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Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison’s disease

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Abstract

Purpose

Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison’s disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement.

Methods

Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN).

Results

Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10−6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient’s age (p = 1.038 × 10−5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD.

Conclusion

Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

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Acknowledgements

We express our gratitude to all our patients with Addison’s disease for their participation and comprehension.

Author contributions

All authors contributed to the study conception. K.F., P.G. and M.F. were involved in study design. Material preparation was performed by P.G., M.R. and M.F. Data collection and analysis was done by K.F., A.S. and M.F. The first draft of the manuscript was written by K.F. and all authors commented and provided feedback to the final version. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Internal Medicine, Poznań University of Medical Sciences, Poznań, Poland

    Katarzyna Furman, Paweł Gut, Marek Ruchała & Marta Fichna

  2. Ludwik Perzyna Regional Hospital, Kalisz, Poland

    Katarzyna Furman

  3. Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland

    Anna Sowińska

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  1. Katarzyna Furman
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Correspondence to Marta Fichna.

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This study was performed in accordance with the principles of the Declaration of Helsinki. Its protocol was approved by the local Ethics Committee of Poznan University of Medical Sciences (decision 68/19). Informed consent was obtained from all individual participants included in the study.

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Furman, K., Gut, P., Sowińska, A. et al. Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison’s disease. Endocrine 84, 711–719 (2024). https://doi.org/10.1007/s12020-024-03709-3

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