Alendronate Cuts Hip-Fracture Rates in High-Risk Elderly

Pam Harrison

July 11, 2017

Prophylactic use of alendronate in elderly patients requiring oral prednisolone for whatever condition dramatically reduces the risk of hip fracture, at least in the short term, a new retrospective cohort study suggests.

"Alendronate has been shown to improve bone-mineral density and reduce the risk of vertebral fractures in patients treated with glucocorticoids," senior author Mattias Lorentzon, MD, PhD, head of geriatric medicine, Sahlgrenska University Hospital in Molndal, Sweden, told Medscape Medical News in an email.

"But our study is the first to provide evidence supporting [the idea] that alendronate also protects against the most severe fracture, namely hip fracture, so I think it's clear that results from our study support the use of alendronate in older patients taking prednisolone," he added.

The study was published in the July 11 issue of the Journal of the American Medical Association, by Kristian Axelsson, MD, Sahlgrenska University Hospital, and colleagues.

Alendronate Protected Against Fracture Risk From All Doses of Steroid

Men and women 65 years of age and older who were enrolled in the Senior Alert database between 2008 and 2014 were available for inclusion in this study.

"Only patients who had not previously taken alendronate and [who] started alendronate treatment after prednisolone treatment were included," the researchers note.

A total of 3604 patients, mean age 79.9 years, were included in the analysis — 1802 of them having been prescribed alendronate after having been prescribed oral prednisolone at a dose of at least 5 mg a day for at least 3 months.

They were matched with 1802 control patients who received oral prednisolone unaccompanied by alendronate.

Patients taking any other medications for osteoporosis were excluded.

Seventy percent of the cohort was female and the median time patients had been on alendronate was 2.9 years.

At a median follow-up of only 1.32 years, investigators documented 27 hip fractures in patients taking concomitant alendronate vs 73 hip fractures in the prednisolone-alone group, for a 65% relative risk reduction in the risk of hip fracture in favor of the alendronate group.

This corresponded to an incidence rate of 9.5 hip fractures per 1000 person-years for the alendronate treatment group compared with an incidence rate of 27.2 hip fractures per 1000 person-years, Dr Axelsson told Medscape Medical News  in an mail.

At 30 months, the absolute reduction in risk of hip fracture was estimated to be 4.1% in favor of those treated with additional alendronate, which was statistically significant in women but which lacked statistical power among men.

Protection against hip fracture with concomitant use of alendronate was observed in patients taking both medium and high doses of prednisolone (>5 mg).

All Fracture Risk Reduced

"For patients using prednisolone, the risk of major osteoporotic fracture, any fracture, and nonvertebral fractures was significantly lower in patients treated with alendronate than in those not treated with it," the investigators observe.

Multivariable-Adjusted Hazard Ratio (HR) for Fracture Risk Over Follow-up

Group Major osteoporotic fracture, HR (P) Any fracture, HR (P) Nonvertebral fracture, HR (P)
Prednisolone only 1 (Reference) 1 (Reference) 1 (Reference)
Alendronate treated 0.53 (<.001) 0.58 (<.001) 0.55 (<.001)

Patients treated with additional alendronate also had a 12% lower risk of mortality at a HR of 0.88 at the end of follow-up, although death from hip fracture itself did not differ significantly between the two groups.

The investigators do concede that the observational design of the study was a limiting factor, as was the small number of fracture events.

Adverse events including mild upper-gastrointestinal-tract symptoms or peptic ulcers were not significantly different among the two groups, say the researchers.

They also observed no instances of bisphosphonate-induced osteonecrosis, and only one case of femoral shaft fracture occurred in each of the two groups.

Asked if longer duration of alendronate treatment might be expected to further reduce hip-fracture risk, Dr Lorentzon felt it was difficult to speculate whether prolonged follow-up would change the observed association.

"However, I believe that the potential protective effect of alendronate would already [have been]…present for most patients upon entering the study," he observed.

The fact that the observed 65% relative risk reduction in hip fracture in this study far exceeded the general reduction in fracture risk reported from randomized trials in postmenopausal osteoporosis is not all that surprising, he added.

"These results support the use of alendronate in this patient group," he and his colleagues conclude.

This is because these patients were at particularly high risk for fracture due to their advanced age and the relatively high doses of glucocorticoids used in the study.

The authors had no relevant financial relationships.  

JAMA. 2017;318:146-155. Abstract

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