Osteoporosis and chronic tendinopathy: a two-sample Bidirectional Mendelian randomization

BACKGROUND The incidence of osteoporosis rises with advancing age, and it has emerged as a significant global public health issue, often presenting clinically with symptoms such as pain, kyphosis, reduced height, and fractures.Chronic tendinopathy is a common orthopedic disease, which is mainly characterized by pain, delayed and difficult to heal, causing great pain to patients. Preliminary epidemiological studies have investigated the potential association between osteoporosis and chronic tendinopathy; however, a definitive causal relationship has yet to be established. With increasing life expectancy and an accelerating aging population, the burden of osteoporosis and chronic tendinopathy is expected to rise significantly, with important implications for morbidity and mortality. METHODS Instrumental variables were selected from the IEU GWAS database of summary statistics. Five different bone mineral density (BMD) sites—heel, total body, femoral neck, lumbar spine, and ultradistal forearm BMD—along with total body BMD across five age groups (0–15, 15–30, 30–45, 45–60, and over 60 years) were utilized as osteoporosis phenotypes. Achilles tendinitis, Bicipital tendinitis, Calcific tendinitis, Calcific tendinitis of shoulder, Gluteal tendinitis, Patellar tendinitis were selected, Peroneal tendinitis represent Chronic tendinopathy phenotypes. Multiple analytical methods were employed to comprehensively assess the causal relationship between chronic tendinopathy and osteoporosis. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and 'leave-one-out' analysis, were conducted to verify the robustness of the findings. RESULTS Mendelian Randomization analysis revealed a significant causal relationship between five different sites of BMD and Calcific tendinitis of the shoulder; Additionally, MR demonstrated a significant causal relationship between Heel BMD, Lumbar spine BMD and Peroneal tendinitis. In the Mendelian Randomization analysis examining age-related bone mineral density (BMD) and chronic tendinopathy, significant causal relationships were identified between total body BMD in the age groups 0–15 years, 45–60 years, and over 60 years with calcific tendinitis of the shoulder.. In all inverse analyses, no significant causal association between chronic tendinopathy and osteoporosis was observed. The reliability of these results was confirmed through sensitivity analyses. CONCLUSION Osteoporosis may be a potential etiological factor for chronic tendinopathy, with a significant causal relationship observed between BMD and chronic tendinopathy, particularly in individuals over 45 years of age. This suggests that patients presenting with chronic tendinopathy may have an underlying issue of osteoporosis. Therefore, routine bone mineral density (BMD) screening is recommended for individuals over 45 years of age who present with chronic tendinopathy.