Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Anastrozole Improves Height Outcomes in Growing Children With Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency.","authors":"Heba Al-Rayess, Rebecca Wiersma, Lindsey Elizabeth Turner, Elise Palzer, Yesica Mercado Munoz, Kyriakie Sarafoglou","doi":"10.1210/clinem/dgae771","DOIUrl":"10.1210/clinem/dgae771","url":null,"abstract":"<p><strong>Background: </strong>Hyperandrogenemia resulting in estrogen-mediated accelerated bone maturation and early growth plate fusion contributes to short stature in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Aromatase inhibitors block androgen conversion to estrogen and have been used off-label in children with short stature to improve adult height. There are no adequately powered studies examining the use of aromatase inhibitors in children with CAH with advanced bone age and reduced predicted adult height.</p><p><strong>Methods: </strong>Records of CAH patients treated with anastrozole were reviewed. Z-scores of bone age, predicted adult height, and height corrected for bone age were examined over an 8-year period. Outcome changes were analyzed using weighted mixed-effects models, adjusting for sex, diagnosis, age at diagnosis, and average hydrocortisone dose before and during treatment with anastrozole.</p><p><strong>Results: </strong>In 60 patients (26 females; 52 classic, 8 nonclassic) started on anastrozole therapy, the mean bone age Z-score decreased from 4.2 to 2.0 at 4 years and 1.3 at 6 years (both P < .001); predicted adult height Z-score improved from -2.1 to -0.45 at 4 years and 0.18 at 6 years (both P < .001); corrected height Z-scores improved from -1.7 to -0.33 at 4 years and 0.18 at 6 years (P < .001). There was no significant difference in the average total daily hydrocortisone dose used before or during treatment.</p><p><strong>Conclusion: </strong>Anastrozole decreased the rate of bone maturation and led to improved height outcomes, indicating that anastrozole could have a role as an adjunct therapy in children with CAH and advanced bone age.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2198-e2207"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570045","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":"Approach to the Patient with Achondroplasia-New Considerations for Diagnosis, Management, and Treatment.","authors":"Nadia Merchant, Julie Hoover-Fong, Ricki S Carroll","doi":"10.1210/clinem/dgaf017","DOIUrl":"10.1210/clinem/dgaf017","url":null,"abstract":"<p><p>Achondroplasia is the most common disproportionate short-stature skeletal dysplasia. Features associated with achondroplasia are rhizomelia, macrocephaly, midface hypoplasia, and typical cognition. Potential medical complications include foramen magnum stenosis, hydrocephalus, middle ear dysfunction, obstructive and central sleep apnea, spinal stenosis, and genu varum. Recently, vosoritide, a C-type natriuretic peptide analogue, was approved by the Food and Drug Administration with the primary indication of increasing linear growth in all children with achondroplasia and open growth plates. Due to this, pediatric endocrinologists suddenly are encountering infants and children with achondroplasia in their clinic whose families are seeking treatment with vosoritide. There is an urgent need to provide practical guidance pertaining to the diagnosis, management, and surveillance of these patients. Specific to current clinical use of vosoritide and other growth-modulating therapies in development for patients with achondroplasia, it is important to recognize that 1. some children and their families do not automatically desire such treatment, 2. not all treated children exhibit a response in linear growth, and 3. treatment does not negate the necessity of actively surveilling for the potential complications of achondroplasia that are part of its natural history. The goal of this paper is to provide probable, contemporary clinical scenarios of infants and children with achondroplasia who may present to an endocrinologist. This information is especially crucial to the endocrinologist when there is no specialized skeletal dysplasia center near the family.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2309-e2316"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015384","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":"Detection of SEZ6, a Therapeutic Target, in Medullary Thyroid Carcinoma.","authors":"Bin Xu, Marina K Baine, Achim Jungbluth, Anas Alabkaa, Rene Serrette, Dibisha Roy, Charles M Rudin, Alan L Ho, Eric Sherman, Snjezana Dogan, Ian Ganly, Natasha Rekhtman, Ronald Ghossein","doi":"10.1210/clinem/dgae672","DOIUrl":"10.1210/clinem/dgae672","url":null,"abstract":"<p><strong>Context: </strong>Seizure-related 6 homolog (SEZ6) is a cDNA that is strongly associated with neuroendocrine differentiation. Recently, SEZ6 expression was found in a subset of small cell lung carcinoma (SCLC). Furthermore, ABBV-011, a novel antibody-drug conjugate targeting SEZ6 has been developed and is currently in a clinical trial for the treatment of SCLC and neuroendocrine neoplasms, including medullary thyroid carcinoma (MTC).