Hypercalciuria in Postmenopausal Women With Reduced Bone Mineral Density Is Associated With Different Mineral Metabolic Profiles: Effects of Treatment With Thiazides and Anti-resorptives

Abstract

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-sufficient (serum 25 hydroxyvitamin D (25OHD) > 20 ng/ml) patients with osteopenia/osteoporosis; (2) to analyze the effects of thiazides and anti-resorptive drugs on urine calcium excretion (UCa), mineral metabolic markers, and bone mineral density. Seventy-seven postmenopausal women with hypercalciuria (Uca > 4.0 mg/kg body weight/24 h on two determinations) were retrospectively evaluated in a real-life setting. Median UCa was 5.39 (4.75–6.70) mg/kg/24 h. Kidney stones occurred in 32.9% of patients, who had median UCa similar to that of patients without kidney stones. Clustering analysis considering the three variables, such as serum calcium, phosphate, and parathormone (PTH), identified two main clusters of hypercalciuric patients. Cluster 1 (n = 13) included patients with a primary hyperparathyroidism-like profile, suggesting a certain degree of autonomous PTH secretion from parathyroid glands. Within cluster 2 (n = 61), two subgroups were recognized, cluster 2A (n = 18) that included patients with relatively increased PTH and normophosphatemia, and cluster 2B (n = 43) that included patients with the normal mineral profile. After a follow-up of 33.4 ± 19.6 months, 49 patients treated with thiazidic diuretics (TZD) were reevaluated; 20 patients were treated with hydrochlorothiazide (HCT; 12.5–37.5 mg/day), 29 with indapamide (IND; 1.50–3.75 mg/day). Any significant difference could be detected in all the parameters both basal and treated conditions between patients treated with HCT or IND. TZD induced a mean 39% reduction in UCa and 63.3% of patients obtained Uca < 4.0 mg/kg/24 h, independent of their mineral metabolic profile. Moreover, TZD induced a significant decrease in PTH levels. TZD-treated patients normalizing UCa experienced an increase in bone mineral densities when concomitantly treated with anti-resorptives, while any gain could be observed in TZD-treated patients with persistent hypercalciuria. Finally, multiple regression analysis showed that UCa reduction was at least in part related to denosumab treatment. In conclusion, in postmenopausal osteoporotic women, hypercalciuria is associated with kidney stones in about one-third of patients and with a wide range of impaired PTH secretion, determining a diagnostic challenge. TZD efficiently reduces UCa and normalization contributes to increasing anti-resorptives positive effect on bone mineral density.

The Optimal Length of Pharmacological Prophylaxis in Calcium Kidney Stone Formers

“…15 Both alteration in bone metabolism (whether as a primary condition or as a response to the buffering of the acid load) and direct tubular calcium leak generated by dietary proteins likely play pivotal roles in increased calciuria and lithogenesis. 22 Such patients with stone benefit from drugs typically used for preventing stones (thiazides, citrate) because they are effective on both bone turnover [23][24][25] and agents generally used for the treatment of osteoporosis, some of which (e.g., bisphosphonates) are known to reduce calciuria 26 and stone occurrence. 27 Stratification of stone formers according to osteoporosis/ osteopenia risk, depending on the existence of one or more conditions, such as medullary sponge kidney, distal renal tubular acidosis, primary hyperparathyroidism, malabsorptive syndromes and fasting hypercalciuria, and/or the results of bone densitometry, may help when opting for long-term treatment of stone-forming patients.…”

“… 15 Both alteration in bone metabolism (whether as a primary condition or as a response to the buffering of the acid load) and direct tubular calcium leak generated by dietary proteins likely play pivotal roles in increased calciuria and lithogenesis. 22 Such patients with stone benefit from drugs typically used for preventing stones (thiazides, citrate) because they are effective on both bone turnover 23 – 25 and agents generally used for the treatment of osteoporosis, some of which ( e.g. , bisphosphonates) are known to reduce calciuria 26 and stone occurrence.…”

Community pharmacy is the key to improving vitamin D levels

“… 11 There are also a multitude of drugs that interfere with the absorption and/or metabolism of vitamin D; the most characteristic are carbamazepine, cimetidine, cholestyramine, colestipol, thiazide diuretics, phenytoin, phenobarbital and valproate. 12 , 13 , 14 , 15 , 16 …”

Associations between lumbar bone mineral density, serum 25-hydroxyvitamin D and history of kidney stones in adults aged 30–69 years in the USA (NHANES 2011–2018)

“…Therefore, we aimed to determine the relationship between a history of kidney stones and human bone health. As many patients with kidney stones have hypercalciuria, clinicians are concerned that their bone mineral density (BMD) may be reduced, which has inspired several recent studies 5–8. Although many studies have found that the occurrence of kidney stones is associated with a decreased BMD, the results remain inconclusive.…”