Endocrine Abstracts

JOINT1934

Introduction: Idiopathic hypercalciuria (IH) - defined by 24 hours urinary calcium levels (CaUr24h/kg) >4 mg/kg - is a cause of secondary osteoporosis, affecting 30% of postmenopausal women. IH is thought to lead to a compensatory increase of bone turnover and, thus, to a bone loss. The reduction of hypercalciuria is achieved through low-dose thiazide diuretics (hydrochlorothiazide, HCT), whose effect on skeletal turnover is unknown. This study evaluates the effect of HCT on bone turnover in postmenopausal osteoporotic women.

Materials and Methods: 82 postmenopausal women with a median age of 59 years (interquartile range 55-66), affected by osteoporosis and IH were retrospectively enrolled from a multicenter case series. All patients had normal calcium intake (by diet and/or supplements), were supplemented with cholecalciferol and were not taking antiresorptive medications. Patients with secondary hypercalciuria (i. e., primary hyperparathyroidism, endogenous or exogenous hypercortisolism) were excluded. At enrollment (T0), calcium, phosphate, 25OH-vitamin D, parathyroid hormone (PTH), C-terminal telopeptide (CTX), alkaline phosphatase (ALP), CaUr24h/kg, and creatinine clearance (ClCr) were measured; 6-12 months (T1) and 18-24 months (T2, n = 48) after the initiation of a treatment with HCT (12. 5 mg or 25 mg/day), the same parameters were reassessed. Normalization of CaUr24h/kg and reduction of CTX were considered as primary outcomes.

Results: A normalization of calciuria was observed in 43. 9% patients (36/82) at T1 and in 60. 4% (29/48) at T2. Moreover, the paired data obtained from the patients were analyzed longitudinally, showing a significant reduction at T1 and T2 compared to T0 in both CaUr24h/kg values (-1. 26±0. 19 mg/kg/24h, P < 0. 001; -1. 23±0. 25 mg/kg/24h, P < 0. 001) and CTX values (-140±32 ng/ml, P < 0. 001; -90±29 ng/ml, P < 0. 005). No significant differences were observed in CaUr24h/kg values (0. 03±0. 24 mg/kg/24h, P = 0. 91) between T1 and T2, while a slight increase in CTX values was noted (49±22 ng/ml, P = 0. 031). A slight increase in calcium levels was observed between T0 and T1 (0. 17±0. 06 mg/dl, P < 0. 005) and T0 and T2 (0. 13±0. 07 mg/dl, P = 0. 08), although not statistically significant, but not between T1 and T2 (-0. 04±0. 07 mg/dl, P = 0. 52). No significant differences were found in the levels of phosphate, 25OH-vitamin D, PTH, ALP, or renal function among T0, T1, and T2.

Conclusion: the use of HCT in osteoporosis secondary to idiopathic hypercalciuria in postmenopausal women appears to reduce the bone resorption process. However, the sample size, the short duration and the design of the study do not allow for conclusive information on the persistent effects on turnover, bone mineral density, and fracture risk.