Impact of muscular symptoms and/or pain on disease characteristics, disability, and quality of life in adult patients with hypophosphatasia: A cross-sectional analysis from the Global HPP Registry

Kathryn M Dahir; Priya S Kishnani; Gabriel Ángel Martos-Moreno; Agnès Linglart; Anna Petryk; Cheryl Rockman-Greenberg; Samantha E Martel; Keiichi Ozono; Wolfgang Högler; Lothar Seefried

doi:10.3389/fendo.2023.1138599

Impact of muscular symptoms and/or pain on disease characteristics, disability, and quality of life in adult patients with hypophosphatasia: A cross-sectional analysis from the Global HPP Registry

Front Endocrinol (Lausanne). 2023 Mar 27:14:1138599. doi: 10.3389/fendo.2023.1138599. eCollection 2023.

Authors

Affiliations

¹ Division of Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United States.
² Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.
³ Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
⁴ Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.
⁵ Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
⁶ Department of Endocrinology and Childhood Diabetes, Paris Saclay University, AP-HP and INSERM, Paris, France.
⁷ Department of Global Medical Affairs, Alexion, AstraZeneca Rare Disease, Boston, MA, United States.
⁸ Department of Pediatrics & Child Health and Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
⁹ Department of Epidemiology, Alexion, AstraZeneca Rare Disease, Boston, MA, United States.
¹⁰ Department of Pediatrics, Osaka University, Suita, Osaka, Japan.
¹¹ Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.
¹² Orthopedic Department, University of Würzburg, Würzburg, Germany.

Abstract

Introduction: Hypophosphatasia (HPP) manifests in adults as fractures/pseudofractures, pain, muscle weakness, and other functional impairments. Better phenotypic disease characterization is needed to help recognize disability and treat patients with HPP.

Methods: Baseline/pretreatment demographic, clinical characteristic, and patient-reported disability/health-related quality-of-life (HRQoL) data from adults (≥18 y) in the Global HPP Registry (NCT02306720) were stratified by presence of overt skeletal manifestations (skeletal group) versus muscular/pain manifestations without skeletal manifestations (muscular/pain group) and summarized descriptively. Disability was measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI), and HRQoL using the 36-item Short Form Health Survey (SF-36v2).

Results: Of 468 adults, 300 were classified into the skeletal group and 73 into the muscular/pain group. The skeletal group had a higher median age at baseline (50.1 vs 44.4 y; P=0.047) but a lower median age at first HPP manifestation (12.3 vs 22.1 y; P=0.0473), with more signs and symptoms (median, 4 vs 3; P<0.0001) and involved body systems (median, 3 vs 2; P<0.0001) than the muscular/pain group. More patients in the skeletal group required any use of mobility aids (22.6% vs 3.5%, respectively; P=0.001). Six-Minute Walk test distances walked were similar between groups. SF-36v2 and HAQ-DI scores were similar between groups for physical component summary (n=238; mean [SD]: 40.2 [11.0] vs 43.6 [11.2]; P=0.056), mental component summary (n=238; mean [SD]: 43.6 [11.3] vs 43.8 [11.8]; P=0.902), and HAQ-DI (n=239; median [minimum, maximum]: 0.4 [0.0, 2.7] vs 0.3 [0.0, 2.1]; P=0.22).

Conclusion: Adults with HPP experience similar QoL impairment regardless of skeletal involvement.

Registration: https://clinicaltrials.gov/ct2/show/NCT02306720 and https://www.encepp.eu/encepp/viewResource.htm?id=47907, identifier NCT02306720; EUPAS13514.

Keywords: 6MWT; SF-36; alkaline phosphatase; fracture; health-related quality of life; mobility; pseudofracture; rare diseases.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cross-Sectional Studies
Fractures, Bone*
Humans
Hypophosphatasia* / complications
Hypophosphatasia* / epidemiology
Pain
Quality of Life
Registries

Associated data

ClinicalTrials.gov/NCT02306720

Grants and funding

This study was sponsored by Alexion, AstraZeneca Rare Disease (Boston, MA, USA). The Global HPP Registry is sponsored by Alexion, AstraZeneca Rare Disease, and is overseen by a scientific advisory board comprising HPP clinical experts, including employees of Alexion, AstraZeneca Rare Disease.