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You are here: Home / New investigators / Newsletter / Webinar series “Bone, Muscle & Beyond”: Atypical femur fractures. By Cristiana Cipriani

Webinar series “Bone, Muscle & Beyond”: Atypical femur fractures. By Cristiana Cipriani

The webinar held by Dr Carola Zillikens on July 21st, whose recording is available online on the dedicated page of the ECTS website, discussed a rare but important topic in the management of patients with osteoporosis, namely atypical femur fractures (AFF). Whether you did not have the possibility to participate, or just would like to recall the most important data from the literature on genetics and therapeutic management of AFF, here we report the most relevant points covered by Dr Zillikens.

AFF are rare spontaneous fractures of thigh bone, which are considered to be adverse event of long-term use of antiresorptive drugs, even though the cause is still not clear. It is important for clinicians to recall which patients may be at higher risk of AFF: those on chronic corticosteroid therapy, multimorbid patients, some ethnicities (Asian), and those with genetic predisposition. The idea that genetic factors play a key role in the pathogenesis of AFF comes from the clinical observation of the occurrence of such fractures in bisphosphonates-naïve patients, in families, specific ethnicity (Asian), as well as in monogenic bone disease. A recent systematic review published by the group of Dr Zillikens reported interesting data in this context by analyzing 57 cases of AFF and monogenic bone disorders (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016774/). In particular, authors showed that 23 patients with AFF were finally diagnosed with hypophosphatasia by the presence of the ALPL mutation; 20 were diagnosed with osteogenesis imperfecta and others with metabolic bone disorders causing defect in mineralization, remodeling, collagen synthesis, and osteocyte function. Interestingly, 56% of AFF cases did not have history of exposure to bisphosphonates. Family and genetic studies showed that mutation in genes associated with the mevalonate pathway, as well as in drug metabolism, response to bisphosphonates, and abnormal bone mineralization may be associated with higher risk of AFF. An important point for future studies to be carried out in larger cohorts is the interplay between these genetic variants and bisphosphonates use in the pathogenesis of AFF. Additionally, the role of biomechanical and interacting factors needs to be fully addressed.

With reference to treatment, Dr Zillikens underlined that it is challenging to define how to manage patients on prior antiresorptive therapy reporting AFF. Indeed, patients with osteoporosis developing AFF often still need therapy for osteoporosis. The practice guidelines from the ECTS (https://pubmed.ncbi.nlm.nih.gov/31867670/) advise to estimate the risk of fragility fractures in these patients, stop bisphosphonates or denosumab, and monitor fracture healing and/or development of new AFF with upper legs imaging in the first 1-2 years. In high-risk patients, the authors recommend the use of teriparatide or abaloparatide for 1-2 years; romosozumab or raloxifene could be considered if teriparatide is not an option. After teriparatide, denosumab, bisphosphonates or raloxifene should be considered in high-risk patients. In case of low bone turnover, no therapy should be the option, and bone turnover markers and BMD should be monitored. In patients with low fracture risk, a short course of bisphosphonates after denosumab discontinuation should be considered, while there is no absolute indication for teriparatide.

To watch the video please go to https://ectsoc.org/event/bmb-july2022/ and login with your username and password.

Enjoy!

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