T was significantly augmented by 7TMD-binding PAMs (NPS R-568 and evocalcet) but not by ECD-binding PAMs (etelcalcetide and Nb4), whereas signaling through Q459R and R955stop were robustly potentiated by all four PAMs.</p><p><strong>Conclusion: </strong>While the molecular phenotypes exhibited by the 5 CaSR variants concord with the clinical phenotypes in individuals harboring them, CASR variant-induced calcium homeostasis disorders clearly arise from diverse molecular origins, and the effectiveness of calcimimetics in these disorders could differ depending on the specific variants.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1865-1880"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial Stiffness Associated With Long-term Major Adverse Cardiac Events in Patients With Primary Aldosteronism.","authors":"Vin-Cent Wu, Wen-Kai Chu, Po-Lung Yang, Yen-Hung Lin, Shuo-Meng Wang, Jeff S Chueh","doi":"10.1210/clinem/dgae683","DOIUrl":"10.1210/clinem/dgae683","url":null,"abstract":"<p><strong>Context: </strong>As a novel parameter for risk prediction, artery stiffness may hold promise in refining risk assessment strategies, guiding therapeutic interventions, and ultimately improving cardiovascular outcomes in patients with primary aldosteronism (PA).</p><p><strong>Objective and methods: </strong>To investigate the correlation between brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, and the occurrence of major adverse cardiovascular events (MACEs) in patients with PA under a primary prevention design.</p><p><strong>Results: </strong>Among the 830 patients included in the final analysis, 113 (13.6%) developed incident MACEs over a median follow-up period of 5.8 years, with a crude rate of 23.2 per 1000 person-years. Multivariable Cox proportional hazards analyses revealed that baPWV was an independent risk factor for incident MACEs, with an adjusted hazard ratio (HR) of 1.01 (P = .028). The generalized additive model identified a cut-off value of 2000 cm/s for baPWV, which was independently associated with incident MACEs, with a HR of 1.81 (P = .024), while accounting for mortality as a competing risk. Subgroup analyses revealed that PA patients who were mineralocorticoid receptor antagonist users and had high baPWV had a significantly higher risk of incident MACEs (HR = 3.34; P < .001), whereas the risk was not significant in patients who underwent adrenalectomy (P = .062). Furthermore, the addition of baPWV to the cardiovascular Framingham risk score significantly improved the category-free net reclassification index (0.308, P < .001).</p><p><strong>Conclusions: </strong>Our study found that 13.6% of patients with PA developed MACEs after a median follow-up of 5.8 years. Our findings highlight the potential utility of baPWV as a tool for risk stratification in patients with PA in primary prevention, whereas adrenalectomy appears to mitigate this risk regardless of baPWV. The measurement of baPWV could be a valuable addition to hypertension screening programs for primary prevention, providing additional predictive information for the potential occurrence of MACEs.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1896-1905"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Management of Complications of Laser Ablation for Benign Thyroid Nodules.","authors":"Lorenzo Scappaticcio, Nicole Di Martino, Pamela Ferrazzano, Maria Ida Maiorino, Paola Caruso, Alessandra Volatile, Miriam Longo, Giovanni Docimo, Eduardo Iervolino, Pierpaolo Trimboli, Katherine Esposito, Giuseppe Bellastella","doi":"10.1210/clinem/dgaf108","DOIUrl":"10.1210/clinem/dgaf108","url":null,"abstract":"<p><strong>Context: </strong>Percutaneous laser ablation (LA) is today regarded as a valuable therapy for symptomatic, benign solid (noncystic) thyroid nodules (STNs).</p><p><strong>Objective: </strong>We assessed the prevalence of complications from LA for benign and STNs and their management.</p><p><strong>Methods: </strong>We conducted a systematic review with meta-analysis of data from published studies on LA of STNs, in addition to author institutions. A random effects meta-analysis was performed on the prevalence rates.</p><p><strong>Results: </strong>The literature search yielded 1351 studies, of which 38 studies were included, in addition to our institutional experience (4745 STNs in total). The overall quality of each included study was judged as fair. The prevalence of \"overall\" complications of LA was 23% ([CI, 17%-30%], I2 93.7%, 1208 of 4702 thyroid nodules [TNs]). The prevalence of \"minor\" complications of LA was 21% ([CI, 15%-27%], I2 93.7%, 1159 of 4702 TNs). The prevalence of \"major\" complications of LA was 2% ([CI, 1%-3%], I2 54.0%, 49 of 4745 TNs). Sensitivity analyses did not modify the results, except for dysphonia, whose pooled prevalence was higher when using local anesthesia (2%; CI, [1%-3%], I2 25.2; P = .010) or conscious sedation (2%; CI, [1%-4%], I2 27.2; P = .014). The pooled prevalence rate of local pain was 15% (CI, [12%-20%], I2 89.3). Local pain was transient and typically mild to moderate, sometimes severe, requiring analgesics for 1 to 5 days up to 1 month. The pooled prevalence rate of dysphonia was 2% (CI, [1%-2%], I2 30.3). All cases of dysphonia were transient except for one permanent case.