Hydrochlorothiazide with salt restriction in nonsurgical hypoparathyroidism: a placebo-controlled single-blinded randomized crossover trial assessing efficacy and safety

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Publicat a:JBMR Plus vol. 9, no. 12 (Dec 2025)
Autor principal: Jha, Vivek
Altres autors: Mukherjee, Soham, Bhadada, Sanjay Kumar, Sahni, Nancy, Ram, Sant, Dutta, Pinaki
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Oxford University Press
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022 |a 2473-4039 
024 7 |a 10.1093/jbmrpl/ziaf174  |2 doi 
035 |a 3274967253 
045 2 |b d20251201  |b d20251231 
100 1 |a Jha, Vivek  |u Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
245 1 |a Hydrochlorothiazide with salt restriction in nonsurgical hypoparathyroidism: a placebo-controlled single-blinded randomized crossover trial assessing efficacy and safety 
260 |b Oxford University Press  |c Dec 2025 
513 |a Journal Article 
520 3 |a In this single-center, randomized, placebo-controlled, single-blinded, crossover trial (Clinical Trial Registry-India: CTRI/2024/08/090041), we evaluated the efficacy and safety of low-dose hydrochlorothiazide (HCTZ) in adults with nonsurgical hypoparathyroidism (excluding autoimmune and obvious syndromic forms). After stabilization on fixed doses of calcium carbonate and calcitriol under a controlled low-sodium diet, 26 participants received HCTZ (12.5-25&#xa0;mg/d) or placebo for 7&#xa0;d, with a 15-d washout before crossover, followed by an optional 4-wk open-label HCTZ extension. The primary outcome was change in serum calcium; secondary outcomes included change in 24-h urinary calcium (UCa), fractional calcium excretion, urinary sodium, and bone turnover markers (β-CTX and P1NP). Compared to baseline (8.61 ± 0.32&#xa0;mg/dL), serum calcium increased significantly with HCTZ at day 5 (9.01 ± 0.46&#xa0;mg/dL) and day 8 (9.04 ± 0.52&#xa0;mg/dL; p < .001), while no significant change occurred with placebo. Hydrochlorothiazide reduced 24-h UCa by −26.3% at day 8 (vs +4.7% with placebo; p < .001). These effects remained robust in sensitivity analyses adjusting for urinary sodium and when expressed per kg body weight. Fractional calcium excretion fell by 29.9% with HCTZ (p < .001). A small but statistically significant decline in serum potassium was observed at day 8 (from 4.18 to 3.95&#xa0;mEq/L; p < .001), though values remained within the normal range, no participants developed hypokalemia; renal function and intact PTH (iPTH) were stable. During the extension phase, serum calcium levels rose while UCa excretion declined significantly, without any reported adverse effects. These findings indicate that low-dose HCTZ with sodium restriction safely improves calcium homeostasis in nonsurgical hypoparathyroidism—raising serum calcium and reducing calciuria—with good tolerability. Hydrochlorothiazide offers a cost-effective adjunct to standard therapy and warrants further investigation for long-term outcomes.Lay Summary In 26 adults with nonsurgical hypoparathyroidism, low-dose hydrochlorothiazide (12.5-25&#xa0;mg daily) raised serum calcium levels and reduced calcium loss in urine within 1&#xa0;wk, without causing harmful side effects. A 4-wk extension confirmed sustained benefits. This simple, safe, and affordable treatment may improve calcium control alongside standard therapy and may reduce kidney-related complications. 
653 |a Clinical trials 
653 |a Nutrient deficiency 
653 |a Bone turnover 
653 |a Parathyroid hormone 
653 |a Sodium 
653 |a Collagen 
653 |a Placebos 
653 |a Sensitivity analysis 
653 |a Renal function 
653 |a Calciuria 
653 |a Hydrochlorothiazide 
653 |a Hypokalemia 
653 |a Calcium carbonate 
653 |a Excretion 
653 |a Homeostasis 
653 |a Statistical analysis 
653 |a Calcium (blood) 
653 |a Hypoparathyroidism 
653 |a Calcium (urinary) 
653 |a Body weight 
653 |a Calcium homeostasis 
653 |a Calcitriol 
700 1 |a Mukherjee, Soham  |u Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
700 1 |a Bhadada, Sanjay Kumar  |u Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
700 1 |a Sahni, Nancy  |u Department of Dietetics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
700 1 |a Ram, Sant  |u Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
700 1 |a Dutta, Pinaki  |u Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India 
773 0 |t JBMR Plus  |g vol. 9, no. 12 (Dec 2025) 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3274967253/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3274967253/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch