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Determinants of skeletal fragility in acromegaly: a systematic review and meta-analysis

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Abstract

Purpose

Vertebral fractures (VFs) are a potential complication in acromegaly. However, the etiology of this skeletal fragility is unknown. This review aimed to evaluate the effect of acromegaly on VFs, bone turnover, areal bone mineral density (aBMD), and bone quality/microarchitecture. The effect of disease activity and gonadal status in these determinants of skeletal fragility was also evaluated.

Methods

Articles published in English until September 6, 2020 on PubMed and Embase that reported at least one determinant of skeletal fragility in acromegalic patients, were included. Odds ratio (OR) to evaluate the risk of VFs and the standardized mean difference (SMD) to evaluate bone turnover, aBMD and bone quality/microarchitecture were calculated.

Results

Fifty-eight studies met eligibility criteria, assembling a total of 2412 acromegalic patients. Of these, 49 studies were included in the meta-analysis. Acromegalic patients, when compared to non-acromegalic patients, had higher risk of VFs [OR 7.00; 95% confidence interval (CI) 2.80–17.52; p < 0.0001], higher bone formation (SMD 1.14; 95% CI 0.69–1.59; p < 0.00001), higher bone resorption (SMD 0.60; 95% CI 0.09–1.10; p = 0.02) and higher aBMD at the femoral neck (SMD 0.36; 95% CI 0.15–0.57; p = 0.0009). No significant differences were found regarding aBMD at lumbar spine. Considering the results of the different techniques evaluating bone quality/microarchitecture, the main reported alterations were a decrease in trabecular bone thickness and density, and an increase in trabecular separation. The presence of active disease and/or hypogonadism were associated with worst results.

Conclusion

Patients with acromegaly are at increased risk of VFs, mainly because of deterioration in bone microarchitecture.

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Data availability

The datasets generated during the current study are not publicly available but are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

No funding was received for conducting this study.

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Author notes

  1. Cláudia Ribeiro de Moura and Sara Campos Lopes shared co-first authorship.

Authors and Affiliations

  1. School of Medicine, University of Minho, Braga, Portugal

    Cláudia Ribeiro de Moura

  2. Endocrinology Department, Hospital de Braga, Braga, Portugal

    Sara Campos Lopes & Ana Margarida Monteiro

Authors
  1. Cláudia Ribeiro de Moura
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  2. Sara Campos Lopes
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  3. Ana Margarida Monteiro
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Contributions

The study was conceptualized by AMM and supervised by AMM and SCL. All authors contributed to the study design. Material preparation, data collection, selection, and analysis were performed by CRM and SCL. Discrepancies in data selection were solved by AMM (senior). The first draft of the manuscript text was written by CRM and SCL and all authors participated in the revision of the manuscript. All authors read and approved the final manuscript. CRM and SCL should be considered as equally contributing authors (shared co-first authorship).

Corresponding author

Correspondence to Sara Campos Lopes.

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Conflict of interest

The authors have nothing to disclose.

Ethical approval

The study followed the recommended guidelines for good clinical practice and ethics. The research protocol was submitted and approved by the Ethics Committee for Health of Hospital de Braga and the Ethics Committee for Life and Health Sciences of University of Minho. The protocol was registered with the International Prospective Register of Systematic Reviews (Registration No. CRD42021230349) in February 2021.

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Ribeiro de Moura, C., Campos Lopes, S. & Monteiro, A.M. Determinants of skeletal fragility in acromegaly: a systematic review and meta-analysis. Pituitary 25, 780–794 (2022). https://doi.org/10.1007/s11102-022-01256-6

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  • DOI: https://doi.org/10.1007/s11102-022-01256-6

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