Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses

Abstract

Osteoporosis is a known risk factor for rotator cuff tears (RCTs), but the causal correlation and underlying mechanisms remain unclear. This study aims to evaluate the impact of osteoporosis on RCT risk and investigate their genetic associations. Using data from the UK Biobank (n = 457 871), cross-sectional analyses demonstrated that osteoporosis was significantly associated with an increased risk of RCTs (adjusted OR [95% CI] = 1.38 [1.25–1.52]). A longitudinal analysis of a subset of patients (n = 268 117) over 11 years revealed that osteoporosis increased the risk of RCTs (adjusted HR [95% CI] = 1.56 [1.29–1.87]), which is notably varied between sexes in sex-stratified analysis. Causal inference methods, including propensity score matching, inverse probability weighting, causal random forest and survival random forest models further confirmed the causal effect, both from cross-sectional and longitudinal perspectives. A colocalization analysis across multiple datasets identified six candidate loci, including the successfully replicated PKDCC rs12996954 variant, which may help explain the shared genetic basis between osteoporosis and RCTs. In conclusion, osteoporosis significantly increases the risk of RCTs, emphasizing the importance of osteoporosis management in preventing RCTs. The identification of shared genetic loci provides new insights into their potential pathogenic mechanisms.

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Funding

Fundamental Research Funds for the Central Universities 2024ZYGXZR077, 2025ZYGXZR002), Guangdong Basic and Applied Basic Research Foundation (2023B1515120006), Guangzhou Basic and Applied Basic Research Foundation (2024A04J5776), the Research Fund (2023QN10Y421), Guangzhou Talent Recruitment Team Program (2024D03J0004)

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