Endocrine Abstracts

Hypercalciuria may represent a challenge during the workup for osteoporosis management. The present study aimed: 1) to describe the phenotype associated with hypercalciuria in vitamin D-repleted (serum 25OHD > 20 ng/ml) osteopenic/osteoporotic patients, focusing on kidney, bone and mineral metabolic features; 2) to analyze the effects of thiazides and anti-resorptive drugs on urine calcium excretion (UCa) and mineral metabolism markers. Seventy patients (67 postmenopausal females; mean ± sd age 63.5 ± 7.8 years) with hypercalciuria (UCa > 4.0 mg/kg body weight/24 h on two determinations) were retrospectively enrolled in a real-world setting. Median (interquartile range) UCa was 5.25 (4.60–6.50) mg/kg/24 h. Kidney stones occurred anamnestically/by imaging in 28% of patients, whose UCa was similar to that of patients without kidney stones [5.2 (4.4, 6.7) vs 5.2 (4.6, 6.5) mg/kg/24 h]. By means of bone densitometry scan (n = 66), osteoporosis was diagnosed in 65% of patients at lumbar site and in 45% at femour site; 50% of patients experienced at least one fragility fracture. Clustering analysis considering the 3 correlated variables serum calcium, phosphate and PTH, identified 3 clusters of hypercalciuric patients: cluster 1 (n = 27) included patients with normal mineral profile, cluster 2 (n = 33) included patients with relatively elevated PTH, normocalcemia and normophosphatemia, resembling normocalcemic hyperparathyroidism, while cluster 3 (n = 10) included patients with a primary hyperparathyroidism-like profile, suggesting a certain degree of autonomous PTH secretion from parathyroid glands. After a follow up of 2.2 ± 1.3 years, 56 patients were reevaluated; 40 patients were treated with thiazides (13 with hydrochlorothiazide, 27 with indapamide). Concomitant therapies were: bisphophonates (n = 12), denosumab (n = 14), calcium salts (n = 15). Thiazides induced a mean 41% reduction in UCa and 64% of patients obtained UCa < 4.0 mg/kg/24 h. Hydrochlorothiazide and indapamide reduced UCa at a similar extent (−2.3 ± 0.9 vs −2.6 ± 1.2 mg/kg/24 h). Multiple logistic regression analysis showed that: 1) thiazides induced a consistent UCa reduction (r² = 0.330), though the effect did not reach significance (P = 0.08), while bisphosphonates and denosumab did not affect UCa; 2) increases in PTH levels were induced by bisphosphonates (P = 0.02) and denosumab (P = 0.02), but not by hypercalciuria, but the effects were limited (r² = 0.059); 3) similarly, reduction in calcium levels were induced by bisphosphonates (P = 0.02) and denosumab (P = 0.01), but not by hyperecalciuria, with clinically inconsistent effects (r² = 0.04 and r² = 0.08, respectively). In conclusion, in elder osteoporotic patients, hypercalciuria is associated with kidney stones in about one fourth of patients and with a wide range of impaired PTH secretion. Thiazides normalized urine calcium excretion in about 2/3 of patients.