Reply to Letter to the Editor: The Effect of Long-term Alendronate Treatment on Cortical Thickness of the Proximal Femur

In recent years, atypical femoral fractures and osteonecrosis of the jaw have emerged as potential complications of long-term bisphosphonate therapy; osteonecrosis of the jaw has also been reported in patients receiving high doses of denosumab. The pathophysiology of both conditions is poorly defined, and the underlying mechanisms are likely to differ. The initiation of atypical fractures in the lateral femoral shaft suggests that reduced tensile strength, possibly secondary to alterations in the material properties of bone resulting from low bone turnover, may be an important pathogenetic factor. Osteonecrosis of the jaw is characterised by infection, inflammation, bone resorption and bone necrosis, but the sequence in which these occur has not been established. However, the observation that bone resorption occurs in close proximity to microbial structures suggests that infection may be the most important trigger, often as a result of dental disease. Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa.

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Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw

Compston

2011

Osteoporos Int

104

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Disentangling the Emerging Evidence around Atypical Fractures

Abrahamsen

Clark

2012

Curr Rheumatol Rep

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Atypical femur fractures are rare but a growing concern, as they are more common in patients who use bisphosphonates. The best radiology-based studies have had access to only short-term exposure data, while the studies using prescription databases with substantial long-term data did not have access to radiology reports. The interests of the patients are probably best served by reserving long-term bisphosphonate treatment for patients who are at the highest risk of osteoporotic fractures and considering drug holidays after 5 years in patients at low risk. Recent studies have further strengthened the case for active medical or surgical therapy in patients with incomplete fractures, but patient numbers are small, and randomized controlled trials may not be forthcoming in the immediate future. The recommendations made to establish an international database for such fractures have not yet been followed, and more epidemiologic and pathophysiologic research is needed.

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Reply to Letter to the Editor: The Effect of Long-term Alendronate Treatment on Cortical Thickness of the Proximal Femur

Cited by 2 publications

References 9 publications

Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw

Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw

Disentangling the Emerging Evidence around Atypical Fractures

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