Effects of low-dose hydrochlorothiazide on urolithiasis and bone metabolism in severely disabled individuals: A pilot study

To clarify the effects of hydrochlorothiazide (HCT) on calcium metabolism in subjects with severe motor and intellectual disabilities (SMID), we examined four patients (16-48 years old) with a history of urolithiasis and/or bone fracture and increased urinary calcium/creatinine ratio (U-Ca/Cr). U-Ca/Cr, blood markers of bone turnover, and bone-mineral density (BMD) were measured before and after administration of low-dose HCT (0.25-0.5 mg/kg/day). Three months after the initiation of HCT, U-Ca/Cr decreased in all patients, but this effect was less evident at 9-18 months. Bone-turnover marker of bone-specific alkaline phosphatase also showed a tendency to decrease, but BMD remained unchanged during the follow-up period. In SMID patients, HCT is beneficial for the treatment of hypercalciuria but its effects can be transient in certain cases. HCT may also ameliorate the increase in bone turnover, but its effects on the prevention of bone fractures remain uncertain. Hyponatremia is the most frequent and significant adverse effect of HCT, for which a close observation is mandatory in HCT application for patients with SMID.