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Oral bisphosphonate therapy reduces fracture risk in glucocorticoid users

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October 30, 2017

Among patients treated with oral glucocorticoid therapy, alendronate and risedronate reduced the 1-year risk for hip fracture, and alendronate, risedronate and etidronate reduced vertebral fracture risk, according to findings reported in the Journal of Bone and Mineral Research.

Oral glucocorticoid exposure is the most common cause of secondary osteoporosis, and fracture risk rapidly increases in the first year after glucocorticoid exposure in a dose-dependent manner, Mohamed Amine Amiche, MSc, PhD, of the Leslie Dan Faculty of Pharmacy at the University of Toronto, and colleagues wrote in the study background. Fracture prevention is indicated for all oral glucocorticoid users who are expected to take a minimum of 7.5 mg prednisone equivalent for at least 3 months, they noted.

“Bisphosphonates are the first-line therapy for [glucocorticoid]-induced osteoporosis, yet efficacy has only been established in primary osteoporosis, and the benefit of bisphosphonate treatment remains controversial; particularly since the mechanism of action of bone loss seen with [glucocorticoid] use differs from primary osteoporosis,” the researchers wrote. “To date, no trials have used fracture as the primary endpoint in [glucocorticoid]-induced osteoporosis, and thus anti-fracture efficacy is lacking.”

Amiche and colleagues analyzed data from 18,234 adults aged at least 66 years who initiated oral glucocorticoid therapy in Ontario between 1998 and September 2014, using information from the Institute for Clinical Evaluative Sciences, which includes inpatient, outpatient and demographic data (mean age, 76 years; 63% women). Chronic oral glucocorticoid therapy was defined as at least two oral glucocorticoid prescriptions and a cumulative exposure of at least 450-mg prednisone equivalent in a 6-month window. Researchers stratified the cohort into three prescription groups: alendronate (n = 3,945), etidronate (n = 8,464) and risedronate (n = 5,825). Each subgroup was matched to unexposed patients. Researchers assessed hip, vertebral, forearm (radius or ulna) and humerus fractures; hip fracture was the primacy outcome.

Comparing exposed and unexposed subgroups, the crude event rate per 1,000 person-years for hip fracture was 5.2 vs. 9.9 for alendronate, 9.6 vs. 11 for etidronate and 5.5 vs. 9.5 for risedronate.

Researchers found that alendronate reduced hip fracture (HR = 0.46; 95% CI, 0.25-0.8) and vertebral fracture risk (HR = 0.52; 95% CI, 0.39-0.68). Risedronate was also associated with a reduction in both hip fracture (HR = 0.58; 95% CI, 0.36-0.9) and vertebral fracture risk (HR = 0.47; 95% CI, 0.36-0.6); however, etidronate was associated with a reduction in vertebral fracture only (HR = 0.59; 95% CI, 0.48-0.73), according to researchers.

Altogether, oral bisphosphonates were associated with a reduction in hip fracture (HR = 0.71; 95% CI, 0.57-0.89) and vertebral fracture risk (HR = 0.58; 95% CI, 0.51-0.66).

None of the included bisphosphonates was associated with a reduction in forearm or humerus fracture risk, according to researchers.

“We hope that our results will help to improve the management of [glucocorticoid]-induced osteoporosis by providing real-world evidence of the benefit of alendronate and risedronate in preventing [glucocorticoid]-associated fractures,” the researchers wrote, adding that future studies should examine the comparative effectiveness of oral bisphosphonates among oral glucocorticoid users, as well as their effectiveness compared with newer agents with less frequent dosing interval, such as zoledronic acid and denosumab (Prolia, Amgen). – by Regina Schaffer

Disclosures: One of the study authors reports he has participated in clinical trials sponsored by Amgen, Merck, Novartis and Procter & Gamble for the prevention and treatment of glucocorticoid-induced osteoporosis, and has received consultant fees and research grants from Actavis, Amgen, Eli Lilly, Merck and Novartis.