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

Journal article

Warren, Annabelle M., Ebeling, Peter R., Grill, Vivian, Seeman, Ego and Sztal-Mazer, Shoshana. (2021). Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinology, Diabetes & Metabolism. 2021(1), pp. 1-5. https://doi.org/10.1530/EDM-21-0096

Publication dates
Authors	Warren, Annabelle M., Ebeling, Peter R., Grill, Vivian, Seeman, Ego and Sztal-Mazer, Shoshana
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.
Keywords	hypophosphatasia; fractures; bone fractures
Year	2021
Journal	Endocrinology, Diabetes & Metabolism
Journal citation	2021 (1), pp. 1-5
Publisher	BioScientifica Ltd.
ISSN	2398-9238
Digital Object Identifier (DOI)	https://doi.org/10.1530/EDM-21-0096
PubMed ID	34515659
Scopus EID	2-s2.0-85121031842
PubMed Central ID	PMC8495717
Open access	Published as ‘gold’ (paid) open access
Research or scholarly	Research
Page range	1-5
Publisher's version	OA_Warren_2021_Bilateral_atypical_femoral_fractures_during_denosumab.pdf License CC BY-NC-ND File Access Level Open
Output status	Published
Online	13 Sep 2021
Publication process dates
Accepted	19 Aug 2021
Deposited	29 Mar 2022

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Bala, Y. and Seeman, Ego. (2015). Bones material constituents and their contribution to bone strength in health, disease, and treatment. Calcified Tissue International. 97(3), pp. 308 - 326. https://doi.org/10.1007/s00223-015-9971-y

A. Michael Parfitt: Enlightened scholar and revered mentor: May 10, 1930-May 18, 2015

Manolagas, Stavros C., Compston, Juliet, Rao, Sudhaker and Seeman, Ego. (2015). A. Michael Parfitt: Enlightened scholar and revered mentor: May 10, 1930-May 18, 2015. Journal of Bone and Mineral Research. 30(8), pp. 1349 - 1355. https://doi.org/10.1002/jbmr.2576

Co-administration of antiresorptive and anabolic agents: A missed opportunity

Seeman, Ego and Martin, T. John. (2015). Co-administration of antiresorptive and anabolic agents: A missed opportunity. Journal of Bone and Mineral Research. 30(5), pp. 753 - 764. https://doi.org/10.1002/jbmr.2496

The ABC of writing a grant proposal

Seeman, Ego. (2015). The ABC of writing a grant proposal. Osteoporosis International. 26(6), pp. 1665 - 1666. https://doi.org/10.1007/s00198-015-3085-2

Growth and age-related abnormalities in cortical structure and fracture risk

Seeman, Ego. (2015). Growth and age-related abnormalities in cortical structure and fracture risk. Endocrinology and Metabolism. 30(4), pp. 419 - 428. https://doi.org/10.3803/EnM.2015.30.4.419

High-resolution in vivo imaging of bone and joints: a window to microarchitecture

Geusens, P., Geusens, P., Chapurlat, Roland D., Chapurlat, Roland D., Schett, G., Ghasem-Zadeh, Ali, Ghasem-Zadeh, Ali, Seeman, Ego, De Jong, J. and Van Den Bergh, J.. (2014). High-resolution in vivo imaging of bone and joints: a window to microarchitecture. Nature Reviews Rheumatology. 10(5), pp. 304 - 313. https://doi.org/10.1038/nrrheum.2014.23

A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images

Zebaze, Roger M., Ghasem-Zadeh, Ali, Mbala, A. and Seeman, Ego. (2013). A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images. Bone. 54(1), pp. 8 - 20. https://doi.org/10.1016/j.bone.2013.01.007

Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy

Chiang, Cherie Ying, Zebaze, Roger M.D., Ghasem-Zadeh, Ali, Iuliano-Burns, Sandra, Hardidge, Andrew and Seeman, Ego. (2013). Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone. 52(1), pp. 360 - 365. https://doi.org/10.1016/j.bone.2012.10.006

Predictors of new and severe vertebral fractures: Results from the HoRIZoN Pivotal Fracture Trial

Wustrack, R., Seeman, Ego, Bucci-Rechtweg, C. and Burch, S.. (2012). Predictors of new and severe vertebral fractures: Results from the HoRIZoN Pivotal Fracture Trial. Osteoporosis International. 23(1), pp. 53 - 58. https://doi.org/10.1007/s00198-011-1664-4

The effect of acute exercise on undercarboxylated osteocalcin in obese men

Levinger, Itamar, Zebaze, Roger M., Jeru, G., Hare, David L., Selig, Steve and Seeman, Ego. (2011). The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporosis International. 22(5), pp. 1621 - 1626. https://doi.org/10.1007/s00198-010-1370-7