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)