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In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects.
- Source :
-
Arthritis and rheumatism [Arthritis Rheum] 2006 Aug 15; Vol. 55 (4), pp. 551-7. - Publication Year :
- 2006
-
Abstract
- Objective: 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.<br />Methods: 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).<br />Results: 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).<br />Conclusion: In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.
- Subjects :
- Aged
Biopsy
Calcium metabolism
Female
Humans
Hypercholesterolemia drug therapy
Magnetic Resonance Spectroscopy
Male
Middle Aged
Muscle Contraction drug effects
Muscle, Skeletal drug effects
Muscle, Skeletal pathology
Muscular Diseases chemically induced
Muscular Diseases pathology
Pain
Creatine Kinase blood
Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects
Muscle, Skeletal metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0004-3591
- Volume :
- 55
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 16874775
- Full Text :
- https://doi.org/10.1002/art.22100