Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia

Abstract

Hypophosphatasia (HPP) is a rare and under-recognised genetic defect in bone mineralisation. Patients presenting with fragility fractures may be mistakenly diagnosed as having osteoporosis and prescribed antiresorptive therapy, a treatment which may increase fracture risk. Adult-onset HPPhypophosphatasia was identified in a 40-year-old woman who presented with bilateral atypical femoral fractures after 4 years of denosumab therapy. A low serum alkaline phosphatase (ALP) and increased serum vitamin B6 level signalled the diagnosis, which was later confirmed by identification of two recessive mutations of the ALPL gene. The patient was treated with teriparatide given the unavailability of ALP enzyme-replacement therapy (asfotase alfa). Fracture healing occurred, but impaired mobility persisted. HPP predisposes to atypical femoral fracture (AFF) during antiresorptive therapy; hence, bisphosphonates and denosumab are contraindicated in this condition. Screening patients with fracture or ‘osteoporosis’ to identify a low ALP level is recommended.