Statins: bitter enemies of tendons or not? A systematic review of clinical evidence

G. Anzillotti, F. Vespasiano, F. Öttl, P. Conte, M. Minelli, G.F. Raspugli, S. Svensson Di Giorgio, R. Valente, E. Kon, B. Di Matteo

IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. marcomariaminelli@gmail.com

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• Orthopedics

OBJECTIVE: Tendon tears cause significant disability, especially in the elderly. Lipid metabolism was shown to play a role in tendon tear pathogenesis. Statins, which lower cholesterol levels, have been associated with tendinopathies and tendon tears as possible adverse events. This systematic review evaluates the association between statin use and tendon rupture risk, as well as statins’ influence on tendon healing after repair.

MATERIALS AND METHODS: A literature search was conducted on PubMed, Embase, and Google Scholar databases using specific search strings related to statins and tendons. The inclusion criteria included randomized controlled trials (RCTs), retrospective or prospective studies on humans, articles written in English, papers published in indexed journals, and articles evaluating the relationship between statins and tendons. The quality of RCTs was assessed through the Cochrane Risk of Bias tool, while the risk of bias for non-randomized studies was evaluated according to the modified ROBINS-I tool.

RESULTS: Twelve studies were included; eight studies investigated statin effects on native tendons, and four evaluated outcomes after tendon repair. Across over 1 million patients, a large cohort study found no significant increase in the risk of native tendon rupture among statin users (HR 0.95, 95% CI 0.84-1.08). Conversely, a retrospective study found that hyperlipidemic patients treated with statins had a significantly higher retear rate after rotator cuff repair compared to the control group (OR 6.5, p < 0.001). Furthermore, statin use was associated with an increased risk of tendinopathies, including trigger finger (HR 1.435), radial styloid tenosynovitis (HR 1.365), and Achilles tendinitis (HR 1.516) (p < 0.0001 for all). However, protective effects were observed for rotator cuff disease with rosuvastatin (HR 0.41, p < 0.0001).

CONCLUSIONS: The effect of statins on tendons may be modulated by variables such as sex, tendon type, statin formulation, and comorbidities. Hence, statin therapy does not universally increase tendon rupture risk but may influence tendon integrity and healing in a patient-specific manner. Further high-quality studies are needed to define these relationships better and optimize clinical recommendations.

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