{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:16:28Z","timestamp":1790223388608,"version":"4.1.0"},"reference-count":50,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"unspecified","delay-in-days":91,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-C&T-B-051"],"award-info":[{"award-number":["2023-I2M-C&T-B-051"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2025,9,5]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study uses Mendelian randomisation (MR) to investigate the causal link between SLE and osteoporosis across different ethnic groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic variants associated with SLE were identified from publicly available genome-wide association studies in European and East Asian populations. Two-sample MR (TSMR) analysis and meta-analysis with inverse variance weighting (IVW) assessed their effects on bone mineral density (BMD) and fracture risk. Multivariable MR (MVMR) analysis in East Asians adjusted for potential mediators, and two-step mediation analysis evaluated mediation effects of independent covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A meta-analysis of IVW results from TSMR in East Asian populations revealed a significant positive genetic association of SLE with osteoporosis (OR=1.023, CI 1.007 to 1.040, p&lt;0.01). A similar, although weaker, association was observed in the European population (OR=1.001, CI 1.000 to 1.001, p&lt;0.01). Furthermore, SLE was identified as a risk factor for reduced BMD in both East Asian (\u03b2=\u22120.0690, p&lt;0.05) and European (\u03b2=\u22120.0109, p&lt;0.05) populations, and for fracture risk in European (OR=1.002, p&lt;0.05) populations, while no significant association was observed in the East Asian population (OR=1.010, p=0.705). MVMR analysis of East Asian data assessed mediation effects and found that the SLE-osteoporosis association was nullified after adjusting for cardiovascular disease and health status. Mediation analysis identified low-density lipoprotein cholesterol (LDL-C) and anti-inflammatory medication use as independent mediators, with mediation effects of 0.1170 and 0.0510, respectively. No significant heterogeneity or pleiotropy was detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SLE appears to be a causal risk factor for osteoporosis. LDL-C and anti-inflammatory medication use mediate this relationship, suggesting the importance of managing these factors in patients with SLE to reduce osteoporosis risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2025-001735","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T06:00:48Z","timestamp":1759212048000},"page":"e001735","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Potential causal effect of SLE on osteoporosis, and the mediation effect: a Mendelian randomisation study"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0552-3831","authenticated-orcid":false,"given":"Zhaoqing","family":"Wang","sequence":"first","affiliation":[{"name":"Vanke School of Public Health, Tsinghua University, Beijing, China"},{"name":"Institute for Healthy China, Tsinghua University, Beijing, 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