Muscle- and skeletal-related side-effects of statins: tip of the iceberg?

Abstract

The clinical spectrum of muscle- and skeletal-related side-effects of statins includes varied myalgias and weakness, an asymptomatic increase in the concentration of creatine kinase and other biochemical parameters, myositis and rhabdomyolysis. Currently, there is no consensus on the definition of 'statin myopathy'. Evidence suggests that deleterious effects may also be associated with the volume or dosage of structured exercise and/or the intensity of physical activity. Moreover, non-muscle adverse effects on the joints and tendons are often overlooked and underemphasized. The incidence of myopathy associated with statin treatment typically ranges between 1.5% and 10%. Few data are available regarding the prevalence of muscle- related symptoms associated with different statins and the distribution of affected muscles. Furthermore, discrepancies between clinical trials and daily practice may emanate, in part, because of inconsistent definitions or exclusion criteria.The pathophysiology of statin-related myopathy is incompletely understood. A dose-dependent and proapoptotic effect, direct effects on mitochondria, drug interactions and genetic factors, or combinations thereof, may be involved. Recently, a rare immune-mediated myopathy triggered by statin use has been described. With the increasing number of patients treated with statins and with more patients being prescribed high doses of potent statins to achieve low-density lipoprotein targets, muscle-related side-effects will become more prevalent. Currently, the only effective treatment is the discontinuation of statin use. Further research is needed to develop alternative LDL-lowering drugs when statins are not well tolerated and to establish additional effective strategies to manage lipids and lipoproteins.

Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design

“…Crystals of complex 2 were grown at 18°C by mixing equal volumes of the complex solution preincubated with 5.8 mM CYMAL-5 (Anagrade) and 5.5 mM tris(carboxyethyl)phosphine exact anticancer mechanism of statins remains unclear, yet recent data show that they affect the adhesion, invasion, and migration processes and induce apoptosis of cancer cells by disrupting integrity of lipid rafts in their membrane (26)(27)(28)(29)(30)(31)(32). However, by blocking an early step in the pathway, statins affect not only production of cholesterol but also the formation of other physiologically important compounds [e.g., ubiquinone, dolichols, prenylated proteins (33)], and therefore, in long-term use, can cause dose-dependent side effects [mainly myopathy (34)(35)(36)(37)] leading to discontinuation of treatment in up to 20% of patients (38,39). Also, because, due to uptake transporters, statins generally target the liver (where 70% of cholesterol is synthesized), in clinical trials for cancer they have to be used at much higher doses (33) to reach other organs and tissues.…”

Editor’s presentation

“…Furthermore, given that RYR supplements may contain prescriptionlevel doses of statins, these supplements may pose risks to consumers similar to those of prescription statins. 6 A growing body of evidence indicates that mobile technology can support behaviour change, yet robust evidence for the effectiveness of smartphone interventions is lacking. 7 SaltSwitch is a free app for smartphone, which enables users to receive an immediate, interpretive traffic light nutrition label on the screen, along with a list of lower salt alternatives to 'switch' to.…”

Statin-induced Myopathy

“…Drug interactions, genetic predisposition, depletion of metabolites in the mevalonate pathway, mitochondrial dysfunction, dysregulation of apoptosis and protein degradation and immune mechanisms have all been implicated. (10) The muscle ache and/or muscle weakness associated with a statin myopathy is most often bilateral, but may be asymmetrical. It predominantly affects large muscle groups around the shoulders, hips, thighs and/or calves.…”

“…Although the patient cannot usually identify a precipitating factor, recent strenuous or unaccustomed exercise, or an alteration in medication may be reported. (10) There are no specific clinical signs that accompany the pain. The serum CK should be measured and may be elevated.…”

“…(27) Statin treatment may be recommenced in patients whose symptoms do not improve after a period of withdrawal, dependent upon a risk-benefit evaluation. (10) ■ Consider altering the statin treatment: Existing statin treatment may be altered by:…”