</p><p><strong>Objective: </strong>We herein present the first evidence that SEZ6 is highly expressed in MTC.</p><p><strong>Methods: </strong>SEZ6 immuno-expression was studied in 78 MTCs and correlated with clinicopathologic characteristics, outcome, and molecular profile.</p><p><strong>Results: </strong>SEZ6 was highly expressed in primary tumors, regional recurrence, and distant metastasis. Using 2 different SEZ6 antibody clones, SC17.14 and 14E5, SEZ6 immunopositivity was seen in 91% to 93% of primary MTCs, 100% of regional recurrence, and 75% to 83% of distant metastasis. High level of SEZ6 immuno-expression determined using H score was associated with male sex, advanced stage, and extrathyroidal thyroidal extension. There was no correlation between SEZ6 expression and outcome or RET/RAS mutation status in MTC. The frequency of SEZ6 positivity in MTC without RET/RAS mutations was 83%.</p><p><strong>Conclusion: </strong>SEZ6 may serve as a novel biomarker for MTCs. Although SEZ6 lacks any prognostic values in MTC, its positivity in 91% to 93% of MTCs, including MTCs without RET and RAS mutations, renders SEZ6-targeted antibody-drug conjugate therapy a promising targeted therapy for MTCs.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2041-2046"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331511","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":"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}

{"title":"Association Between Radius Axial Low-Frequency Ultrasound Velocity and Bone Fragility in Primary Hyperparathyroidism.","authors":"Jessica Pepe, Luciano Colangelo, Daniele Diacinti, Maurizio Angelozzi, Velia Melone, Patrizio Pasqualetti, Marco Occhiuto, Rachele Santori, Salvatore Minisola, Cristiana Cipriani","doi":"10.1210/clinem/dgae695","DOIUrl":"10.1210/clinem/dgae695","url":null,"abstract":"<p><strong>Context: </strong>Radius quantitative ultrasound measurement utilizing portable low-frequency (VLF) axial transmission ultrasound for assessing properties of radius cortical bone revealed a possible role as a screening tool prior to dual-energy x-ray absorptiometry (DXA) to evaluate fragility fracture in some studies.</p><p><strong>Objective: </strong>To evaluate this portable ultrasound device as a screening tool of skeletal fragility in patients with primary hyperparathyroidism (PHPT).</p><p><strong>Methods: </strong>We enrolled 117 postmenopausal women with PHPT. Every subject had a DXA of femur, lumbar spine, nondominant distal one-third radius section, trabecular bone score (TBS) measurement, VLF with a portable device, and spine x-ray.</p><p><strong>Results: </strong>The mean age of the patients was 68 ± 10 years. The measurement of agreement between radius DXA and VLF was: K = 0.43, P < .001. A lower radius ultrasound T-score, also adjusted for years since menopause and body mass index, was associated with DXA-identified osteoporosis at lumbar and/or femoral neck sites: odds ratio (OR) = 1.852 (CI 1.08, 3.18). All fractures were associated with femoral neck T-score: OR = 1.89 (95% CI 1.24, 2.89), as well as with total hip T-score: OR = 1.65 (95% CI 1.09, 2.50), and years since menopause: OR = 1.25 (95% CI 1.02, 1.54).Morphometric vertebral fractures were associated with years since menopause: OR = 1.28 (95% CI 1.02, 1.61), femoral neck T-score OR = 1.96 (95% CI 1.227, 3.135), total hip T-score OR = 1.64 (95% CI 1.04, 2.60), TBS OR = 0.779 (95% CI 0.60-0.99), both ultradistal radius T-score: OR = 1.50 (95% CI 1.05, 2.156), and radius ultrasound T-score: OR = 1.67 (95% CI 1.09, 2.56).</p><p><strong>Conclusion: </strong>VLF could be used for screening purposes prior to DXA to evaluate PHPT fracture risk, only in conditions in which DXA measurement cannot be performed.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1974-1979"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373428","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":"ACTH Stimulation and Oral Salt Loading Tests Detect Biochemical Outcome Early After Primary Aldosteronism Surgery.","authors":"Yuto Ishida, Kazuki Nakai, Kazuki Watanabe, Rei Hirose, Jun Saito, Tetsuo Nishikawa, Yuya Tsurutani","doi":"10.1210/clinem/dgae712","DOIUrl":"10.1210/clinem/dgae712","url":null,"abstract":"<p><strong>Background: </strong>In primary aldosteronism (PA), the biochemical outcomes of the Primary Aldosteronism Surgical Outcome study are used to assess aldosterone hypersecretion 6 to 12 months after surgery. However, few studies have investigated whether the outcomes can be predicted in the early postoperative period. In this retrospective study, we evaluated whether the adrenocorticotropin stimulation test (AST) and oral salt loading test (OST) performed immediately after surgery could predict biochemical outcomes 1 year after surgery.