Causal relationship between osteoporosis and osteoarthritis: A two-sample Mendelian randomized study

Area of Science:

• Genetics
• Epidemiology
• Rheumatology

Background:

• Clinical studies suggest an inverse relationship between osteoporosis (OP) and osteoarthritis (OA).
• The genetic basis for the inverse relationship between OP and OA remains unproven.
• Understanding this genetic link is crucial for predicting OA risk and developing targeted interventions.

Purpose of the Study:

• To investigate the potential causal effect of osteoporosis on osteoarthritis using a genetic prediction approach.
• To clarify the genetic relationship between OP and OA subtypes (total, knee, and hip) through Mendelian randomization analysis.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted using publicly available genetic data.
• Inverse variance weighted (IVW), weighted median, MR-Egger, and MR-RAPS methods were employed to assess causal effects.
• Sensitivity analyses including MR-PRESSO and leave-one-out tests were performed to evaluate pleiotropy and heterogeneity.

Main Results:

• Osteoporosis was found to have a causal, protective effect on total osteoarthritis (OR=0.751, P<0.016).
• Genetic prediction of OP was negatively correlated with knee osteoarthritis (KOA) (IVW: OR=0.002, P<0.016).
• OP demonstrated a protective effect against hip osteoarthritis (OR=4.15e-3, P=3.99e-3).

Conclusions:

• Osteoporosis exerts a protective effect against the incidence of osteoarthritis, including knee and hip OA.
• The genetic evidence supports a causal relationship where OP reduces OA risk.
• These findings have implications for understanding OA pathogenesis and potential therapeutic strategies.