</p><p><strong>Conclusion: </strong>LA for benign and noncystic STNs can be considered a generally safe technique. Major complications are rare.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2383-e2396"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Practices in Monitoring Children and Adults With X-linked Hypophosphatemia: A Global Survey of Expert Experience.","authors":"Dalal S Ali, Farah Alsarraf, Hajar Abu Alrob, R Todd Alexander, Abdulrahman Almoulia, Natasha M Appelman-Dijkstra, Signe Sparre Beck-Nielsen, Martin Biosse-Duplan, Maria Luisa Brandi, Thomas O Carpenter, Catherine Chaussain, Martine Cohen-Solal, Rachel K Crowley, Karel Dandurand, Pablo Florenzano, Claudia Gagnon, Paul Goodyer, Chelsey Grimbly, Salma Hussein, Erik A Imel, Suzanne M Jan de Beur, Muhammad K Javaid, Anna Lehman, Willem F Lems, E Michael Lewiecki, Ciara McDonnell, Reza D Mirza, Emmett Morgante, Anthony A Portale, Yumie Rhee, Heide Siggelkow, Laura L Tosi, Leanne M Ward, Gordon Guyatt, Aliya A Khan","doi":"10.1210/clinem/dgaf180","DOIUrl":"10.1210/clinem/dgaf180","url":null,"abstract":"<p><p>This report provides recommendations for X-linked hypophosphatemia (XLH) monitoring based on current monitoring practices of experts in the management of XLH in children (<18 years) and adults. We surveyed 43 international experts in XLH to determine their monitoring practices for children and adults with XLH, including pregnant and lactating women. In the initial evaluation of children and adults with XLH, experts consistently obtain a family history of XLH or hypophosphatemia, a history of fractures and dental infections, and assess pain through age-appropriate clinical interviews or caregiver reports. They measure height, weight, and blood pressure and conduct DNA analysis of multiple genes associated with hypophosphatemia including the PHEX gene. For children follow-up, experts arrange follow-up every 3 to 6 months assessing height, weight, and blood pressure and examining for skeletal deformities. Laboratory tests in children include serum phosphorus, corrected total/ionized calcium, alkaline phosphatase, renal function, and PTH and spot morning urine for calcium, creatinine, and phosphorus. During adult follow-up, experts assess patients every 6 to 12 months, with a clinical examination focused on skeletal deformities and joint involvement. The laboratory profile is completed at least once a year. In the presence of bone pain, experts conduct X-rays both in children and adults to evaluate for fractures or joint damage. With respect to nephrocalcinosis, renal ultrasound is suggested on an annual basis or less frequently when monitoring children and adults with XLH. Experts conduct a dental assessment at baseline and then every 6 to 12 months for all patients with XLH. The findings of the survey inform practice for assessing new patients with XLH, monitoring existing patients, and identifying areas for future research. All recommendations based on these practices are weak with very low-quality evidence.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2347-e2361"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylglyoxal Mediates the Association Between 2-Hour Plasma Glucose and HbA1c With Inflammation: The Maastricht Study.","authors":"Dijia Sun, Marleen M J van Greevenbroek, Jean L J M Scheijen, Jaycey Kelly, Casper G Schalkwijk, Kristiaan Wouters","doi":"10.1210/clinem/dgae640","DOIUrl":"10.1210/clinem/dgae640","url":null,"abstract":"<p><strong>Context: </strong>Glucose excursions in persons with diabetes may drive chronic inflammation. Methylglyoxal (MGO) is formed from glucose, is elevated in persons with diabetes, and is a potent glycating agent linked with inflammation.</p><p><strong>Objective: </strong>We investigated whether glucose excursions are associated with low-grade inflammation and whether MGO mediates this association.</p><p><strong>Methods: </strong>We used data from The Maastricht Study, an extensive phenotyping study into the etiology of type 2 diabetes and its complications. Data of 3017 participants, who underwent an oral glucose tolerance test and where data on MGO levels and inflammation were available, were used. Linear regression analyses, adjusted for potential confounders, evaluated associations between fasting plasma glucose (FPG), 2-hour plasma glucose (2h-PG) and HbA1c, and low-grade inflammation (stdβ, [95% CI]) were calculated from plasma concentrations of C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, tumor necrosis factor, and soluble intercellular adhesion molecule-1. Mediation analyses investigated whether MGO mediated these associations.