Bisphosphonate Use and Risk of Atypical Fractures in Women

Park-Wyllie, et al.   Bisphosphonate Use and Risk of Subtrochanteric or Femoral Shaft Fractures in Older Women,  JAMA 305:783-789, 2011

Osteoporosis is associated with significant morbidity and mortality.  Oral bisphosphonates have become a mainstay of treatment, but concerns have emerged that long term use of these drugs may suppress bone remodeling, leading to unusual fractures.  The current study was designed to determine whether prolonged use was associated with an increased risk of subtrochanteric or femoral shaft fractures.  The study population with from Ontario Canada and consisted of women aged 68 years or older.  Nearly 53,000 women were studied with at least five years of bisphosphonate therapy.  The fractured occurred in 117 (0.22%) with an odd ratio of 2.74 (1.25-6.02) making this a statistically significant risk.  It should be noted that the patients who took bisphosphonate for less than five years did not have any statistical risk for these fractures.

This study also looked at the risk of femoral neck and intertrochanteric hip fractures.  These fractures were statistically significantly less likely to happen in the patients taking bisphosphonate (odds ratio 0.76 (0.63-0.93)).

Dr. Albrecht’s commentary: Bisphosphonate has become a very common treatment for postmenopausal women with osteoporosis to help prevent the risk of fractures.  It is important however to realize that medicine as well as in life there is “no free lunch.”  This is yet another study showing that medicines can have adverse impact as well as beneficial effects.

This study represents the largest assessment of the potential fracture complications of bisphosphonate to date.  It is interesting to note that the reduction in the typical hip fractures (fractures of the femoral neck and intertrochanteric location) was not seen in patients who had taken the bisphosphonate for less than three years.  The benefits were greater in patients who were on bisphosphonate for more than five years.  It should also be noted that there were 10-15 times more typical hip fractures than the unusual hip fracture of the sub trochanteric and femoral shaft location.  However, to get the most benefit of your bisphosphonate therapy you need to take it for five years or more which is the same time interval that increases the risk of the abnormal fractures.  It should be noted that taking bisphosphonate for five years or more will cause 1 abnormal fracture for every 4 typical hip fractures it will prevent.  Are these good odds?  From a statistician’s point of view and medical practice in general, yes.  But not if you are the one with the abnormal fracture.  I also want to point out that bisphosphonates have been shown to reduce the risk of osteoporotic fractures at other sites including the wrist and spine.

Information that is not available in this study is the status of the bone density testing and all of the patients.  Did they all have osteoporosis?  Many physicians are now beginning to treat osteopenia with bisphosphonate.  Do patients with osteoporosis have a more favorable risk ratio of typical to abnormal hip fractures when taking bisphosphonates?  Osteopenia patients are less likely to reduce their risk of typical hip fractures with bisphosphonate therapy, but are they just as likely to develop the abnormal hip fractures on bisphosphonate therapy?

Perhaps the big question is which patients are ideal candidate for a therapy.  Perhaps we are learning that the benefit risk ratio for patients with osteopenia is too low but there definitely is benefit in patients with osteoporosis.

This article and commentary dovetail with the article reviewed several months ago regarding the risk of calcium therapy.  In the past we thought that calcium was highly beneficial for osteoporosis but we are now finding that there is an increased risk of cardiovascular disease for some patients.  Again “no free lunch.”  Perhaps we need to be thinking about alternative therapies for osteoporosis for most of our patients.  As outlined in that commentary, vitamin D and strontium may be excellent options for the prevention of osteoporosis.  These supplements along with bisphosphonates may be valuable for the treatment of osteoporosis, and if density testing shows good improvement in bone density, it may be valuable to discontinue the bisphosphonate.  This “drug holiday” may help reduce the risk of abnormal hip fractures.