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Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study

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Abstract

Summary

Hypophosphatasia (HPP) is a rare disease affecting bone mineralization. Adults with HPP have an increased occurrence of low-energy fractures, which cannot be explained by reduced bone mass assessed by dual energy X-ray absorptiometry. The bone phenotype in adults with HPP requires further studies investigating bone strength and bone structural parameters.

Introduction

Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism, characterized by broad-ranging clinical manifestations and severity. However, studies investigating the clinical spectrum in adults with HPP compared to a control group are scarce. The aim of this study was to evaluate biochemical and clinical characteristics as well as bone health in a Danish cohort of adults with HPP.

Methods

We conducted a cross-sectional study assessing biochemical parameters, fracture prevalence, bone mineral density (BMD), bone turnover markers, physical performance and pain characteristics in 40 adults with HPP and 40 sex-, age-, BMI- and menopausal status-matched healthy controls.

Results

Patients with HPP had a significantly higher prevalence of non-vertebral, low-energy fractures (p =  < 0.001). BMD at the lumbar spine, total hip, femoral neck, forearm and whole body did not differ between the groups. Low levels of the bone-specific alkaline phosphatase correlated significantly with higher BMD at the lumbar spine and femoral neck in both groups. The bone formation marker N-terminal propeptide of type 1 procollagen was significantly lower in patients with HPP than healthy controls (p = 0.006). Adults with HPP had significantly reduced walking capability (p =  < 0.001) and lower body strength (p =  < 0.001). Chronic pain was significantly more prevalent in adults with HPP than the control group (p = 0.029).

Conclusions

The increased occurrence of low-energy fractures in adults with HPP is not explained by low BMD. Adults with HPP have reduced physical performance when compared with healthy controls.

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Funding

This research was supported by the A.P. Møller Foundation for the Advancement of Medical Science (Journalnr. 17-L-0254) and the Danish Osteoporosis Association.

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Authors and Affiliations

  1. Department of Endocrinology, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650, Hvidovre, Denmark

    Nicola Hepp & Jens-Erik Beck Jensen

  2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3 B, 2200, Copenhagen, Denmark

    Nicola Hepp, Niklas Rye Jørgensen & Jens-Erik Beck Jensen

  3. Department of Clinical Genetics, Aalborg University Hospital, Ladegaardsgade 5, 9000, Aalborg C, Denmark

    Anja Lisbeth Frederiksen

  4. Department of Clinical Research, Aalborg University, Fredrik Bajers Vej 7K, 9220, Aalborg Ø, Denmark

    Anja Lisbeth Frederiksen

  5. Department of Clinical Genetics, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Morten Duno

  6. Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13, 2600, Glostrup, Denmark

    Niklas Rye Jørgensen

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  1. Nicola Hepp
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Corresponding author

Correspondence to Nicola Hepp.

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Competing interests

AFL, MD and NRJ have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. NH has received research funding from Alexion, AstraZeneca Rare Disease and lecturer fees from Gedeon Richter and UCB. JEBJ is a board member in Eli Lilly, Amgen, Gedeon Richter and UCB, received funding from Eli Lilly and Amgen and consulting fees from UCB, Giliad and Amgen.

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Hepp, N., Frederiksen, A.L., Duno, M. et al. Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study. Osteoporos Int 33, 2595–2605 (2022). https://doi.org/10.1007/s00198-022-06536-2

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  • DOI: https://doi.org/10.1007/s00198-022-06536-2

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