There has been evidence of association between femoral shaft fractures and prolonged bisphosphonate therapy. We present a case series of bisphosphonate-associated fractures and invaluable lessons we have learnt. Over the last three years at our unit we have collected a case series of eight patients who have had atypical femoral fractures whilst on bisphosphonate therapy. We present illustrative cases, a summary of key findings, and invaluable lessons we have learnt. There was a long period of prodromal pain for two years before incomplete fractures developed. We speculate this is a warning sign of impending fracture. This may have been prevented with screening. Between incomplete fracture and complete fracture there was a short window of one month. Five patients presented with complete fracture, and three with thigh pain +/- evidence of incomplete fracture. Of the latter group all but one went on to develop complete fractures. The one patient who did not progress died six years after diagnosis. Of those five patients who presented with initial complete fracture, three patients recall thigh pain before fracture on further questioning. Despite being diaphyseal femoral fractures, there is a higher risk of neck of femur fractures in this patient cohort (both patients with initial interlocked nails subsequently developed neck of femur fractures soon after and were revised to cephalomedullary nails). Excluding one death from unrelated cause, only one patient has signs of complete fracture healing. All other patients are still receiving follow-up (mean 490 days). Three patients reported bilateral symptoms (pain). Two had had bilateral symptoms for one year. Both had visible incomplete fractures on further radiographic scrutiny; one underwent prophylactic cephalomedullary nailing, one was managed with active surveillance. We suggest that improved pain and radiographic changes of cortical healing may be misleading and should not be relied upon. Cephalomedullary nailing is the treatment of choice in these fractures due to higher risk of neck of femur fractures in this cohort. We suggest prompt prophylactic cephalomedullary nailing when radiographic incomplete fractures are identified due to a short window before progression to complete fracture, and the need to consider contralateral prophylactic nailing in patients describing bilateral symptoms. We speculate that thigh pain is a warning sign of impending fracture and fracture-progression can be prevented with appropriate screening

Patients with cancer and bone metastases can have an increased risk of fracturing their femur. Treatment is based on the impending fracture risk: patients with a high fracture risk are considered for prophylactic surgery, whereas low fracture risk patients are treated conservatively with radiotherapy to decrease pain. Current clinical guidelines suggest to determine fracture risk based on axial cortical involvement of the lesion on conventional radiographs, but that appears to be difficult. Therefore, we developed a patient-specific finite element (FE) computer model that has shown to be able to predict fracture risk in an experimental setting and in patients. The goal of this study was to determine whether patient-specific finite element (FE) computer models are better at predicting fracture risk for femoral bone metastases compared to clinical assessments based on axial cortical involvement on conventional radiographs, as described in current clinical guidelines. 45 patients (50 affected femurs) affected with predominantly lytic bone metastases who were treated with palliative radiotherapy for pain were included. CT scans were made and patients were followed for six months to determine whether or not they fractured their femur. Non-linear isotropic FE models were created with the patient-specific geometry and bone density obtained from the CT scans. Subsequently, an axial load was simulated on the models mimicking stance. Failure loads normalized for bodyweight (BW) were calculated for each femur. High and low fracture risks were determined using a failure load of 7.5 × BW as a threshold. Experienced assessors measured axial cortical involvement on conventional radiographs. Following clinical guidelines, patients with lesions larger than 30 mm were identified as having a high fracture risk. FE predictions were compared to clinical assessments by means of diagnostic accuracy values (sensitivity, specificity and positive (PPV) and negative predictive values (NPV)). Seven femurs (14%) fractured during follow-up. Median time to fracture was 8 weeks. FE models were better at predicting fracture risk in comparison to clinical assessments based on axial cortical involvement (sensitivity 100% vs. 86%, specificity 74% vs. 42%, PPV 39% vs. 19%, and NPV 100% vs. 95%, for the FE computer model vs. axial cortical involvement, respectively). We concluded that patient-specific FE computer models improve fracture risk predictions of femoral bone metastases in advanced cancer patients compared to clinical assessments based on axial cortical involvement, which is currently used in clinical guidelines. Therefore, we are initiating a pilot for clinical implementation of the FE model