</p><p><strong>Results: </strong>2h-PG (0.172, [0.110; 0.234]) and HbA1c (0.148, [0.101; 0.196]), but not FPG (0.049, [-0.002; 0.100]), were associated with low-grade inflammation. 2h-PG and HbA1c were also associated with 2h-MGO (0.471, [0.407; 0.534], and 0.244, [0.195; 0.294], respectively). Furthermore, 2h-MGO was independently and positively associated with low-grade inflammation (0.078, [0.037; 0.120]). 2h-MGO mediated 23% of the association between 2h-PG and inflammation, and 16% of the association between HbA1c and inflammation.</p><p><strong>Conclusion: </strong>MGO mediates the association between postload glucose excursions and HbA1c with inflammation, providing evidence for a role of postprandial MGO formation to hyperglycemia-induced low-grade inflammation.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2047-2054"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Reduction of Subclinical Inflammation in the Years After Breastfeeding.","authors":"Miya Boelling, Jiajie Pu, Anthony J Hanley, Philip W Connelly, Mathew Sermer, Bernard Zinman, Ravi Retnakaran","doi":"10.1210/clinem/dgae772","DOIUrl":"10.1210/clinem/dgae772","url":null,"abstract":"<p><strong>Context: </strong>Lactation is associated with lower future risk of cardiovascular disease (CVD) in women but the mechanism(s) underlying this relationship remain unclear.</p><p><strong>Objective: </strong>We sought to characterize the relationship between duration of exclusive breastfeeding and CV risk factors over the first 5 years post partum.</p><p><strong>Methods: </strong>In this prospective cohort study, 328 women underwent serial cardiometabolic characterization (anthropometry, blood pressure [BP], lipids, fasting glucose, adiponectin, C-reactive protein [CRP]) at 1 year, 3 years, and 5 years post partum. Outcomes were CV risk factors in 3 groups defined by duration of exclusive breastfeeding: less than 3 months (n = 107), 3 to 6 months (n = 101), and 6 months or more (n = 120).</p><p><strong>Results: </strong>The prevalence of metabolic syndrome did not differ between the groups at 3 years but, by 5 years post partum, was higher in women who had exclusively breastfed for less than 3 months than in those who did so for 3 to 6 and 6 months or more, respectively (14.0% vs 6.9% vs 4.2%; P = .02). However, after adjustment for covariates (including body mass index [BMI]), there were no statistically significant differences between groups in BP, glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, or adiponectin. Indeed, the only CV risk factor difference that persisted after covariate adjustment was that women who had exclusively breastfed for less than 3 months had higher CRP both at 3 years (P = .04) and 5 years (P = .01). Moreover, generalized estimating equation analyses with adjustment for covariates (including time-dependent BMI) showed that CRP remained higher over time in these women, as compared to their peers, from 1 year to 3 years to 5 years post partum (P = .03).</p><p><strong>Conclusion: </strong>Sustained reduction of subclinical inflammation may contribute to the cardioprotective effect of lactation in women.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2208-e2216"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Balance Measures and Risk of Fractures in 70-Year-Old Individuals.","authors":"Peter Nordström, Marcel Ballin, Anna Nordström","doi":"10.1210/clinem/dgae766","DOIUrl":"10.1210/clinem/dgae766","url":null,"abstract":"<p><strong>Context: </strong>There are uncertainties regarding to what extent poor vision and distracting tasks reduce balance and are associated with fracture risk.</p><p><strong>Objective: </strong>This work aimed to investigate the associations between body sway assessed under different visual and multitasking conditions and later risk of fractures in older adults.</p><p><strong>Methods: </strong>This cohort study was conducted in Umeå municipality, Sweden. A total of 5437 community-dwelling 70-year-old individuals participated in a population-based health examination. Body sway at baseline was measured using a Wii balance board in the lateral and anterior-posterior direction during 3 different tests, including with eyes open, dual-tasking, and eyes closed. Fractures during follow-up were ascertained using nationwide registers.</p><p><strong>Results: </strong>During a mean (range) follow-up of 4.8 (0.0-10.6) years, 348 women (12.3%) and 149 men (5.7%) sustained a fracture. In women, both anterior-posterior sway velocity (hazard ratio [HR], 1.05; 95% CI, 1.01-1.08, per mm/s increase) and variation in sway velocity (HR, 1.05; 95% CI, 1.01-1.09, per SD increase) during dual-tasking testing were associated with higher risk of fracture after adjustment for covariates. During testing with eyes closed, all measures of lateral sway were associated with the risk of fracture (P < .01 for all). In men, variation in lateral (HR, 1.03; 95% CI, 1.00-1.07 per SD increase) and anterior-posterior sway velocity (HR 1.05; 95% CI, 1.01-1.10 per SD increase) during dual-tasking testing were associated with higher risk of fracture.