Low back pain is a leading global cause of disability, and the musculoskeletal impact of lipid-lowering drugs (e.g., statins, PCSK9 inhibitors) used for coronary heart disease (CHD) prevention has garnered attention. However, the causal relationship between lipid-lowering drug target inhibition and LBP risk remains unclear.
Here, a Mendelian randomization study investigated the association between inhibition of HMGCR, PCSK9, and NPC1L1 (key lipid-lowering targets) and LBP risk. Results showed PCSK9 inhibitors may reduce LBP risk, while HMGCR and NPC1L1 inhibitors had no significant association. Using CHD as a positive control, the study validated the reliability of findings, confirming known lipid-lowering effects on CHD risk.
This work provides the first genetic evidence for the musculoskeletal safety of HMGCR and NPC1L1 inhibitors, suggests potential LBP benefits of PCSK9 inhibitors, and opens new directions for exploring PCSK9 pleiotropy (e.g., anti-inflammatory, neuroprotective effects). The work entitled “Genetically proxied inhibition of lipid-lowering drug targets and risk of low back pain: A Mendelian randomization study” was published on Healthcare and Rehabilitation (published on October 16, 2025).
DOI
10.1016/j.hcr.2025.100053