</p><p><strong>Methods: </strong>We assessed 268 patients with PA who underwent adrenalectomy at our hospital between 2008 and 2020, underwent AST and OST within 15 days of surgery, and were assessed for biochemical outcomes 1 year after surgery. Patients were divided into 2 groups: biochemical complete success (B-com; n = 219) and incomplete success (B-inc; n = 49). Patients were divided into clinical complete and partial success and absent success groups. The relationships between various AST and OST values and outcomes were analyzed.</p><p><strong>Results: </strong>The B-inc group had significantly higher plasma aldosterone concentration (PAC) and PAC/serum cortisol ratio (PAC/Cort) at baseline and after ACTH loading in AST and 24-hour urine aldosterone in OST than the B-com group. PAC/Cort at 30 minutes after ACTH loading [area under the curve (AUC) = 0.76] and 24-hour urine aldosterone (AUC = 0.77) were relatively superior predictors of the outcome. Parameters after ACTH loading were better predictors of biochemical and clinical outcomes than baseline.</p><p><strong>Conclusion: </strong>AST and OST immediately after surgery can predict biochemical and clinical outcomes 1 year after surgery in patients with PA.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1938-1945"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394875","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":"The Maturity-Onset Diabetes of the Young (MODY) Calculator Overestimates MODY Probability in Hispanic Youth.","authors":"Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur","doi":"10.1210/clinem/dgae770","DOIUrl":"10.1210/clinem/dgae770","url":null,"abstract":"<p><strong>Context: </strong>The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.</p><p><strong>Objective: </strong>We aimed to test its real-world application in Hispanic youth.</p><p><strong>Methods: </strong>We conducted a retrospective chart review of Hispanic youth (<23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).</p><p><strong>Results: </strong>Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an expected 382 individuals with MODY, which is much higher than previous estimations (1-5%; ie, 20-102 individuals in this cohort). A total of 18 individuals tested positive for MODY among the limited number of individuals tested based on clinical suspicion and genetic testing availability (n = 44 out of 2033 tested, 2.2% of overall cohort).</p><p><strong>Conclusion: </strong>The MODY risk calculator likely overestimates the probability of MODY in Hispanic youth, largely driven by an overestimation in those not early-insulin treated (predominantly young-onset type 2 diabetes). The calculator needs updating to improve its applicability in this population. In addition, further research is needed to help better identify MODY in Hispanic youth.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2191-e2197"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570062","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":"Implementation Strategies for Inpatient Continuous Glucose Monitoring-based Diabetes Management: A Systematic Review.","authors":"Mikkel T Olsen, Alexandros L Liarakos, Emma G Wilmot, Ketan Dhatariya, Hood Thabit, David Sánchez-García, Kirsten Nørgaard, Ulrik Pedersen-Bjergaard, Katrine B Hansen, Roman Vangoitsenhoven, Chantal Mathieu, Peter L Kristensen, Julia K Mader","doi":"10.1210/clinem/dgaf074","DOIUrl":"10.1210/clinem/dgaf074","url":null,"abstract":"<p><strong>Introduction: </strong>Continuous glucose monitoring (CGM) provides real-time glucose data that has revolutionized outpatient diabetes care; however, its impact on inpatient care remains limited, likely due to the lack of standardized CGM-based insulin titration protocols, implementation strategies, and proper familiarity with the technology, among others.</p><p><strong>Methods: </strong>A systematic literature search was conducted on October 15, 2024, using PubMed and Embase, without a restriction on publication date. The search focused on CGM-based insulin titration protocols and related implementation strategies in non-intensive care unit (non-ICU) settings. This systematic review was registered with PROSPERO (RD42024596819).</p><p><strong>Results: </strong>A total of 7625 references were screened. Nine protocols for inpatient CGM-based insulin titration and related implementation strategies were identified. Six protocols recommended a weight-based basal-bolus insulin regimen. Insulin titration on basal and bolus insulin was mostly done daily based on either clinical discretion or clearly defined insulin titration protocols. All protocols employed a hybrid approach, utilizing both CGM and finger prick glucose testing to guide glucose management. Diabetes-trained staff oversaw CGM-based insulin titration and glucose management in 5 protocols. CGM alarm settings varied widely, with hyperglycemic alarm thresholds between >13.9 and >22.2 mmol/L and hypoglycemia alarm thresholds between <3.9 and <5.0 mmol/L.