</p><p><strong>Conclusion: </strong>Higher body sway velocity and larger variation in sway velocity were associated with a higher risk of fractures both in 70-year-old men and women, especially under more challenging testing conditions.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2256-e2263"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approach to the Patient With Thyroid Cancer: Selection and Management of Candidates for Lobectomy.","authors":"Eyal Robenshtok, Gideon Bachar, Amit Ritter","doi":"10.1210/clinem/dgae903","DOIUrl":"10.1210/clinem/dgae903","url":null,"abstract":"<p><p>Thyroid lobectomy has gained increasing popularity over the past decade as a treatment for differentiated thyroid cancer, largely due to a rise in the diagnosis of low-risk cancers and evidence showing no benefit from radioiodine in low-risk disease. Multiple studies have confirmed lobectomy as an effective and safe option. Its advantages over total thyroidectomy include lower complication rates and a reduced need for lifelong levothyroxine (LT4) therapy. Recent research has broadened the indications for lobectomy, extending its use to patients with contralateral benign nodules and several \"adverse\" histological features, such as minimal extrathyroidal extension, small lymph node metastases, or multifocality-provided these are of minimal size. For patients with follicular thyroid carcinoma, who typically undergo surgery for Bethesda III-IV cytology, minimally invasive disease should be treated with lobectomy alone. In patients with angioinvasion, the risk of metastasis increases with the number of vessels involved (>2-3 vessels), larger tumor size, and advanced patient age. Following surgery, current evidence supports a TSH target within the normal range, reducing the need for LT4 treatment to only 30% of patients. Follow-up is based on neck ultrasound because thyroglobulin levels have limited value in detecting recurrence. In cases where further treatment is required, completion thyroidectomy is as safe as upfront total thyroidectomy. Overall, lobectomy is the preferred treatment option for many, if not most, differentiated thyroid cancer patients with low to low-intermediate risk disease, offering lower complication rates, reduced need for LT4 therapy, and excellent long-term outcomes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2327-e2337"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: \"Pituitary Apoplexy: Comorbidities, Management, and Outcomes-A Spanish Observational Multicenter Study\".","authors":"","doi":"10.1210/clinem/dgaf222","DOIUrl":"10.1210/clinem/dgaf222","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2432"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy of Zoledronic Acid on Fracture Reduction in Youth With Primary and Secondary Skeletal Fragility.","authors":"Ashley J Stoffers, Edna E Mancilla, Michael A Levine, Michael Mayer, Heather M Monk, Joseph Rosano, David R Weber","doi":"10.1210/clinem/dgae661","DOIUrl":"10.1210/clinem/dgae661","url":null,"abstract":"<p><strong>Context: </strong>Prior studies have demonstrated the safety and efficacy of zoledronic acid (ZA) to increase bone mineral density (BMD) in children. By contrast, the efficacy of ZA on fractures in the pediatric population remains uncertain.</p><p><strong>Objective: </strong>To investigate the effect of ZA on fracture rate in a clinical cohort of children and young adults with skeletal fragility.</p><p><strong>Methods: </strong>This retrospective cohort study, conducted at an academic medical center, included 102 individuals (65 male; 39 with primary and 63 with secondary skeletal fragility), aged 0 to 21 years, treated with ZA for skeletal fragility between 2010 and 2017. ZA was prescribed at discretion of the treating clinician using a standardized protocol. The primary outcome was change in annualized fracture rate. Secondary outcomes included long bone and spine fracture rates. Areal BMD was analyzed in a subset of individuals with dual energy x-ray absorptiometry (DXA) scans.</p><p><strong>Results: </strong>The overall median fracture rate decreased from 0.6 (IQR 0.3-1.1) to 0 (IQR 0-0.4) fractures per year, P < .001, over a median treatment duration of 1.8 (IQR 0.6-3.0) years. Significant reductions in fracture rate were observed in both primary (1.0 [IQR 0.6-1.5] to 0.3 [IQR 0-0.6]) and secondary (0.5 [IQR 0.1-0.8] to 0 [IQR 0-0.3]) forms of skeletal fragility, P < .001 for both. Significant reductions in fracture rate persisted when limited to long bone or long bone plus spine fractures.</p><p><strong>Conclusion: </strong>ZA treatment as a component of clinical care was associated with significant declines in fracture rate in this cohort of children and young adults with skeletal fragility.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2031-2040"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}