Background Musculoskeletal disease, which has a complicated relationship with frailty, is a common clinical problem among elderly individuals. Aims This study evaluated the potential causal relationships between osteosarcopenia, osteoarthritis and frailty by Mendelian Randomization (MR) analysis. Methods This study employed a two-sample MR approach to investigate the causal relationships among osteosarcopenia, osteoarthritis and frailty. Published summary statistics were used to obtain instrumental variables at the genome-wide significance level. Results Among the age groups with osteoporosis, high total bone mineral density (TBMD) (45—60, OR = 0.966, 95% CI 0.940–0.993, P = 0.013) and TBMD (over 60, OR = 0.974, 95% CI 0.954–0.994, P = 0.011) reduced the risk of frailty. Similarly, high forearm BMD (FA-BMD), high ultradistal forearm BMD (UFA-BMD), and high Heel-BMD at different sites also reduced the risk of frailty (OR = 0.966, 95% CI 0.936–0.996, P = 0.028; OR = 0.975, 95% CI 0.953–0.997, P = 0.029; OR = 0.981, 95% CI 0.967–0.995, P = 0.008). Among the characteristics related to sarcopenia, grip strength in the left hand, grip strength in the right hand, appendicular lean mass, and walking pace were all protective factors for frailty (OR = 0.788, 95% CI 0.721–0.862, P < 0.001; OR = 0.800, 95% CI 0.737–0.869, P < 0.001; OR = 0.955, 95% CI 0.937–0.974, P = 0.000; OR = 0.480, 95% CI 0.388–0.593, P < 0.001), with low grip strength in those over 60 years of age significantly positively correlated with frailty (OR = 1.168, 95% CI 1.059–1.289, P = 0.002). The MR results of osteoarthritis and frailty revealed a causal relationship between specific joint sites and frailty, including KOA (OR = 1.086, 95% CI 1.017–1.160, P = 0.014), HOA (OR = 1.028, 95% CI 1.007–1.049, P = 0.009), and KOA/HOA (OR = 1.082, 95% CI 1.053–1.113, P = 0.000), increasing the risk of frailty. Conclusion Osteosarcopenia, osteoarthritis and frailty exhibit significant causal effects, rendering them risk factors for frailty. Therefore, in clinical practice, patients with osteosarcopenia and osteoarthritis should be required to undergo relevant interventions to reduce the risk of frailty.

Osteosarcopenia, osteoarthritis and frailty: a two-sample Mendelian randomization study

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2025年4月21日

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Jili Liu,
Xin Xia,
Zhaolin Wang,
Yanqin Wang,
Gang Qin

摘要

Background

Musculoskeletal disease, which has a complicated relationship with frailty, is a common clinical problem among elderly individuals.

Aims

This study evaluated the potential causal relationships between osteosarcopenia, osteoarthritis and frailty by Mendelian Randomization (MR) analysis.

Methods

This study employed a two-sample MR approach to investigate the causal relationships among osteosarcopenia, osteoarthritis and frailty. Published summary statistics were used to obtain instrumental variables at the genome-wide significance level.

Results

Among the age groups with osteoporosis, high total bone mineral density (TBMD) (45—60, OR = 0.966, 95% CI 0.940–0.993, P = 0.013) and TBMD (over 60, OR = 0.974, 95% CI 0.954–0.994, P = 0.011) reduced the risk of frailty. Similarly, high forearm BMD (FA-BMD), high ultradistal forearm BMD (UFA-BMD), and high Heel-BMD at different sites also reduced the risk of frailty (OR = 0.966, 95% CI 0.936–0.996, P = 0.028; OR = 0.975, 95% CI 0.953–0.997, P = 0.029; OR = 0.981, 95% CI 0.967–0.995, P = 0.008). Among the characteristics related to sarcopenia, grip strength in the left hand, grip strength in the right hand, appendicular lean mass, and walking pace were all protective factors for frailty (OR = 0.788, 95% CI 0.721–0.862, P < 0.001; OR = 0.800, 95% CI 0.737–0.869, P < 0.001; OR = 0.955, 95% CI 0.937–0.974, P = 0.000; OR = 0.480, 95% CI 0.388–0.593, P < 0.001), with low grip strength in those over 60 years of age significantly positively correlated with frailty (OR = 1.168, 95% CI 1.059–1.289, P = 0.002). The MR results of osteoarthritis and frailty revealed a causal relationship between specific joint sites and frailty, including KOA (OR = 1.086, 95% CI 1.017–1.160, P = 0.014), HOA (OR = 1.028, 95% CI 1.007–1.049, P = 0.009), and KOA/HOA (OR = 1.082, 95% CI 1.053–1.113, P = 0.000), increasing the risk of frailty.

Conclusion

Osteosarcopenia, osteoarthritis and frailty exhibit significant causal effects, rendering them risk factors for frailty. Therefore, in clinical practice, patients with osteosarcopenia and osteoarthritis should be required to undergo relevant interventions to reduce the risk of frailty.