{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:00:41Z","timestamp":1791907241180,"version":"4.3.4"},"reference-count":174,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Tzu-Chi Hospital, Taiwan","award":["TCRD-TPE-115-46"],"award-info":[{"award-number":["TCRD-TPE-115-46"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and microarchitectural deterioration, leading to increased fracture risk, particularly in aging populations. Postmenopausal osteoporosis (PMOP) remains the most common primary form and results from abrupt estrogen deficiency after menopause, which disrupts bone remodeling by accelerating the receptor activator of nuclear factor-\u03baB ligand (RANKL)-mediated osteoclastogenesis, suppressing Wnt\/\u03b2-catenin signaling, and promoting inflammatory cytokine production. In contrast, drug-induced osteoporosis (DIOP) encompasses a heterogeneous group of secondary bone disorders arising from pharmacologic exposures. Glucocorticoids suppress osteoblastogenesis, enhance osteoclast activity, and increase reactive oxygen species; long-term bisphosphonate therapy may oversuppress bone turnover, resulting in microdamage accumulation; denosumab withdrawal triggers a unique rebound surge in RANKL activity, often leading to rapid bone loss and multiple vertebral fractures. Medications including aromatase inhibitors, SSRIs, proton pump inhibitors, heparin, and antiepileptic drugs impair bone quality through diverse mechanisms. Standard antiresorptive agents remain first-line therapies, while anabolic agents such as teriparatide, abaloparatide, and romosozumab provide enhanced benefits in high-risk or drug-suppressed bone states. Transitional bisphosphonate therapy is essential when discontinuing denosumab, and individualized treatment plans\u2014including drug holidays, lifestyle interventions, and monitoring vulnerable patients\u2014are critical for optimizing outcomes. Emerging approaches such as small interfering RNA (siRNA)-based therapeutics, anti-sclerostin agents, digital monitoring technologies, and regenerative strategies show promise for future precision medicine management. Understanding the distinct and overlapping molecular mechanisms of osteoporosis is essential for improving fracture prevention and long-term skeletal health.<\/jats:p>","DOI":"10.3390\/ijms27020641","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:56:55Z","timestamp":1767877015000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment"],"prefix":"10.3390","volume":"27","author":[{"given":"Kelly I-Rong","family":"Lee","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, MacKay Medical University, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, MacKay Medical University, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-0351","authenticated-orcid":false,"given":"Kuo-Hu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"School of Medicine, Tzu-Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16069","DOI":"10.1038\/nrdp.2016.69","article-title":"Postmenopausal osteoporosis","volume":"2","author":"Eastell","year":"2016","journal-title":"Nat. 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