{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:07:58Z","timestamp":1779340078576,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis in women is strongly influenced by menopause, a major physiological transition that reshapes bone metabolism. Although low bone mineral density (BMD) in premenopausal women and osteoporosis in postmenopausal women share the clinical outcome of skeletal fragility, it remains unclear whether they reflect a shared molecular program or distinct regulatory mechanisms. Here, we compared genetic signals associated with premenopausal and postmenopausal low BMD in Korean women using two independent genotyping platforms with distinct variant coverage. After allele harmonization and heterogeneity testing, variants were classified as reversal signals, showing directionally discordant effects across menopausal status, or stable signals, showing concordant effects. Gene-level association analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA), followed by functional enrichment and network-based analyses. Reversal and stable signals showed distinct biological patterns. Reversal signals consistently converged on cyclic nucleotide-related pathways, including cyclic adenosine monophosphate\/cyclic guanosine monophosphate (cAMP\/cGMP) signaling and nitric oxide-mediated processes, whereas stable signals were more broadly distributed across pathways related to ion homeostasis, cell\u2013substrate adhesion, and structural maintenance. These pathway-level patterns were reproducible across platforms despite limited SNP-level overlap. These findings suggest that low BMD across the menopausal transition is better resolved at the gene and pathway levels than at the level of individual SNPs.<\/jats:p>","DOI":"10.3390\/ijms27104447","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathway-Level Reorganization of Genetic Signals Associated with Low Bone Mineral Density Across the Menopausal Transition"],"prefix":"10.3390","volume":"27","author":[{"given":"Soo-Eun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Cheonan Chungmu Hospital, Cheonan 31144, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Kang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, Catholic Kwandong University, Gangneung 25601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-3136","authenticated-orcid":false,"given":"Gyutae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Radiology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-5188","authenticated-orcid":false,"given":"Ju Yeon","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Dental Pharmacology, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-2304","authenticated-orcid":false,"given":"Sang Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.6118\/jmm.300001","article-title":"The 2024 Guidelines for Osteoporosis\u2014Korean Society of Menopause: Part I","volume":"30","author":"Lee","year":"2024","journal-title":"J. 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