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Title: Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia.
Austin Authors: Warren, Annabelle M;Ebeling, Peter R;Grill, Vivian;Seeman, Ego ;Sztal-Mazer, Shoshana
Affiliation: Women's Health Research Program, School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia
Department of Endocrinology, Monash Health, Clayton, Victoria, Australia
Department of Endocrinology, Western Health, St Alban's, Victoria, Australia
Department of Endocrinology, The Alfred Hospital, Melbourne, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Issue Date: 1-Sep-2021
Date: 2021-09-01
Publication information: Endocrinology, Diabetes & Metabolism Case Reports 2021; online first: 1 September
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. Hypophosphatasia (HPP) is a rare and under-recognised cause of bone fragility produced by impaired matrix mineralisation that can be misdiagnosed as a fragility fracture due to age-related bone loss. Antiresorptive therapy is contraindicated in HPP. Low serum alkaline phosphatase (ALP) provides a clue to the diagnosis. Elevated serum vitamin B6 (an ALP substrate) is indicative of HPP, while identification of a mutation in the ALPL gene is confirmatory. Enzyme therapy with recombinant ALP (asfotase alfa) is currently prohibitively costly. Treatment with anabolic bone agents such as teriparatide has been reported, but whether normally mineralized bone is formed requires further study.
DOI: 10.1530/EDM-21-0096
Journal: Endocrinology, Diabetes & Metabolism Case Reports
PubMed URL: 34515659
ISSN: 2052-0573
Type: Journal Article
Appears in Collections:Journal articles

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