ArticlePloS one2024
Association of lipid-lowering drugs with osteoarthritis outcomes from a drug-target Mendelian randomization study.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- Using Mendelian randomization analyses in osteoarthritis: state of art and future perspectives.Annals of medicine · 2025Pooled it
- Impact of IL-6 receptor inhibitors on cerebrospinal fluid metabolites in type 2 diabetes patients.Medicine · 2026Article
- Pathological mechanisms of osteoarthritis in the network of geriatric comorbidities: Emerging insights from organs-crosstalk.Journal of orthopaedic translation · 2026Review
- Revisiting the Subtle Relationship Between Metabolic Syndrome and Osteoarthritis.Journal of inflammation research · 2026Review
- Causal relationship between statins and hemorrhagic stroke: A drug-target Mendelian randomization analysis.Medicine · 2025Article
- Phospholipids and Sphingolipids in Osteoarthritis.Biomolecules · 2025Review
- Pyroptosis for osteoarthritis treatment: insights into cellular and molecular interactions inflammatory.Frontiers in immunology · 2025Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteoarthritis (OA), a prevalent musculoskeletal disorder, has been suggested to have a potential association with metabolic syndrome, particularly lipid metabolism. Studies exploring the effects of lipid-lowering drugs on OA have yielded conflicting results.
objectiveThis study employed a drug-targeted Mendelian randomization approach to investigate the association between genetically predicted lipid-modulating effects of commonly targeted lipid-lowering agents and the risk of OA, with the aim of providing a theoretical foundation for the use of lipid-lowering drugs in OA treatment.
methodsEmploying Mendelian randomization (MR) analysis, we examined the potential causal relationship between lipid-lowering drugs and OA. Genetic variants associated with LDL cholesterol levels were selected from the GWAS summary data, and a series of statistical analyses, including inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, were performed to estimate causal effects.
resultsWe observed significant associations between genetically proxied lipid-lowering drug targets and OA risk. Notably, HMGCR-mediated LDL cholesterol showed an association with overall OA of the hip or knee (OR = 0.865, 95%CI: 0.762 to 0.983, p = 0.026, q = 0.07) and knee osteoarthritis specifically (OR = 0.746, 95%CI: 0.639 to 0.871, p = 2.180×10-4, q = 0.004). PCSK9-mediated LDL cholesterol also demonstrated an association with OA of the hip or knee (OR = 0.915, 95%CI: 0.847 to 0.988, p = 0.023, q = 0.07) and knee osteoarthritis (OR = 0.901, 95%CI: 0.821 to 0.990, p = 0.03, q = 0.07). NPC1L1-mediated LDL cholesterol showed a positive association with OA of the hip or knee (OR = 1.460, 95%CI: 1.127 to 1.890, p = 0.004, q = 0.033). Furthermore, LDLR-mediated LDL cholesterol demonstrated an association with OA of the hip or knee (OR = 0.882, 95%CI: 0.788 to 0.988, p = 0.03, q = 0.07) and hip osteoarthritis (OR = 0.867, 95%CI: 0.769 to 0.978, p = 0.02, q = 0.07).
conclusionsThese findings provide preliminary evidence for the potential therapeutic use of lipid-lowering drugs in OA treatment. Further investigation is needed to validate these findings and explore the precise mechanisms underlying the observed associations.
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