In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects
Article first published online: 27 JUL 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis Care & Research
Volume 55, Issue 4, pages 551–557, 15 August 2006
How to Cite
Guis, S., Figarella-branger, D., Mattei, J. P., Nicoli, F., Le Fur, Y., Kozak-Ribbens, G., Pellissier, J. F., Cozzone, P. J., Amabile, N. and Bendahan, D. (2006), In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects. Arthritis & Rheumatism, 55: 551–557. doi: 10.1002/art.22100
- Issue published online: 27 JUL 2006
- Article first published online: 27 JUL 2006
- Manuscript Accepted: 31 OCT 2005
- Manuscript Received: 25 JUL 2005
- CNRS. Grant Number: UMR CNRS 6612
- GIS Maladies Rares
- Programme Hospitalier de Recherche Clinique
- 31P magnetic resonance spectroscopy;
- Malignant hyperthermia;
Statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle.
Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P-MRS).
IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P-MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH).
In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.