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Abstract: SA-PO305

Effect of Hydrochlorothiazide on Bone Mineral Density in Patients with Kidney Stones: A Post Hoc Analysis of the NOSTONE Trial

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Bargagli, Matteo, Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Drakopoulos, Dionysios, Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Primetis, Elias, Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Cereghetti, Grazia Maria, Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Roth, Beat, Department of Urology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
  • Bonny, Olivier, Service of Nephrology, Department of Medicine, Fribourg State Hospital and University of Fribourg, Fribourg, Switzerland
  • Fuster, Daniel G., Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Background

Low bone mass and fractures are highly prevalent in patients with kidney stones. Thiazide diuretics lower urine calcium and hence may preserve bone mass. No placebo-controlled randomized trial (RCT) has been conducted to examine the impact of thiazide diuretics on bone mineral density (BMD) in patients with kidney stones.

Methods

We conducted a post-hoc analysis of the NOSTONE trial to assess a range of hydrochlorothiazide (HCT) doses or placebo on bone mineral density in patients with recurrent calcium-containing kidney stones. Computed tomography (CT) attenuation was measured at T12-L3 vertebrae in Hounsfield units (HU) at baseline and the end of the study, using a previously validated approach, with lower values corresponding to lower BMD. BMD measurements were performed by two independent readers blinded to the study intervention. Random-effects linear regression models were used to investigate treatment effects on changes from baseline.

Results

BMD measurements were available in 388 of 416 (93%) randomized patients. Median follow-up time was 2.92 years. At baseline, mean BMD was directly associated with eGFR (β 0.934 HU, 95% confidence interval [CI] 0.680; 1.189, p < 0.001) and inversely with age (β -2.208 HU, 95% CI -2.510; -1.907, p < 0.001). Mean BMD decreased by 6.4±15.7 HU in the placebo group, by 5.1±15.1 in the 12.5mg HCT group (β coefficient vs placebo, 0.368 HU, 95% CI -1.735; 2.472, p = 0.732), by 4.1±16.3 in the 25mg HCT group (β 0.926 HU, 95% CI -1.335; 3.187, p = 0.422), and by 4.8±15.9 in the 50mg HCT group (β 0.699 HU, 95% CI -1.450; 2.848, p = 0.524). No association was observed between HCT dose and change in BMD (p = 0.430). The results were confirmed in sensitivity analyses for eGFR, urinary calcium, body mass index, and in per-protocol analyses.

Conclusion

In patients with recurrent calcium-containing kidney stones, loss of bone mineral density was similar in patients receiving hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily.