Statin-Induced Musculoskeletal Problems: Disconcerting Reports and Data

Abstract

Statins are molecules of fungal origin, which inhibit the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme, a key step in the sterol biosysnthesis, rendering them powerful cholesterol lowering medications contributing to significant prevention of cardiovascular disease. 1 Statins are characterized by differences in bioavailability, lipo/hydrophilicity, cytochrome P-450 mediated metabolism and cellular transport mechanisms, differences that are reflected in their relative capacity in LDL-cholesterol lowering and possibly in parenchymal or muscular toxicities. 2 Statin intolerance comprises, among others, musculoskeletal problems, such as statin-induced muscle and tendon disorders which are the most common cause of statin discontinuation. 3-10 Musculoskeletal Problems Statin therapy has long been associated with musculoskeletal (MS) problems in approximately 10% - 25% of patients treated in real-world clinical practice, but such problems have rarely been reported in controlled clinical trials, 3,4 and their incidence has thus far been underestimated. 5 Studies have concentrated on creatine kinase (CK) elevations to identify myopathy. However, many patients can have normal serum CK levels despite myalgia and persistent weakness and muscle biopsy - proven myopathy. Discontinuation of statin and rechalllenge may be required to prove that it is statin-related. Several risk factors may predispose patients to statin-related MS problems, including advanced age, family history of myopathy, statin dose, and interacting medications (e.g., azole antifungals, cimetidine, fibrates, macrolide antibiotics, protease inhibitors and cyclosporine) (Table 1). 5,6,8 Musculoskeletal conditions, arthropathies, injuries, and pain appear to be more common among statin users than among similar nonusers... (excerpt)