Atypical Fractures in Long-Term Bisphosphonate Users

[Dr.Wala'a 4]

Tuesday, December 15, 2009

Atypical Fractures in Long-Term Bisphosphonate Users

A small subgroup of women might be susceptible.


Although bisphosphonates lower overall risk for fractures in women with osteoporosis, an unusual type of femoral fracture has been described in a few long-term bisphosphonate users (see accompanying image down). Two reports provide additional information.

In a case series, orthopedists at New York University describe seven women on long-term alendronate therapy (average duration, 9 years) who sustained sequential or simultaneous bilateral femoral "low-energy" fractures (i.e., resulting from falls from standing height or lower). All fractures were subtrochanteric or involved the femoral shaft, unlike typical femoral fractures that involve the intertrochanteric or femoral neck regions. These fractures each had a unique appearance, with a spike or beak configuration and cortical thickening at the fracture site.

In a case-control study from Cornell University, 41 postmenopausal women with low-energy subtrochanteric or femoral-shaft fractures were compared with 82 control women with classic intertrochanteric or femoral-neck fractures. Case patients were significantly more likely to be taking bisphosphonates than were controls (37% vs. 11%). Moreover, among case patients, the fracture pattern of "beaking with thick cortex" was highly correlated with prolonged bisphosphonate use (mean, 7 years).

Comment: These reports, and several others, suggest that a small subgroup of women could be susceptible to atypical femoral fractures after prolonged bisphosphonate use; suppression of bone turnover and accumulation of microdamage is a postulated mechanism. Prospective studies are needed to prove a causal relation; if causality is demonstrated, we'll need to determine whether the incidence of this complication is appreciable and whether at-risk patients can be identified.


— Allan S. Brett, MD
Published in Journal Watch General Medicine December 15, 2009

the picture

[Dr.Wala'a 4]

one of the old reports

April 5, 2005

Is Long-Term Bisphosphonate Therapy Safe?

In a case series, long-term alendronate use was associated with reduced rates of bone formation and inadequate fracture healing.

Bisphosphonates (alendronate [Fosamax] and others) inhibit bone resorption and reduce the incidence of fractures in osteoporotic patients during several years of use. However, these drugs theoretically might weaken bone in the longer term (e.g., by inhibiting normal repair of bone "microdamage" that occurs in daily life).

These researchers evaluated nine patients who sustained nontraumatic nonspinal fractures (e.g., of the femur or pelvis) after 3 to 8 years of alendronate therapy. Three patients also used estrogen, and two took glucocorticoids. Bone biopsies with labeling studies revealed severe reductions in bone formation rates in all patients compared with previously published rates in healthy postmenopausal women. Eight to 12 months after discontinuation of alendronate, fracture healing was inadequate in four patients.

Comment: This provocative report suggests that, in some patients, long-term bisphosphonate therapy may be associated with weakened bone and increased susceptibility to fractures. Obviously, this uncontrolled case series cannot establish cause and effect, but it does signal a need for closer attention to this potential problem. According to a recent study, the safety and effectiveness of alendronate persisted during 10 years of use, but that study was not designed to detect increased susceptibility to fractures in subgroups of long-term alendronate users (Journal Watch Apr 2 2004). An editorialist suggests that bisphosphonate therapy in osteoporotic patients should be stopped after 5 years, pending additional research to clarify the risks and benefits of long-term therapy.

— Allan S. Brett, MD
Published in Journal Watch General Medicine April 5, 2005

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