Many of our patients have asked about the recent concerns about unusual femoral shaft (thigh bone) fractures seen in women taking bisphosphonates for osteoporosis. I came across this excellent article that covers many of these questions and concerns.

Article: Evolving Data about Subtrochanteric Fractures
and Bisphosphonates
Author: Elizabeth Shane, M.D.

Osteoporosis, a skeletal disorder characterized by reduced bone strength that predisposes to an increased risk of fracture, affects 10 to 12 million people in the United States. In 2000, there were 9 million fractures worldwide, of which 1.6 million were hip fractures. Fractures are important because of their association with an increased rate of death, substantial morbidity, enormous costs, and devastating effects on independence and quality of life.

Bisphosphonates such as Fosamax, Actonel and Boniva are the major class of drugs used to treat osteoporosis. They act by decreasing bone breakdown causing an overall increase in bone strength. They have been shown to reduce the risk of osteoporotic fracture in numerous large clinical trials. All these drugs reduce the rate of spine fractures, and reduce the rates of hip and nonspine fractures. Since Fosamax was approved in the United States in 1995, bisphosphonates have been used by millions of women and men worldwide.

In general, bisphosphonates have an excellent safety profile. However, a number of potential side effects have been identified. Among these are cases of "atypical" fracture of the femoral shaft that occur with minimal or no trauma. These fractures generally affect the upper third of the femoral shaft but may occur anywhere along the shaft. The majority of these case reports involved patients receiving long-term bisphosphonate therapy, sometimes together with other antiresorptive drugs, corticosteroids or proton-pump inhibitors. It has been suggested that in some patients prolonged administration of bisphosphonates may lead to oversuppression of bone turnover, which effectively makes the bones "old" and non supple.

However, it is important to recognize that these upper shaft fractures make up only 2 to 4% of all hip fractures. Atypical upper shaft fractures that are associated with bisphosphonate therapy are even less common. Epidemiologic studies suggest that femoral-shaft fractures are more likely to be caused by osteoporosis than by bisphosphonates and that the numbers of such fractures are reduced by high adherence to bisphosphonate therapy. The authors concluded that there was no significant association between bisphosphonate use and the risk of subtrochanteric or diaphyseal fracture, even among women who were treated for as long as 10 years. They calculated that treating 1000 women who had osteoporosis for 3 years would prevent about 100 fractures (including about 11 hip fractures), a benefit that exceeded the risk of subtrochanteric or diaphyseal fracture.

What are the implications of this study for clinical practice? The results provide assurance that subtrochanteric fractures are extremely rare, as compared with hip fractures. The findings also suggest that many more common and equally devastating hip fractures are prevented by bisphosphonates than are potentially caused by the drugs.

On the basis of available data, physicians should not rush to judgment and stop prescribing bisphosphonates because of concern about atypical femoral fractures. We must balance evidence of persistent antifracture efficacy after discontinuation with data showing that the use of alendronate for 10 years, as compared with 5 years, was associated with significantly fewer new vertebral fractures and nonvertebral fractures in patients with a bone mineral density T score of -2.5 or below.

Because femoral shaft fractures are so rare, many questions remain unanswered. The take home message is however bisphosphonates decrease fractures and save lives. If you have been on them for 5 years or more you may wish to talk to your doctor about taking a drug holiday.

Best regards,

Belinda Barclay-White, MD