Alendronate

Oral prednisolone is used to alleviate symptoms of inflammatory diseases, but its diminishing effect on bone density leaves patients prone to fractures. Anti-osteoporotic medication alendronate is thus being investigated as an antidote to prednisolone’s bone depleting effects.

Although commonly used to treat inflammation, glucocorticoid use may lead to secondary osteoporosis. Glucocorticoids, which are a type of steroid hormone, cause bone density to diminish, increasing the risk of fractures of the hip by 60% and the vertebrae by 160%. The treatment is common for seniors aged 65 and over, and studies have shown its use increases the risk of hip fractures by a magnitude of 2.1 in 80-year-old patients. Alendronate, a drug used to treat osteoporosis, has been shown to prevent vertebral fractures in patients using glucocorticoids and results in a 40% risk reduction of hip fractures in postmenopausal women not taking glucocorticoids. As hip fractures have a great impact on physical function, mobility, morbidity, and mortality, studies are needed to investigate alendronate’s effect on such fractures in patients taking glucocorticoids.

In a retrospective study by Axelsson and colleagues, published in the Journal of the American Medical Association, investigators analyzed the 2005-2014 health data of patients aged 65 and older who were on oral prednisolone, a common glucocorticoid, to determine if alendronate use reduced their risk of fractures. All patients in the study were selected from the Swedish Senior Alert Database from 2008-2014, but as it monitors developments in senior preventive care, their medication data were obtained from before their registration in the database. Using the Swedish Prescribed Drug Register to examine medication data, investigators chose patients who were being treated with at least 5 mg per day of prednisolone for at least 3 months and had not been treated with other osteoporotic medicines or been on alendronate in the past. Other national registers were used alongside the aforementioned database and register to compile fall and fracture information about the patients. The primary outcome was hip fractures and to qualify as such, a fracture of the femoral head, neck, trochanter or subtrochanter had to occur. Other outcomes included falls without fractures, death, non-vertebral fractures and other major osteoporotic fractures.

Of the initial cohort of 433,195 patients, the investigators included 3604 individuals, 1802 who were on prednisolone and alendronate and 1802 who received prednisolone treatment only were matched as controls. In patients using concurrent prednisolone and alendronate, 27 hip fractures occurred while 73 occurred in those using prednisolone alone. This effect of alendronate on preventing hip fractures was seen whether patients had medium or high doses of prednisolone and all secondary outcomes were reduced in patients using alendronate. With increased adherence and duration of treatment with alendronate, the risk of hip fractures was reduced.

Overall, patients taking alendronate while being treated with medium or high doses of prednisolone for a median time of 2.9 years showed a decrease in the risk of hip fractures. The large initial number of patients selected allowed for diverse and balanced control group selection but the low number of hip fractures, lack of bone density information, primarily white population and observational nature of the study are all limitations of the study. Despite these limitations, this important study revealed alendronate’s preventive effect on hip fractures in patients using prednisolone.

Written by Monica Naatey-Ahumah, BSc

References

Axelsson, K.F., Nilsson, A.G., Wedel, H., Lundh, D., and Lorentzon, M. (2017). Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone. JAMA, 318(2), 146-155.

Miller, W.L. (1988). Molecular Biology of Steroid Hormone Synthesis. Endocr Rev, 9(3), 295-318.

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