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A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients

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Abstract

Summary

Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy.

Introduction

Hypophosphatasia (HPP) is an inherited disorder associated with impaired primary mineralisation of osteoid (osteomalacia). HPP may be misdiagnosed as osteoporosis, a reduction in the volume of normally mineralized bone. Both illnesses may result in fragility fractures, although stress and atypical fractures are more common in HPP. Antiresorptive therapy, first-line treatment for osteoporosis, is relatively contraindicated in HPP. Misdiagnosis and mistreatment can be avoided by recognising a low serum alkaline phosphatase (ALP). Our aim was to determine the prevalence of a low ALP (< 30 IU/L) in patients attending an osteoporosis clinic, in a hospital-wide setting, and in a group of patients with atypical femoral fractures (AFF).

Methods

This was a retrospective study of patients attending an osteoporosis clinic at a tertiary hospital during 8 years (2012–2020). Patients were categorised into those with a transiently low ALP, those with low ALP on ≥ 2 occasions but not the majority of measurements, and those with a persistently low ALP. ALP levels were also assessed in hospital-wide records and a group of patients with AFF.

Results

Of 1839 patients attending an osteoporosis clinic, 168 (9%) had ≥ 1 low ALP, 50 (2.7%) had low ALP for ≥ 2 months, and seven (0.4%) had persistently low ALP levels. HPP was diagnosed in five patients, four of whom had persistently low ALP levels. The prevalence of HPP was 0.3% in the osteoporosis clinic and 3% in patients with ≥ 1 low ALP. Low ALP occurred in 0.6% of all hospital patients and 2/22 with AFF.

Conclusion

Persistently low ALP in osteoporosis clinic attendees is easy to identify and signals the possibility of hypophosphatasia, a condition that may be mistaken for osteoporosis and incorrectly treated with antiresorptive therapy.

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Authors and Affiliations

  1. Department of Endocrinology & Diabetes, Alfred Health, Melbourne, Australia

    Elisabeth Ng, Claudia Ashkar, Hans G. Schneider & Shoshana Sztal-Mazer

  2. Department of Endocrinology, Monash Health, Clayton, Australia

    Elisabeth Ng, Hanh Nguyen & Peter R. Ebeling

  3. Department of Medicine, University of Melbourne, Melbourne, Australia

    Ego Seeman

  4. Department of Endocrinology, Austin Health, Melbourne, Australia

    Ego Seeman

  5. Clinical Biochemistry Unit, Alfred Pathology Service, Alfred Health, Melbourne, Australia

    Hans G. Schneider

  6. School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

    Hans G. Schneider & Shoshana Sztal-Mazer

  7. Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia

    Hanh Nguyen & Peter R. Ebeling

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  1. Elisabeth Ng
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Correspondence to Elisabeth Ng.

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Ng, E., Ashkar, C., Seeman, E. et al. A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients. Osteoporos Int 34, 327–337 (2023). https://doi.org/10.1007/s00198-022-06597-3

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