Alendronate may reduce risk of hip fracture in older patients treated with prednisolone

EBM Focus - Volume 12, Issue 29

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Reference – JAMA 2017 Jul 11;318(2):146 (level 2 [mid-level] evidence)

  • Patients treated with corticosteroids are at an increased risk for bone fracture. Alendronate has been shown to reduce the risk of vertebral and hip fracture in patients with osteoporosis, as well as the risk of vertebral fracture in patients on corticosteroids. However, its effect on hip fracture in patients on corticosteroids is unknown.
  • The incidence of hip fracture was investigated in a retrospective cohort study of 3,604 patients (mean age 80 years, 70% female) taking average daily doses of prednisolone ≥ 5 mg for ≥ 3 months. A Swedish database was used to compare 1,802 patients who had alendronate after receiving oral prednisolone to 1,802 propensity score-matched patients who were taking prednisolone without alendronate.
  • The incidence of hip fracture was 9.5 per 1,000 person-years with alendronate vs. 27.2 per 1,000 person-years without alendronate (adjusted hazard ratio [HR] 0.35, 95% CI 0.22-0.54). Alendronate was also associated with a reduced risk of other fractures.

Patients treated with corticosteroids are at an increased risk for bone fracture (Osteoporos Int 2002 Oct;13(10):777, J Bone Miner Res 2004 Jun;19(6):893). Alendronate has been shown to decrease the risk of new vertebral fractures in a randomized trial of patients taking prednisone (Arthritis Rheum 2001 Jan;44(1):202). However, the effect of alendronate on the risk of hip fracture in patients on corticosteroids was previously unknown. This effect was recently investigated in a retrospective cohort study of 3,604 patients (mean age 80 years, 70% female) taking average daily doses of prednisolone ≥ 5 mg for ≥ 3 months. This cohort was derived from 433,195 adults registered in the Swedish Senior Alert database between 2008 and 2014. Patients were enrolled in the database in connection with a health care visit. There were 1,802 patients identified as receiving alendronate starting after the onset of prednisolone therapy, who had ≥ 3 months of alendronate treatment, and who were not taking other medication for osteoporosis. These 1,802 patients taking alendronate were compared to 1,802 propensity score-matched patients from a pool of 6,076 patients taking similar doses of prednisolone but not taking alendronate. The propensity score was calculated for each patient using anthropometric variables, clinical risk factors, and comorbidities. In the final cohort, about 87% in each group were taking calcium and vitamin D. The median follow-up was 1.3 years.

Alendronate was associated with a reduced risk of hip fracture (adjusted HR 0.35, 95% CI 0.22-0.54) with incident rates of 9.5 per 1,000 person-years with alendronate vs. 27.2 per 1,000 person-years without alendronate. Alendronate was also associated with a reduced risk of nonvertebral fracture (adjusted HR 0.55, 95% CI 0.43-0.71), major osteoporotic fracture (hip, wrist, shoulder, or clinical vertebral fracture) (adjusted HR 0.53, 95% CI 0.38-0.73), or any fracture (adjusted HR 0.58, 95% CI 0.46-0.73). There were no significant differences in mild upper gastrointestinal tract symptoms (dyspepsia, acid reflux, and esophagitis) or peptic ulcers.

This retrospective cohort study suggests that alendronate may reduce the risk of hip and other fractures in older patients taking prednisolone ≥ 5 mg daily for ≥ 3 months. Although recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis exist in different countries and the American College of Rheumatology (ACR) published recommendations as early as 1996 (Arthritis Care Res (Hoboken) 2017 Jun 6 early online), a systematic review of studies published between 1999 and 2013 from different countries indicates that the majority of patients receiving chronic glucocorticoids are not adequately managed to prevent osteoporosis (J Popul Ther Clin Pharmacol 2014;21(3):e486). Indeed, the current study shows that in the 7,878 patients taking prednisolone ≥ 5 mg/day for ≥ 3 months, 22.9% were treated with alendronate, and only about 47% of the 6,076 potential control patients for this study were treated with calcium and vitamin D. For the prevention and treatment of glucocorticoid-induced osteoporosis, the ACR recommends treating adults at low fracture risk with calcium and vitamin D, and for adults with moderate-to-high fracture risk, they recommend prescribing an osteoporosis medication (preferably an oral bisphosphonate) (Arthritis Care Res (Hoboken) 2017 Jun 6 early online). The evidence from this recent study supports the use of alendronate to decrease the risk of fracture in older patients taking an average daily dose of prednisolone ≥ 5 mg for at least 3 months.

For more information, see the Bisphosphonates for treatment and prevention of osteoporosis topic in DynaMed Plus. DynaMed users click here.


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