Atypical Femoral Fracture in Hypophosphatasia: A Systematic Review

Nipith Charoenngam; Jerapas Thongpiya; Pitchaporn Yingchoncharoen; Ben Ponvilawan; Mehmet S Marangoz; Jirat Chenbhanich; Patompong Ungprasert

doi:10.1155/2023/5544148

Atypical Femoral Fracture in Hypophosphatasia: A Systematic Review

Int J Endocrinol. 2023 Sep 12:2023:5544148. doi: 10.1155/2023/5544148. eCollection 2023.

Authors

Nipith Charoenngam^{1

2}, Jerapas Thongpiya³, Pitchaporn Yingchoncharoen³, Ben Ponvilawan⁴, Mehmet S Marangoz⁵, Jirat Chenbhanich⁶, Patompong Ungprasert⁷

Affiliations

¹ Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.
² Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
⁴ Department of Medicine, University of Kansas Missouri Medical Center, Jefferson, MO, USA.
⁵ Department of Endocrinology and Metabolism, Mount Auburn Hospital, Cambridge, MA, USA.
⁶ Department of Genetics and Genomic Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
⁷ Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio, USA.

Abstract

Objective: To summarize the characteristics of all reported patients with hypophosphatasia (HPP) who sustained atypical femoral fracture (AFF) and identify all available evidence to quantify the rate of coexistence between HPP and AFF.

Methods: Potentially eligible articles were identified from the MEDLINE and EMBASE databases from its inception to September 2022, using a search strategy consisting of terms related to "Hypophosphatasia" and "Atypical femoral fracture." Eligible articles must report one of the following information: (1) individual data of patients diagnosed with HPP and AFF, (2) prevalence of HPP among patients with AFF, or (3) prevalence of AFF among patients of HPP. Characteristics of patients reported in each study were extracted.

Results: A total of 148 articles were identified. After the systematic review, 24 articles met the eligibility criteria. A total of 28 patients with AFF and HPP were identified. The mean ± SD age of the reported patients was 53.8 ± 12.5 years, and 22 patients (78.6%) were female. Nine patients (32.1%) received antiresorptive medication (bisphosphonate and/or denosumab), and two patients (7.1%) received teriparatide prior to the development of AFF. Seven (25.0%) and eighteen (64.3%) patients sustained unilateral and bilateral AFF, respectively (laterality not reported in three cases). Thirteen patients (46.4%) had a history of fractures at other sites. Four (14.3%) and seven (25.0%) patients received asfotase alfa and teriparatide after sustaining AFF. Two studies reported the prevalence of AFF among patients with HPP of approximately 10%. One study reported one HPP patient in a cohort of 72 patients with AFF.

Conclusions: Based on the limited evidence, AFF occurred in up to 10% of patients with HPP. Based on the 28 case reports, about two-thirds did not receive antiresorptive treatment, suggesting that the HPP itself could potentially be a risk factor for AFF.