{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:37:43Z","timestamp":1790318263746,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008108","name":"Taipei Tzu-Chi Hospital","doi-asserted-by":"publisher","award":["TCRD-TPE-115-46"],"award-info":[{"award-number":["TCRD-TPE-115-46"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a prevalent metabolic bone disorder characterized by reduced bone mass, compromised microarchitecture, and increased fracture risk. Its pathogenesis extends beyond simple bone mineral density (BMD) loss and reflects complex disruptions in bone remodeling governed by osteoblast\u2013osteoclast coupling and systemic metabolic factors. This review lays particular emphasis on diabetes mellitus-related osteoporosis (DOP) and estrogen deficiency-induced osteoporosis (EDOP), discussing bone remodeling between osteoclastogenesis and osteoblast differentiation regulated by key signaling pathways, including the RANKL\/RANK\/OPG, Wnt\/\u03b2-catenin, BMP\u2013Smad, Hedgehog, and inflammatory cytokine networks. This review then explores how chronic hyperglycemia, insulin deficiency or resistance, oxidative stress, ferroptosis, advanced glycation end products, and low-grade inflammation disrupt bone homeostasis in diabetes, resulting in impaired bone quality and elevated fracture risk, particularly in type 2 diabetes. In parallel, we discuss the genomic and non-genomic actions of estrogen in maintaining skeletal integrity and elucidate how estrogen deficiency accelerates bone resorption and suppresses bone formation through altered cytokine signaling, oxidative stress, and impaired mechanotransduction. Advances in diagnostic strategies beyond BMD, including trabecular bone score, high-resolution peripheral quantitative computed tomography, and emerging biomarkers, are reviewed. Finally, this review summarizes current and emerging therapeutic approaches tailored to DOP and EDOP, emphasizing the need for mechanism-based, individualized management. A deeper understanding of these shared and distinct pathways may facilitate improved risk stratification and the development of targeted interventions for osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms27031453","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:00:33Z","timestamp":1770022833000},"page":"1453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Osteoporosis in Patients with Pre-Existing Diabetes Mellitus and in Women with Estrogen Deficiency: A Molecular and Cellular Perspective"],"prefix":"10.3390","volume":"27","author":[{"given":"Chin-Yen","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 10421, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 10421, Taiwan"},{"name":"Department of Mechanical Engineering, National Yang Ming Chiao Tung University, Hsinchu 30009, 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":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Su, W., Jia, H., Yang, L., Zhang, J., Wei, Z., Tsikwa, P., and Wang, Y. 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