Among patients treated with statins, the risk for osteoporosis may be dose-dependent, with osteoporosis underrepresented in low-dose and overrepresented in high-dose treatments, according to study results published in the Annals of the Rheumatic Diseases.

Researchers conducted a cross-sectional, retrospective analysis using data from Austrian patients with health claims to examine the relationship between statin type, statin dose, and osteoporosis diagnosis.

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Approximately 97% of the population had available health claims data, which included information on diagnoses from hospital stays and drug prescriptions with associated costs. Patients (n=7,945,775) were included in the study if they were alive during the entire observation period, from January 2006 to December 2007.

Overall, investigators assessed the data of 353,502 patients treated with statins (175,506 men and 177,996 women); 11,701 of these patients were diagnosed with osteoporosis (1765 men and 9936 women). The control group included 7,543,947 patients without exposure to statins, of whom 68,699 were diagnosed with osteoporosis (10,410 men and 58,289 women). Data from patients treated with statins were age- and sex-matched with nonstatin users in the cohort analysis.


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Researchers indicated that within the total study population, women were at a higher risk for osteoporosis compared with men (odds ratio [OR], 5.08; 95% CI, 4.98-5.18; P <.01). Osteoporosis was more common in patients of any age who were treated with statin therapies, compared with patients in the control group (OR, 3.62; 95% CI, 3.55-3.69; P <.01). A sex-based analysis found that osteoporosis diagnosis was overrepresented in both men and women treated with statins (OR [men], 3.35; 95% CI, 3.18-3.52; P <.01; OR [women], 3.90; 95% CI, 3.81-3.98; P <.01).

Patients were also stratified in 10-year intervals by age; the results of this analysis were similar. Osteoporosis remained overrepresented in patients treated with statins, with significantly stronger effects in women compared with men.  

Investigators noted that there was a “highly nontrivial dependence” between statin dosage and the odds of osteoporosis development. Among low-dose statin treatments (0-10 mg), osteoporosis was underrepresented in simvastatin, lovastatin, pravastatin, and rosuvastatin (ORs, 0.70, 0.39, 0.68, and 0.69, respectively). As statin dose increased, the relationship between dose and osteoporosis reversed, specifically in simvastatin, atorvastatin, and rosuvastatin.

In addition, investigators found that osteoporosis diagnosis was overrepresented in patients treated with >40 mg to 60 mg of simvastatin per day (OR, 1.64, 95 % CI, 1.31-2.07; P <.01), which increased with an increase in the daily dose of simvastatin >60 mg to 80 mg (OR, 3.30, 95% CI, 2.36-4.62; P <.01). A similar relationship was also noted in treatment with atorvastatin and rosuvastatin.

A logistic regression analysis was conducted, excluding patients with comorbidities including arthritis, cardiovascular disease, stroke, diabetes, renal failure, nicotine dependence, and diseases treated with corticosteroids. Exclusion of data from these patients did not change the initial results.

Study limitations included data extraction that could only identify a patient’s current statin dose, and the lack of confirmation of osteoporosis diagnosis because of the nature of data retrieval.

“We propose that monitoring patients [at high risk]…might be useful in order to offer an individual therapy to prevent or treat osteoporosis,” the researchers concluded. “Thus, larger and prospective studies with a focus on dosages of statins should be conducted in order to clarify the relationship with osteoporosis.”

Reference

Leutner M, Matzhold C, Bellach L, et al. Diagnosis of osteoporosis in statin-treated patients is dose-dependent [published online September 26, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215714