</p><p><strong>Conclusion: </strong>We observed considerable variation in the detail and clarity provided by the reviewed protocols. This highlights the need for standardized operational protocols for CGM-based insulin titration and related implementation strategies to implement CGM effectively in non-ICU settings.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2411-e2419"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366734","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":"Testosterone and Male Bone Health: A Puzzle of Interactions.","authors":"Marta Tenuta, Valeria Hasenmajer, Daniele Gianfrilli, Andrea M Isidori","doi":"10.1210/clinem/dgaf191","DOIUrl":"10.1210/clinem/dgaf191","url":null,"abstract":"<p><p>Sex steroids are pivotal in skeletal development and maintenance throughout life. Testosterone primarily drives male cortical bone growth and periosteal expansion, particularly during puberty, while estradiol (E2) is essential for trabecular bone formation and inhibiting resorption. The conversion of testosterone to dihydrotestosterone and E2, the transport proteins, the somatotropic axis, and the nonandrogenic functions of the testis underscore the intricate interplay protecting male bone health. Clinical models, including estrogen resistance, aromatase deficiency, and complete androgen insensitivity syndromes, highlight E2's critical role in maintaining male bone integrity. The use of aromatase inhibitors and androgen deprivation therapy reveals the adverse effects of estrogen and androgen blockade, often resulting in substantial bone loss. Gender-affirming hormone therapies provide further insights into testosterone's influence on cortical bone during development and the maintenance role of sex steroids in adulthood. This review digs into the link between male hypogonadism and osteoporosis, emphasizing testosterone replacement therapy (TRT) and findings from major trials, including T-Trial Bone, T4Bone, and TRAVERSE Fracture. While TRT has been shown to improve bone mineral density, its effect on fracture risk remains inconclusive. Unexpected findings from the TRAVERSE Fracture trial highlight the importance of caution and confirm that antiresorptive therapies remain the first-line treatment for male osteoporosis. Investigating the synergistic effects of combining TRT with antiresorptive therapies, the effect of therapeutic timing on peak bone mass accrual, and the role of confounders in fracture risk are promising areas for future research to optimize male skeletal health.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2121-e2135"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694308","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":"Dose-Specific Effects of Denosumab on Serum Calcium Levels in Patients With Osteoporosis and Various Renal Functions.","authors":"Xiaoxu Sun, Marcy B Bolster, Benjamin Z Leder, WuQiang Fan","doi":"10.1210/clinem/dgae721","DOIUrl":"10.1210/clinem/dgae721","url":null,"abstract":"<p><strong>Context: </strong>Patients with osteoporosis and advanced chronic kidney disease (CKD) are at increased risk for hypocalcemia when initiating denosumab. It remains unclear if subsequent doses of denosumab pose a similar hypocalcemia risk as the initial dose.</p><p><strong>Objectives: </strong>To study dose-specific hypocalcemia risks of denosumab.</p><p><strong>Design, setting, patients, and exposure: </strong>An observational study of 10 398 consecutive patients with varying renal function who received denosumab within the Mass General Brigham healthcare system between January 1, 2016, and February 29, 2024.</p><p><strong>Main outcomes and measures: </strong>Dose-specific effects of denosumab on serum calcium levels and incidence of hypocalcemia (albumin-corrected serum calcium level < 8.5 mg/dL).</p><p><strong>Results: </strong>In 159 patients with sufficient data for 3 consecutive doses of denosumab, the initial dose of denosumab reduced serum calcium levels by an average of 0.34, 0.52, and 1.12 mg/dL in patients with glomerular filtration rate (GFR) of ≥60 (n = 89), 30 to 59 (n = 46), and < 30 (n = 24) mL/min/1.73m2, respectively (P < .001). Among patients with GFR of < 30 mL/min/1.73m2, the initial, second, and third dose of denosumab reduced serum calcium levels by an average of 1.12, 0.72, and 0.60 mg/dL, respectively (P = .014). In a cohort of 325 patients with sufficient data for 2 doses of denosumab, a Kaplan-Meier analysis revealed a trend of higher incidence of hypocalcemia following the initial dose compared to the second dose in patients with GFR of < 30 mL/min/1.73m2.</p><p><strong>Conclusion: </strong>The magnitude of serum calcium decrease following subsequent dose(s) was smaller than that following the initial dose of denosumab among patients with osteoporosis and advanced CKD.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1915-1922"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401717","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}