VA Study Links Statins to Musculoskeletal Conditions, Injuries

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By Brenda L. Mooney

DALLAS — Adverse effects from statin therapy go beyond just muscle pain and weakness, also increasing risks of musculoskeletal conditions, arthropathies and injuries, according to a new VA study using a large military medical database.

The original investigation, published online by JAMA Internal Medicine, said the association appeared strongest in physically active individuals, which was especially relevant to the military population.

“Active-duty soldiers and veterans have been reported to have a high prevalence of musculoskeletal diseases that exceeds that of the general population, which may be related to their strenuous muscular activity,” according to the study led by Ishak Mansi, MD, of the Veteran Affairs North Texas Health Care System, Dallas. “The increased risk of injury in our population suggests that statin therapy may compromise soldiers’ musculoskeletal preparedness.”

Using data from San Antonio-based beneficiaries of TRICARE, investigators looked at the effect on musculoskeletal conditions based on statin use during the 2005 fiscal year.

For the study, patients were divided into two groups: 6,967 statin users for at least 90 days and the same number of nonusers.

The chances for any musculoskeletal disease diagnosis in those taking statins was found to be significantly higher when compared with nonusers (odds ratio 1.19), according to the study.

“Musculoskeletal conditions, arthropathies, injuries and pain are more common among statin users than among similar nonusers. The full spectrum of statins’ musculoskeletal adverse events may not be fully explored, and further studies are warranted, especially in physically active individuals,” the authors wrote.

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Based on ICD-9-CM codes, statin users had a higher odds ratio (OR) for musculoskeletal disease diagnosis group 1 (all musculoskeletal diseases: OR, 1.19), for musculoskeletal disease diagnosis group 1b (dislocation/strain/sprain: OR, 1.13) and for musculoskeletal diagnosis group 2 (musculoskeletal pain: OR, 1.09), but not for musculoskeletal disease diagnosis group 1a (osteoarthritis/arthropathy: OR,1.07), according to study results for the propensity score-matched pairs.

In secondary analyses, however, the association of statins with joint disease or osteoarthritis was statistically significant, the researchers reported, adding that a “wide array” of clinical presentation associated with use of the drugs included myalgias, muscle weakness, muscle cramps, rhabdomyolysis, autoimmune muscle disease and tendinous diseases.

“To our knowledge, this is the first study, using propensity score matching, to show that statin use is associated with an increased likelihood of diagnoses of musculoskeletal conditions, arthropathies and injuries,” the authors noted.

The authors posited several theories on why statin therapy could cause musculoskeletal adverse effects, including:

  • Statin therapy’s inhibitory effect on coenzyme Q10 synthesis9 selenoprotein synthesis and the mitochondrial respiratory chain;
  • The possible effect on apoptosis genes, which has been associated with myopathy in in vitro studies;
  • Evidence from pathologic studies that statin use might be associated with myopathy in the presence of normal creatine kinase levels, even in the absence of symptoms;
  • Research showing that statin-associated necrotizing autoimmune myopathy persisted or progressed, despite cessation; and
  • An increased incidence of tendinopathies in relationship to statin use, noted in multiple reports.

“Hence, it is conceivable that these effects may result in increased incidence of soft-tissue-related injuries, such as dislocation, sprain, and strain,” the authors wrote.

Statin Users Different

Among the 46,249 patients who met the study criteria before propensity matching, baseline characteristics were significantly different between those using statins and those who did not.

The statin group was older — mean age 60 compared to 45 in the nonuser group — more likely to be male and with more comorbidities such as history of heart attack, peripheral arterial disease, cerebrovascular disease and diabetes with complications. In addition, more of the users of cholesterol lowering drugs were obese smokers.

The majority of the patients on statin therapy were taking simvastatin (73.5%), followed by atorvastatin (17.4%), pravastatin (7%), rosuvastatin (1.7%), and fluvastatin or lovastatin (0.24%). More than one-third, about 34%, had been prescribed maximal doses, either 80 mg/day of simvastatin, atorvastatin, and pravastatin or 40 mg/day of rosuvastatin.

“The increased incidence of strain, sprain and dislocation with statin use has not been previously reported,” according to the authors, who noted that past studies have suggested a higher prevalence of statin-related muscle injury in physically active individuals. “The relationship between musculoskeletal injury and statin use deserves further study in a larger population because it carries a special relevance to our study population, which included active-duty soldiers.”

The ramifications go beyond the military, however, according to the report. The study’s conclusion suggested that “these findings are concerning because starting statin therapy at a young age for primary prevention of cardiovascular diseases has been widely advocated.”

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