BACKGROUND: Low bone mass and fractures are common among kidney stone formers, yet it remains unclear whether thiazides can help preserve bone mass. We aimed to evaluate the effectiveness of a range of hydrochlorothiazide (HCTZ) doses compared to a placebo on bone mineral density (BMD) over a three-year period. METHODS: This post-hoc analysis was conducted on data from the NOSTONE trial, a multicenter, randomized, controlled study. A total of 416 adults with recurrent calcium stones participated in the study, receiving either placebo or HCTZ at doses of 12.5 mg, 25 mg or 50 mg daily. BMD was measured using computed tomography (CT) at the T12-L3 vertebrae both at baseline and the end of the study. RESULTS: Over a median follow-up period of 2.92 years, the mean BMD decreased by 6.4±15.7 Hounsfield Units (HU) in the placebo group, 5.1±15.1 HU in the 12.5 mg HCTZ group (β coefficient vs placebo, 0.37 HU, 95% CI -1.74
2.47, p = 0.73), 4.1±16.3 HU in the 25 mg HCTZ group (β 0.93 HU, 95% CI -1.34
3.19, p = 0.42), and 4.8±15.9 HU in the 50 mg HCTZ group (β 0.70 HU, 95% CI -1.45
2.85, p = 0.52). No association was observed between HCT dose and BMD at the end of the study (p = 0.43). The results were confirmed in sensitivity analyses for eGFR, urine calcium, net gastrointestinal alkali absorption, body mass index (BMI), in subgroup and in per-protocol analyses. CONCLUSIONS: In patients with recurrent calcium kidney stones, loss of BMD was similar in patients receiving HCTZ at a dose of 12.5 mg, 25 mg, or 50 mg, or placebo once daily.