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Summary-level data from the Genome-Wide Association Study (GWAS) were used. Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls). Bone mineral density (BMD) at five different sites (heel (<jats:italic>n<\/jats:italic>\u2009=\u2009426,824), total body (TB) (<jats:italic>n<\/jats:italic>\u2009=\u200956,284), forearm (FA) (<jats:italic>n<\/jats:italic>\u2009=\u20098143), femoral neck (FN) (<jats:italic>n<\/jats:italic>\u2009=\u200932,735), and lumbar spine (LS) (<jats:italic>n<\/jats:italic>\u2009=\u200928,498)) was used as a phenotype for OP. Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods. Related sensitivity analyses were performed. Myopia was also analyzed as a negative control result to ensure the validity of IVs. Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta\u2009=\u20090.06, <jats:italic>p<\/jats:italic>\u2009=\u20090.03; TB-BMD-related analysis: beta\u2009=\u20090.18, <jats:italic>p<\/jats:italic>\u2009=\u20098.72E-08; FN-BMD-related analysis: beta\u2009=\u20090.15, <jats:italic>p<\/jats:italic>\u2009=\u20094.89E-03; LS-BMD-related analysis: beta\u2009=\u20090.16, <jats:italic>p<\/jats:italic>\u2009=\u20091.43E-04]. There was no evidence of a significant causal effect of IVDD on BMD. In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.<\/jats:p>","DOI":"10.1007\/s00223-023-01165-1","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T17:01:46Z","timestamp":1700240506000},"page":"228-236","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intervertebral Disk Degeneration and Bone Mineral Density: A Bidirectional Mendelian Randomization Study"],"prefix":"10.1007","volume":"114","author":[{"given":"Jie","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengrui","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"1165_CR1","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1007\/s00586-019-06029-7","volume":"28","author":"K Alpantaki","year":"2019","unstructured":"Alpantaki K, Kampouroglou A, Koutserimpas C, Effraimidis G, Hadjipavlou A (2019) Diabetes mellitus as a risk factor for intervertebral disc degeneration: a critical review. 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