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High-dose statin therapy may heighten fracture risk
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Individuals prescribed high-dose statin therapy to manage cardiovascular risk are more likely to receive a diagnosis of osteoporosis compared with those prescribed a low-dose statin or no therapy, according to findings from a database analysis published in Annals of Rheumatic Diseases.
“Nowadays, we have the evidence-based dogma ‘the lower the better’ for cholesterol in regard to prevention of cardiovascular outcomes,” Alexandra Kautzky-Willer, MD, professor in the division of endocrinology and metabolism at the Medical University of Vienna, told Endocrine Today. “However, there could be neglected side effects related to high doses of statins. We looked at possible associations between statins and bone health. Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose statin treatment and overrepresented in high-dose statin treatment.”
Assessing statin use
In a cross-sectional, retrospective study, Kautzky-Willer and colleagues analyzed data from all Austrians with health claims alive during the 2006-2007 observation period to identify individuals treated with statins (n = 7,897,449; 4,194,877 women). Researchers identified all individuals with at least one prescription of any of the seven statins available on the market during the observation period — simvastatin, lovastatin, pravastatin,
fluvastatin, atorvastatin, cerivastatin (Baycol, Bayer) and rosuvastatin — and assessed defined daily dose averages. The average daily dose was calculated as the amount of the drug (converted from defined daily dose to milligram) divided by the number of treatment days that the patient did not spend in a hospital. Patients were then stratified by average daily dose for each statin (0-10 mg; > 10-20 mg; > 20-40 mg; > 40-60 mg; and > 60-80 mg). Researchers applied multiple logistic regression to analyze dose-dependent risks for an osteoporosis diagnosis for each statin individually, stratified by age and sex.
Within the cohort, researchers identified 353,502 statin-treated patients (177,996 women), with 11,701 such patients (9,936 women) were diagnosed with osteoporosis. The control group (no statin exposure) consisted of 7,543,947 patients (4,016,881 women), including 68,699 patients (58,289 women) diagnosed with osteoporosis.
Researchers found that statin treatment was associated with an overrepresentation of diagnosed osteoporosis in the overall population when compared with controls (OR = 3.62; 95% CI, 3.55-3.69), noting there was a “highly non-trivial dependence” of statin dosage with the ORs for osteoporosis.
Osteoporosis was underrepresented in low-dose statin treatment, defined as 0 mg to 10 mg per day, for lovastatin (OR = 0.39; 95% CI, 0.18-0.84), pravastatin (OR = 0.68; 95% CI, 0.52-0.89), simvastatin (OR = 0.7; 95% CI, 0.56-0.86) and rosuvastatin (OR = 0.69; 95% CI, 0.55-0.87). However, researchers noted that the relationship between statin treatment and osteoporosis reverses with increased dosages. Compared with individuals not prescribed statin therapy, those prescribed simvastatin exceeding the 40 mg threshold were 64% more likely to receive an osteoporosis diagnosis (OR = 1.64; 95% CI, 1.31-2.07), and individuals prescribed atorvastatin therapy exceeding the 20 mg threshold were 78% more likely to receive an osteoporosis diagnosis (OR = 1.78; 95% CI, 1.41-2.23). Those prescribed rosuvastatin exceeding 20 mg were twice as likely to receive an osteoporosis diagnosis vs. controls (OR = 2.04; 95% CI, 1.31-3.18). Patient numbers were too low to reliably estimate dosage-dependence for the remaining types of statins, according to researchers.
Consider dose, risk
“In clinical practice, high-risk patients for osteoporosis under high-dose statin treatment should be monitored more frequently regarding bone health,” Kautzky-Willer said. “We propose that monitoring high-risk patients, such as postmenopausal female patients under high-dosage statin therapy, may help to offer an individual therapy to prevent or treat osteoporosis. Personalized medicine should consider individual risks and doses and possible differences within the class of drugs.”
Kautzky-Willer said future studies must take dose-dependency into account when investigating the relationship between statins and osteoporosis. “Larger and prospective studies with a focus on dosages of statins should be conducted in order to clarify the relationship with osteoporosis,” Kautzky-Willer said. “We are planning a prospective study investigating bone health and sex hormones in men and women following statin therapy.” – by Regina Schaffer
For more information:
Alexandra Kautzky-Willer, MD, can be reached at Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna 1090, Austria; email: Alexandra.kautzky-willer@meduniwein.ac.at.
Disclosures: The authors report no relevant financial disclosures.
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