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      We appreciate the observations of Hyman and Al-shekhlee. Given the limits of creatine kinase in detecting statin-associated muscle disorders, Hyman correctly points out the need for alternative screening tests for this disorder. As yet, no biomarker is sufficiently sensitive or specific to be used routinely to diagnose statin myotoxicity. Skeletal troponins,
      • Simpson J.A.
      • Labugger R.
      • Hesketh G.G.
      • et al.
      Differential detection of skeletal troponin I isoforms in serum of a patient with rhabdomyolysis: markers of muscle injury?.
      lipidomics analyses,
      • Laaksonen R.
      • Katajamaa M.
      • Paiva H.
      • et al.
      A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.
      and urinary organic acid profiles
      • Phillips P.S.
      • Haas R.H.
      • Barshop B.
      • et al.
      Utility of abnormal 3-methylglutaconic aciduria (3MGA) in diagnosing statin associated myopathy.
      each hold some promise and remain under evaluation. In the meanwhile we must depend on a combination of clinical criteria described in the article, including typical symptoms, dynamometer-measured weakness, abnormalities on cardiopulmonary exercise, and a constellation of tests excluding other disorders to arrive at this diagnosis.
      The patient evaluation plan we recommended included the approach to patients with less serious muscle symptoms while receiving statins, as well as to patients with muscle symptoms after statin-induced rhabdomyolysis.
      • Antons K.
      • Williams C.
      • Baker S.K.
      • Phillips P.S.
      Clinical perspectives of statin-induced rhabdomyolysis.
      Although a negative electromyogram has not been useful in distinguishing patients with purported statin-induced muscle pain and weakness, it is certainly useful in distinguishing inflammatory from other causes of acute rhabdomyolysis. The most common reason for muscle biopsy in patients with persistent symptoms after suspected statin-induced rhabdomyolysis is to exclude polymyositis or an underlying metabolic myopathy. We agree with Al-shekhlee and Katirji that a negative electromyogram will exclude the former. We do not agree that a negative electromyogram obviates a muscle biopsy in patients with persistent symptoms after rhabdomyolysis. A significant number of these patients have metabolic muscle disease, as we recently observed.
      • Vladutiu G.D.
      • Simmons Z.
      • Isackson P.J.
      • et al.
      Genetic risk factors and metabolic myopathies associated with lipid-lowering drugs.
      Both correspondents point to the complexity in evaluating and treating statin-induced muscle disorders that continues to make work in this area both challenging and controversial. Fear of serious muscle toxicity remains the most common reason that our patients and colleagues are not compliant with aggressive lipid-lowering recommendations. Further work to clarify the mechanism by which lipid-lowering therapies cause muscle toxicity is essential for the appropriate application of lipid-lowering therapies.

      References

        • Simpson J.A.
        • Labugger R.
        • Hesketh G.G.
        • et al.
        Differential detection of skeletal troponin I isoforms in serum of a patient with rhabdomyolysis: markers of muscle injury?.
        Clin Chem. 2002; 48: 1112-1114
        • Laaksonen R.
        • Katajamaa M.
        • Paiva H.
        • et al.
        A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.
        PLoS ONE. 2006; 1: e97
        • Phillips P.S.
        • Haas R.H.
        • Barshop B.
        • et al.
        Utility of abnormal 3-methylglutaconic aciduria (3MGA) in diagnosing statin associated myopathy.
        Arterioscler Thromb Vasc Biol. 2002; 22: 878
        • Antons K.
        • Williams C.
        • Baker S.K.
        • Phillips P.S.
        Clinical perspectives of statin-induced rhabdomyolysis.
        Am J Med. 2006; 119: 400-409
        • Vladutiu G.D.
        • Simmons Z.
        • Isackson P.J.
        • et al.
        Genetic risk factors and metabolic myopathies associated with lipid-lowering drugs.
        Muscle Nerve. 2006; 34: 153-162

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