What question did this study set out to answer?

This study evaluates whether lowering low-density lipoprotein cholesterol (LDL-C) reduces fracture risk and the relationship between LDL-C reduction magnitude and fracture risk.

March 10, 2026Bone and Joint Research0 citationsOpen Access

Unveiling the association between low-density lipoprotein cholesterol lowering and fracture risk

ZWZ. Wen XLXiaoxiao LiCentral South University YWYilun WangCentral South University

Key Points

This study evaluates whether lowering low-density lipoprotein cholesterol (LDL-C) reduces fracture risk and the relationship between LDL-C reduction magnitude and fracture risk.
Population-based cohort study of individuals aged 40 to 90 who initiated statins for hyperlipidaemia from a primary care database
Primary outcome assessed was hip fracture with secondary outcomes being composite fracture and major osteoporotic fracture
Emulation of a hypothetical target trial measuring LDL-C levels at different thresholds after statin initiation within one year over five years.
Lower five-year incident hip fracture risk in LDL-C levels of 1.8 to 2.6 mmol/L (0.53%) and <1.8 mmol/L (0.52%) compared to >2.6 mmol/L (0.65%)
Hazard ratios for incident fractures were 0.77 and 0.68 for the respective LDL-C arms
Decreased risk of recurrent hip fractures noted with HRs of 0.79 and 0.32 for the two lower LDL-C groups
Lowering LDL-C also correlated with reduced risks for composite fracture and major osteoporotic fracture.

Abstract

Aims High serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased risk of fracture; however, it remains unclear whether lowering LDL-C reduces fracture risk, and, if so, whether the magnitude of LDL-C reduction is linearly associated with fracture risk. This study aimed to evaluate the relation between the degree of LDL-C reduction and fracture risk. Methods This population-based cohort study included individuals aged 40 to 90 years who initiated statins for hyperlipidaemia from IQVIA Medical Research Data primary care database in the UK (2000 to 2022). The primary outcome was hip fracture. Secondary outcomes included composite fracture and major osteoporotic fracture. A hypothetical target trial was emulated to assess the effect of achieving a LDL-C level of 1.8 to 2.6 mmol/L or 2.6 mmol/L induced by statin initiation within one year on the risk of incident and recurrent fractures over five years. Results Among 165,242 people with hyperlipidaemia initiating statins (mean age 62.6 years, 51.1% female), the five-year risk of incident hip fracture was lower in the 1.8 to 2.6 mmol/L arm (0.53%) and in the 2.6 mmol/L LDL-C arm (0.65%). The corresponding hazard ratios (HRs) were 0.77 (95% CI 0.65 to 0.91) and 0.68 (95% CI 0.54 to 0.86), respectively. A similar decreased risk of recurrent hip fracture was observed for the 1.8 to 2.6 mmol/L arm (HR = 0.79, 95% CI 0.39 to 1.58) and < 1.8 mmol/L arm (HR = 0.32, 95% CI 0.15 to 0.66), respectively. Additionally, lowering LDL-C levels reduced the risks of composite fracture and major osteoporotic fracture. Conclusion In this population-based cohort study, LDL-C lowering was associated with a decreased risk of fracture in individuals with hyperlipidaemia. This decreased risk appeared to be associated with the extent of LDL-C lowering, suggesting that the therapeutic paradigm of ‘lower is better’ could be advantageous for fracture prevention in individuals with hyperlipidaemia. Cite this article: Bone Joint Res 2026;15(3):227–237.

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