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Rate of fracture in patients with glucocorticoid replacement therapy: a systematic review and meta-analysis

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Abstract

Purpose

The association between glucocorticoid replacement therapy for adrenal insufficiency (AI) and osteoporosis is unclear. Fracture is a major cause of morbidity in patients with osteoporosis. This study aims to determine if patients on glucocorticoid replacement therapy for AI have an increased rate of fractures compared to the general population.

Methods

We included all studies with adult patients receiving glucocorticoid replacement therapy for either congenital adrenal hyperplasia (CAH), primary adrenal insufficiency (PAI), or secondary adrenal insufficiency (SAI). Studies without fracture data were excluded, as well as meeting abstracts. Studies with fractures but without a control group were eligible to be included in the systematic review but not in the meta-analysis. The primary outcome was the number of fractures, which was further differentiated into osteoporotic fractures. In addition, the glucocorticoid dose equivalents used were noted whenever possible.

Results

Seventeen studies were included in the systematic review. Seven were used in the meta-analysis of any fracture and six were used for osteoporotic fracture. The reported fracture rate ranged between no fracture to 60.8% in the patient group and no fracture to 43.8% in the control group. The odds ratio (OR) for any fracture was 2.71 (95%CI: 1.36–5.43, P = 0.005) and for osteoporotic fracture 2.76 (95%CI: 2.39–3.19 P < 0.00001), favoring the control group.

Conclusions

Patients with AI on glucocorticoid replacement therapy have a higher rate of fractures compared to the control population.

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Funding

This project was supported by grants from the Magnus Bergvall Foundation (grant number 2017–02138, 2018–02566, and 2019–03149 Henrik Falhammar).

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Authors and Affiliations

  1. Department of Endocrinology, Royal Darwin Hospital, Darwin, NT, Australia

    Ling Li & Henrik Falhammar

  2. Department of Endocrinology, Gold Coast University Hospital, Southport, QLD, Australia

    Ling Li

  3. Department of Endocrinology, Metabolism and Diabetes, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

    Ling Li

  4. Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden

    Sophie Bensing & Henrik Falhammar

  5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Sophie Bensing & Henrik Falhammar

  6. Menzies School of Health Research, Darwin, NT, Australia

    Henrik Falhammar

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  1. Ling Li
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Correspondence to Ling Li.

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L.L. declares that she has no conflict of interest. S.B. declares that she has no conflict of interest. H.F. declares that he has no conflict of interest.

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Li, L., Bensing, S. & Falhammar, H. Rate of fracture in patients with glucocorticoid replacement therapy: a systematic review and meta-analysis. Endocrine 74, 29–37 (2021). https://doi.org/10.1007/s12020-021-02723-z

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