{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:46:06Z","timestamp":1782794766253,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>While aldosterone\u2019s detrimental role in osteoporosis through activation of the mineralocorticoid receptor (MR) and its downstream target SGK1 is recognized, it remains unclear whether bone itself can reciprocally regulate systemic aldosterone metabolism. Inspired by the traditional Chinese medicine theory of \u201cKidney Governing the Bones,\u201d this study investigated the hypothesis of a bidirectional \u201cbone-kidney\u201d axis, examining whether anti-osteoporosis treatments could systemically modulate the aldosterone-MR\/SGK1 axis while improving bone mass. Using an orchiectomized (ORX) aging male rat model, we intervened with either the flavonoid naringin (200 mg\/kg\/d, gavage) or the anti-RANKL antibody denosumab (6.3 mg\/kg, s.c.). Micro-CT analysis confirmed that naringin significantly increased bone mineral density (BMD) and improved trabecular microarchitecture, with a similar exploratory trend in the denosumab group (e.g., increased bone volume fraction (BV\/TV) and trabecular number (Tb.N), decreased trabecular separation (Tb.Sp)). Notably, ELISA revealed that the ORX-induced elevation in serum aldosterone was markedly suppressed by both naringin and denosumab. At the molecular level, qPCR and Western blot analyses demonstrated that both treatments inhibited the upregulated MR\/SGK1 signaling pathway in the kidney and suppressed MR expression in bone tissue, concurrently correcting the imbalance in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)\/Runt-related transcription factor 2 (Runx2) expression in femur. This study provides the first experimental evidence that bone- targeted interventions can downregulate systemic aldosterone levels and its key signaling pathway, suggesting a functional bone- kidney crosstalk that warrants further mechanistic investigation.<\/jats:p>","DOI":"10.3389\/fendo.2026.1794408","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:24:15Z","timestamp":1782793455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Naringin and denosumab ameliorate osteoporosis and suppress the aldosterone-MR\/SGK1 signaling axis by modulating the bone-kidney interorgan communication in Orchiectomized rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Shishuo","family":"Xiong","sequence":"first","affiliation":[{"name":"The Third Clinical Medical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, 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