Retrospective Review of Atypical Femoral Fracture in Metastatic Bone Disease Patients Receiving Denosumab Therapy

Yang, Samantha Peiling; Kim, Tae Won B.; Boland, Patrick J.; Farooki, Azeez

doi:10.1634/theoncologist.2016-0192

Cited by 43 publications

(42 citation statements)

References 33 publications

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“…During a median follow-up of 27 months, they identified one patient with a complete AFF (incidence 0.4%; 95% CI 0.1–2.2%) who received 70 doses of IV BP before receiving 28 monthly doses of denosumab [ 42 ]. They also reviewed all available radiographs in a subset of 66 patients with at least 21 monthly doses of denosumab; two patients had diffuse cortical thickening of the femoral diaphysis and localized periosteal reaction of lateral femoral cortex (incidence 4.5%; 95% CI 1.6–12.5%), confirmed on bone scan and magnetic resonance imaging [ 42 ]. These papers raise concern that clinical and subclinical presentations of AFF may be attributed to metastases and missed in cancer patients.…”

Section: Update On Epidemiologymentioning

confidence: 99%

Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures

Starr

Tay

Shane

2018

Curr Osteoporos Rep

114

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Purpose of ReviewTo summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF).Recent FindingsThe absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs. Lateral femoral bowing and varus hip geometry, which increase loading forces on the lateral femoral cortex, may increase AFF risk. Altered bone material properties associated with BP therapy may predispose to AFFs by permitting initiation and increasing propagation of micro-cracks. Relevant genetic mutations have been reported in patients with AFFs. Single X-ray absorptiometry femur scans permit early detection of incomplete and/or asymptomatic AFFs. Orthopedists recommend intramedullary rods for complete AFFs and for incomplete, radiologically advanced AFFs associated with pain and/or marrow edema on MRI. Teriparatide may advance AFF healing but few data support its efficacy.SummaryGreater understanding of biological and genetic predisposition to AFF may allow characterization of individual risk prior to initiating osteoporosis therapy and help allay fear in those at low risk for this complication, which remains rare in comparison to the osteoporotic fractures prevented by antiresorptive therapy.

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Section: Update On Epidemiologymentioning

confidence: 99%

Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures

Starr

Tay

Shane

2018

Curr Osteoporos Rep

114

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“…On the other hand, no AFF events were recorded in clinical trials of monthly denosumab (120 mg) treatment for patients with bone metastasis, despite the higher and more frequent dosing [6–12]. Although Yang, et al reported one case of clinical AFF in a patient receiving oncologic denosumab therapy from a retrospective review [22], clinical and pathological data are still lacking. We conducted this retrospective multi-center study to assess the incidence of AFF and the clinical and pathological features of patients with bone metastasis treated with denosumab at the dose of 120 mg monthly, and performed a systematic review of articles on this subject that we retrieved from a search of PubMed.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…Nonetheless, the use of denosumab is associated with two particular adverse reactions that, although rare, are of concern in this case. The first is an increased risk of atypical femur fractures mediated by a delay in bone remodelling especially with concomitant glucocorticosteroid use 15. The second is immune dysfunction and an increase in the incidence of infections, mediated by the inhibition of the RANKL/RANK expressed in monocytes and macrophages 14…”

Section: Discussionmentioning

confidence: 99%

Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis

2019

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Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5–10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13–1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30–100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient’s hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

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Retrospective Review of Atypical Femoral Fracture in Metastatic Bone Disease Patients Receiving Denosumab Therapy

Cited by 43 publications

References 33 publications

Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures

Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures

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

Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis

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