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

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.

Figure 1

SF-36v2 domain scores at baseline. Mean scores are shown. The SF-36v2 scale is 0 to 100; 50 is average for the general population. SF-36v2, 36-item Short Form Survey version 2. Mean scores are shown; scale 0–100 (50 is average, and lower scores represent more disability. Mean (SD) scores for each domain were as follows for skeletal vs muscular/pain groups, respectively: vitality, 42.8 (10.7) vs 42.2 (11.5), P=0.720; physical functioning, 41.3 (10.9) vs 45.4 (10.7), P=0.022; bodily pain, 39.3 (10.3) vs 42.0 (11.7), P=0.112; general health perceptions, 41.4 (10.8) vs 44.0 (12.0), P=0.141; physical role functioning, 40.1 (11.6) vs 42.4 (11.8), P=0.233; emotional role functioning, 41.8 (12.3) vs 43.4 (12.6), P=0.409; social role functioning, 41.4 (12.1) vs 43.6 (13.3), P=0.282; and mental health, 43.3 (10.5) vs 44.6 (10.8), P=0.470.

Figure 2

HAQ-DI scores among patients with and without skeletal manifestations. HAQ-DI score range is 0 (without any difficulty) to 3 (unable to do). HAQ-DI, Health Assessment Questionnaire–Disability Index. Lines indicate median scores; boxes, quartiles (Q) 1 and 3; dots, minimum and maximum.

Figure 3

Use of assistive devices or mobility aids at baseline. Percentages of patients in the skeletal and muscular/pain groups with any or some use of mobility aids are shown.

Figure 4

6-Minute Walk Test distance walked at baseline. In healthy adults, the 6-Minute Walk Test distance typically ranges from 400 to 700 m. Lines indicate median scores; boxes, quartiles (Q) 1 and 3; dots, minimum and maximum distance walked.