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Multicenter Study
. 2019 Oct 22;19(1):980.
doi: 10.1186/s12885-019-6236-6.

Atypical femoral fracture in patients with bone metastasis receiving denosumab therapy: a retrospective study and systematic review

Momoko Takahashi  1 , Yukinori Ozaki  2 , Rika Kizawa  3 , Jun Masuda  3 , Kentaro Sakamaki  4 , Keiichi Kinowaki  5 , Taro Umezu  6 , Chihiro Kondoh  3 , Yuko Tanabe  3 , Nobuko Tamura  7 , Yuji Miura  3 , Takashi Shigekawa  8 , Hidetaka Kawabata  7 , Noriyuki Baba  8 , Haruo Iguchi  9 , Toshimi Takano  3
Affiliations
Multicenter Study

Atypical femoral fracture in patients with bone metastasis receiving denosumab therapy: a retrospective study and systematic review

Momoko Takahashi et al. BMC Cancer. .

Abstract

Background: While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy.

Methods: To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions.

Results: The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF.

Conclusions: We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.

Keywords: Bone metastasis; Denosumab; Femoral fractures; Retrospective studiess; Systematic review.

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Conflict of interest statement

Toshimi Takano has competing interest with Daiichi-Sankyo, Kyowa Hakko Kirin, and Eisai. Other members have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Radiological findings of atypical femoral fracture. a X-ray images of Case 1. White arrow shows atypical femoral stress reaction (AFSR) on the right femur. X-ray of the left femur at the time of the AFF event and after intramedullary nail surgery. b X-ray images of Case 2. White arrow shows AFSR in the left femur. c X-ray and PET/CT images of Case 3. The upper images show bilateral AFSR and the middle image shows no metastasis in either femur. The lower images are x-rays obtained after prophylactic intramedullary nail fixation surgery. d X-ray images of Case 4. The upper images show left AFF and right AFSR. The lower images are X-rays after intramedullary nail fixation surgery on both sides. e X-ray, MRI and PET/CT images of Case 5. The upper left image is an x-ray showing left AFSR and upper right image is an MR image of the same region. The lower left image is a PET/CT image showing no evidence of malignancy and the lower right image is hematoxylin and eosin staining of fracture tissue from Case 5 (× 400). The section shows fragmented bone tissue, fibrous tissue, calcification, and a little bone marrow tissue
Fig. 2
Fig. 2
Cumulative frequency curve of atypical femoral fracture events in patients with bone metastasis receiving denosumab 120 mg monthly
Fig. 3
Fig. 3
Flow diagram of the literature search and study selection process
See this image and copyright information in PMC

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