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

Abstract

BackgroundWhile 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.MethodsTo 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.ResultsThe 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.ConclusionsWe 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.

Peptidomimetic inhibitor of L-plastin reduces osteoclastic bone resorption in aging female mice

“… 33 While denosumab and bisphosphonates have been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture. 38 – 40 Romosozumab or anti-sclerostin monoclonal antibody reduced the risk of vertebral fractures, and it increased the bone mineral density of the lumbar spine. A significant reduction in bone resorption markers, increases in bone formation markers, and improved BMD in postmenopausal women, reducing the risk of clinical fracture.…”

Magnetic resonance imaging findings in the hyperacute phase of atypical femoral fracture: a case description

“…AFF is a fracture located along the femoral diaphysis between areas just distal to the lesser trochanter and just proximal to the supracondylar flare. AFF is associated with treatments using BMA including bisphosphonates or denosumab (1)(2)(3). Plain radiographs typically show a beak-or flare-like periosteal or endosteal callus in the lateral femoral cortex (4).…”

“…In the treatment of metastatic bone tumors, bone-modifying agents (BMA) including bisphosphonates and denosumab is known to reduce the frequency of skeletal-related event including severe bone-related pain, hypercalcemia, spinal cord compression, or pathological fracture (1)(2)(3). Whereas, atypical femoral fracture (AFF) has been reported as an adverse event following the treatments with BMA.…”

Evaluation of Pentosidine as Bone Quality Marker in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors

“…Fracture and osteoporosis are important adverse events in postmenopausal breast cancer patients receiving adjuvant AIs, and the prophylactic administration of BMA is recommended for patients with a high risk of bone-related adverse events [12,13]. Because long-term prescription of BMA can cause serious adverse events, such as osteonecrosis of the jaw and atypical femoral fracture in breast cancer, an appropriate evaluation of the risk of AI related fracture is desirable [14,15]. Although low BMD in femoral neck or lumbar spine is regarded as an independent risk factor for fracture, a certain proportion of patients with a non-osteoporotic range of BMD experience nontraumatic fractures [16,17].…”