Unveiling the Association Between Low-Density Lipoprotein Cholesterol Lowering and Fracture Risk Among Patients with Hyperlipidaemia in a Population-Based Cohort Study: The Lower, the Better

Zeqin Wen¹, Yilun Wang¹, Xiaoxiao Li², Yuqing Zhang³, Junqing Xie⁴, Houchen Lyu⁵, Changjun Li², Jie Wei⁶, Guanghua Lei⁷ and Chao Zeng⁸, ¹Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China (People's Republic), ²Central South University, Changsha, China (People's Republic), ³Massachusetts General Hospital, Quincy, MA, ⁴University of Oxford, Oxford, United Kingdom, ⁵Central South University, Beijing, China, ⁶Department of Orthopaedics, Xiangya Hospital, Central South University; Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University; Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University; Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China (People's Republic), ⁷Department of Orthopaedics, Xiangya Hospital, Central South University; Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University; Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China (People's Republic), ⁸Department of Orthopaedics, Xiangya Hospital, Central South University; Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University; Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University; Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China (People's Republic)

Meeting: ACR Convergence 2024

Keywords: bone biology, Bone density, Cohort Study, Fracture, osteoporosis

Session Information

Date: Monday, November 18, 2024

Title: Osteoporosis & Metabolic Bone Disease – Basic & Clinical Science Poster

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: High low-density lipoprotein cholesterol (LDL-C) is a major risk factor for fracture; however, whether LDL-C lowering induced by statins is associated with decreased fracture risk remains controversial, frequently influenced by indication bias. We emulated a randomized target trial to evaluate the relation between LDL-C lowering and fracture risk, particularly concerning the extent of LDL-C lowering, among patients with hyperlipidaemia.

Methods: Individuals aged 40 to 90 years old who initiated statin therapy for hyperlipidaemia were included from the IQVIA Medical Research Data primary care database in the United Kingdom, 2000-2022. We emulated analyses of a hypothetical target trial using a “cloning, censoring, and weighting” approach to assess the effects of achieving the target level of 2.6 mmol/L (1.8 mmol/L≤ LDL-C ≤2.5 mmol/L) or lower target level of 1.8 mmol/L (LDL-C < 1.8 mmol/L) within 1 year after statin initiation on the primary outcome (i.e., incident and recurrent hip fracture) and secondary outcomes (i.e., incident and recurrent composite fracture and major osteoporotic fracture) over 5-year follow-up, respectively (Figure 1).

Results: Among 165,242 people with hyperlipidaemia (mean age 62.6 years, women 51.1%), the 5-year risk of incident hip fracture was lower in the “1.8-2.6 mmol/L” arm (0.53%) and in the “< 1.8 mmol/L” arm (0.52%) than the “ >2.6 mmol/L LDL-C” arm (0.65%) The corresponding hazard ratios (HRs) were 0.77 (95% confidence interval [CI]: 0.65-0.91) and 0.68 (95% CI: 0.54-0.86), respectively (Figure 2). A similar decreased risk of recurrent hip fracture was observed for the “1.8-2.6 mmol/L” arm (HR=0.79, 95% CI: 0.39-1.58) and “< 1.8 mmol/L” arm (HR=0.32, 95% CI: 0.15-0.66) compared with the “ >2.6 mmol/L” arm, respectively. Additionally, lowering LDL-C levels reduced the risks of composite fracture and major osteoporotic fracture. (Figure 3).

Conclusion: In this population-based study, the extent of LDL-C lowering was associated with a decreased risk of fracture in individuals with hyperlipidaemia, suggesting that the therapeutic paradigm of “lower is better” could be advantageous for fracture prevention in individuals with hyperlipidaemia. Additional studies, including RCTs, will be needed to corroborate our findings and explore the therapeutic potential of statins for decreasing fracture risk among patients with hyperlipidaemia.

Figure 1. Study design of a hypothetical randomized controlled trial (“target trial”) on which we modeled our observational data analysis (A); Cloning and censoring in five hypothetical patients (B). For example, patient C achieved the target of “1.8 mmol/L≤ LDL-C ≤2.6 mmol/L” within 1 year after statin initiation. The replicate of patient C assigned to the “1.8 mmol/L≤ LDL-C ≤2.6 mmol/L” arm was adhered to his/her assignment. However, the other two replicates of patient C, assigned to the “LDL-C >2.6 mmol/L” and “LDL-C <1.8 mmol/L” arms, deviated from their assignments and were censored when the LDL-C level was measured. During the grace period, if an individual experienced a fracture, was lost to follow-up, or died before achieving the therapeutic target (e.g., patient B or D), that person was considered adhering to his/her assignment in all arms, and the fracture or death was counted in each of the assigned arms.

Figure 2. 5-year risk of incident hip fracture (A) and recurrent hip fracture (B) for “LDL-C >2.6 mmol/L”, “1.8 mmol/L≤ LDL-C ≤2.6 mmol/L” and “LDL-C <1.8 mmol/L” arms among patients with hyperlipidaemia initiating statin.

Figure 3. 5-year risk of incident composite fracture (A), recurrent composite fracture (B), incident major osteoporotic fracture (C), and recurrent major osteoporotic fracture (D) for “LDL-C >2.6 mmol/L”, “1.8 mmol/L≤ LDL-C ≤2.6 mmol/L” and “LDL-C <1.8 mmol/L” arms among patients with hyperlipidaemia initiating statin.

Disclosures: Z. Wen: None; Y. Wang: None; X. Li: None; Y. Zhang: None; J. Xie: None; H. Lyu: None; C. Li: None; J. Wei: None; G. Lei: None; C. Zeng: None.

To cite this abstract in AMA style:

Wen Z, Wang Y, Li X, Zhang Y, Xie J, Lyu H, Li C, Wei J, Lei G, Zeng C. Unveiling the Association Between Low-Density Lipoprotein Cholesterol Lowering and Fracture Risk Among Patients with Hyperlipidaemia in a Population-Based Cohort Study: The Lower, the Better [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/unveiling-the-association-between-low-density-lipoprotein-cholesterol-lowering-and-fracture-risk-among-patients-with-hyperlipidaemia-in-a-population-based-cohort-study-the-lower-the-better/. Accessed .

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/unveiling-the-association-between-low-density-lipoprotein-cholesterol-lowering-and-fracture-risk-among-patients-with-hyperlipidaemia-in-a-population-based-cohort-study-the-lower-the-better/