{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T21:33:37Z","timestamp":1781904817870,"version":"3.54.5"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>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) &amp;gt; 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 &amp;gt; 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\u20136.70) 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 (<jats:italic>n<\/jats:italic> = 13) included patients with a primary hyperparathyroidism-like profile, suggesting a certain degree of autonomous PTH secretion from parathyroid glands. Within cluster 2 (<jats:italic>n<\/jats:italic> = 61), two subgroups were recognized, cluster 2A (<jats:italic>n<\/jats:italic> = 18) that included patients with relatively increased PTH and normophosphatemia, and cluster 2B (<jats:italic>n<\/jats:italic> = 43) that included patients with the normal mineral profile. After a follow-up of 33.4 \u00b1 19.6 months, 49 patients treated with thiazidic diuretics (TZD) were reevaluated; 20 patients were treated with hydrochlorothiazide (HCT; 12.5\u201337.5 mg\/day), 29 with indapamide (IND; 1.50\u20133.75 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 &amp;lt; 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.<\/jats:p>","DOI":"10.3389\/fmed.2021.780087","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T10:11:27Z","timestamp":1639563087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypercalciuria in Postmenopausal Women With Reduced Bone Mineral Density Is Associated With Different Mineral Metabolic Profiles: Effects of Treatment With Thiazides and Anti-resorptives"],"prefix":"10.3389","volume":"8","author":[{"given":"Federico","family":"Nicoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Dito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Guabello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Longhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Corbetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.3390\/nu10030366","article-title":"Vitamin D, hypercalciuria and kidney stones","volume":"10","author":"Letavernier","year":"2018","journal-title":"Nutrients."},{"key":"B2","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s40618-019-01162-y","article-title":"Hypercalciuria: its value as a predictive risk factor for nephrolithiasis in asymptomatic primary hyperparathyroidism?","volume":"43","author":"Saponaro","year":"2020","journal-title":"J Endocrinol Invest."},{"key":"B3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1530\/EJE-13-0102","article-title":"Prevalence of subclinical contributors to low bone mineral density and\/or fragility fracture","volume":"169","author":"Eller-Vainicher","year":"2013","journal-title":"Eur J Endocrinol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1159\/000369833","article-title":"Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies","volume":"40","author":"Arcidiacono","year":"2014","journal-title":"Am J Nephrol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"563","DOI":"10.2174\/1568009615666150602143041","article-title":"Molecular and clinical aspects of the target therapy with the calcimimetic cinacalcet in the treatment of parathyroid tumors","volume":"15","author":"Mingione","year":"2015","journal-title":"Curr Cancer Drug Targets."},{"key":"B6","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00240-018-1096-0","article-title":"Calcium-sensing receptor: evidence and hypothesis for its role in nephrolithiasis","volume":"47","author":"Vezzoli","year":"2019","journal-title":"Urolithiasis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s00424-018-2184-2","article-title":"Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy","volume":"471","author":"Bergwitz","year":"2019","journal-title":"Pflugers Arch."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1210\/clinem\/dgaa217","article-title":"Digenic heterozygous mutations in SLC34A3 and SLC34A1 cause dominant hypophosphatemic rickets with hypercalciuria","volume":"105","author":"Gordon","year":"2020","journal-title":"J Clin Endocrinol Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1097\/MNH.0000000000000239","article-title":"Claudins and mineral metabolism","volume":"25","author":"Hou","year":"2016","journal-title":"Curr Opin Nephrol Hypertens."},{"key":"B10","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1007\/s11914-012-0120-5","article-title":"Idiopatic hypercalciuria and bone health","volume":"10","author":"Ryan","year":"2012","journal-title":"Curr Osteoporos Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.beem.2018.09.001","article-title":"Classical complications of primary hyperparathyroidism","volume":"32","author":"Minisola","year":"2018","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1210\/jc.2014-4548","article-title":"Hypercalciuria may persist after successful parathyroid surgery and it is associated with parathyroid hyperplasia","volume":"100","author":"Palmieri","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40618-015-0261-3","article-title":"Italian society of endocrinology consensus statement: definition, evaluation and management of patients with mild primary hyperparathyroidism","volume":"38","author":"Marcocci","year":"2015","journal-title":"J Endocrinol Invest."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1172\/JCI24134","article-title":"Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia","volume":"115","author":"Nijenhuis","year":"2005","journal-title":"J Clin Invest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12967-020-02270-7","article-title":"Use of thiazide diuretics for the prevention of recurrent kidney calculi: a systematic review and meta-analysis","volume":"18","author":"Li","year":"2020","journal-title":"J Transl Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.17458\/per.vol15.2018","article-title":"The effects of diuretics on mineral and bone metabolism","volume":"15","author":"Alon","year":"2018","journal-title":"Pediatr Endocrinol Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1053\/j.ajkd.2013.12.006","article-title":"GFR estimation: from physiology to public health","volume":"63","author":"Levey","year":"2014","journal-title":"Am J Kidney Dis."},{"key":"B18","volume-title":"PAST: Paleontological Statistics Software Package For Education","author":"Hammer","year":"2001"},{"key":"B19","doi-asserted-by":"publisher","first-page":"546","DOI":"10.3390\/nu10050546","article-title":"Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) position statement: clinical management of vitamin D deficiency in adults","volume":"10","author":"Cesareo","year":"2018","journal-title":"Nutrients."},{"key":"B20","first-page":"1522","article-title":"Diet therapy and life guidance to prevent calcium stones","volume":"21","author":"Moriyama","year":"2011","journal-title":"Clin Calcium."},{"key":"B21","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/BF03345354","article-title":"Risk factors associated to kidney stones in primary hyperparathyroidism","volume":"28","author":"Corbetta","year":"2005","journal-title":"J Endocrinol Invest."},{"key":"B22","doi-asserted-by":"publisher","first-page":"R39","DOI":"10.1530\/EJE-16-0430","article-title":"MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects","volume":"176","author":"Verdelli","year":"2017","journal-title":"Eur J Endocrinol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"dgaa233","DOI":"10.1210\/clinem\/dgaa233","article-title":"Hypomagnesuria is associated with nephrolithiasis in patients with asymptomatic primary hyperparathyroidism","volume":"105","author":"Saponaro","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1089\/end.2008.0567","article-title":"Differentiating primary from secondary hyperparathyroidism in stone patients: the \u201cthiazide challenge\u201d","volume":"23","author":"Eisner","year":"2009","journal-title":"J Endourol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.780087\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T10:11:34Z","timestamp":1639563094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.780087\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,15]]},"references-count":24,"alternative-id":["10.3389\/fmed.2021.780087"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.780087","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,15]]},"article-number":"780087"}}