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Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations

Osteoporosis International volume 33, pages 2479–2493 (2022)Cite this article

Abstract

Mini abstract

Early diagnosis of hypophosphatasia (HPP) is challenging. Here, we propose to broaden the diagnostic criteria of HPP by reviewing published data on BMD and fractures in HPP patients. Non-osteoporotic fractures and higher than normal lumbar BMD were recurrent in HPP patients and could be included as diagnostic criteria.

HPP is a genetic disorder caused by autosomal recessive or dominant loss-of-function mutations in the ALPL gene that encodes for tissue-nonspecific alkaline phosphatase (TNSALP). Expressive genetic heterogeneity and varying severity of TNSALP deficiency lead to a wide-ranging presentation of skeletal diseases at different ages that coupled with HPP’s rarity and limitation of biochemical and mutational studies present serious hurdles to early diagnosis and management of HPP. To widen the scope of HPP diagnosis, we assessed the possibility of areal bone mineral density (BMD) as an additional clinical feature of this disease. PubMed, Web of Science, and ScienceDirect were searched with the following keywords: (“Hypophosphatasia OR HPP”) AND (“Bone Mineral Density OR BMD”) AND “Human”. Studies and case reports of subjects with age ≥ 18 years and having BMD data were included. We pooled data from 25 publications comprising 356 subjects (90 males, 266 females). Only four studies had a control group. Biochemical hallmarks, pyridoxal 5′-phosphate (PLP) and phosphoethanolamine (PEA), were reported in fifteen and six studies, respectively. Twenty studies reported genetic data, nineteen studies reported non-vertebral fractures, all studies reported lumbar spine (LS) BMD, and nineteen reported non-vertebral BMD. Higher than normal and normal BMD at LS were reported in three and two studies, respectively. There was marked heterogeneity in BMD at the non-vertebral sites. Higher than normal or normal LS BMD in an adult with minimal or insufficient fractures, pseudofractures, non-healing fractures, fragility fractures, and stress fractures may be included in the diagnostic protocol of HPP. However, genetic testing is recommended for a definitive diagnosis.

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Funding

This study was funded by the Council of Scientific and Industrial Research, Government of India, MLP-2035. CSIR-CDRI Communication Number of this manuscript is: 10420.

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  1. Poonam Mehta, Singh Rajender & Naibedya Chattopadhyay

    Present address: Academy of Scientific and Innovative Research, Ghaziabad, 201002, India

Authors and Affiliations

  1. Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Lucknow, India

    Sreyanko Sadhukhan, Poonam Mehta, Singh Rajender & Naibedya Chattopadhyay

  2. Academy of Scientific and Innovative Research, Ghaziabad, 201002, India

    Sreyanko Sadhukhan

  3. Department of Endocrinology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India

    Sushil Kumar Gupta

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  1. Sreyanko Sadhukhan
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Sadhukhan, S., Mehta, P., Rajender, S. et al. Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations. Osteoporos Int 33, 2479–2493 (2022). https://doi.org/10.1007/s00198-022-06480-1

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