Atypical femoral fracture after receiving antiresorptive drugs in breast cancer patients with bone metastasis

Abstract

BackgroundAtypical femoral fracture (AFF) occurs with minor trauma in patients receiving antiresorptive drugs such as bisphosphonate and denosumab. We hypothesized that patients with bone metastasis who receive higher doses of antiresorptive drugs tend to experience AFF more frequently. This study aimed to investigate the prevalence rate of AFF in patients receiving antiresorptive drugs for bone metastasis of breast cancer.MethodsBased on the database from our hospital, patients with breast cancer between March and September 2014 were investigated. Thirty-two patients with bone metastasis who received higher doses of antiresorptive drugs were included for analysis and defined as the metastasis (M) group. For the control (C) group, 32 patients in the same period with breast cancer without bone metastasis who did not undergo antiresorptive drug therapy were included. We evaluated the localized periosteal thickening of the lateral cortex (beaking) and femoral neck-shaft angle in CT scout view, the periods from induction of antiresorptive drugs to the appearance of beaking, and the occurrence rate of complete fracture. The 2 groups were compared.ResultsOf the 64 limbs in 32 patients of the M group, 8 limbs in 6 patients showed beaking at the subtrochanteric area (12.5%). After the occurrence of beaking, 5 limbs in 3 patients eventually had a complete fracture with minor trauma (7.8%). On the other hand, no beaking was observed in the C group.ConclusionsThe frequency of AFF in patients with breast cancer receiving bisphosphonate and/or denosumab for bone metastasis was high. More attention should be paid to the occurrence of AFF in these patients than osteoporotic patients.

Periosteal progenitors contribute to load-induced bone formation in adult mice and require primary cilia to sense mechanical stimulation

“…Conversely, a lack of physical loading causes osteocytes to trigger osteoclastic bone resorption, adapting the skeleton to reduce weight and metabolic demands while maintaining sufficient strength to withstand the reduced loads. Treatments that prevent resorption to combat bone loss have been associated with atypical fracture [ 2 , 3 ]. Thus, the focus has shifted towards strategies favoring bone anabolism.…”

The enigma of atypical femoral fractures

“… 22 Since the application of antiresorptive drugs in these patients is also employed in long-term settings, this phenomenon is expected to become more and more apparent and common. 23 Furthermore, in a Phase III multicentre, randomized, double-blind, placebo-controlled trial, reporting data for 10-year treatment with denosumab in postmenopausal women with osteoporosis, two cases of atypical femoral fractures were identified. 24 In summary, other pharmacological treatments which decrease bone turnover apparently have the same consequences regarding the risk for this special fracture type.…”

The limitations of today’s clinical guidance: Atypical femoral fracture and long-term bone-modifying agents in the oncology setting

“…27 As a relatively uncommon phenomenon, real-world AFF cases may go unrecognized, and retrospective cohort studies have indeed found subclinical stress reactions and undiagnosed clinical AFF. 20,28 Impending AFF may also be misinterpreted as bone metastases, and corresponding treatment with bone radiation can substantially weaken the area. Importantly, cortical bone metastases are rare 20 and should raise suspicion for AFF.…”

“…17 For bone metastases, evidence of beaking was apparent at an average onset of 48.4 months of BMA use in a matched cohort study. 28 This suggests that screening for radiographic signs of AFF by 4 years may be prudent, especially if the patient already undergoes routine imaging for oncologic or other indications. However, there is no standard surveillance guidance to evaluate the development of beaking or cortical changes for patients on prolonged therapy.…”