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Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly

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Abstract

Purpose

Acromegaly is a cause of secondary osteoporosis and is associated with increased risk of vertebral fractures (VFs). The influence of exon 3-deleted isoform of growth hormone receptor (d3-GHR) on bone microarchitecture has not been studied in acromegaly.

Aim

The aim of this study was to analyze the associations between d3-GHR isoform and bone mineral density (BMD), bone microarchitecture, and VFs in acromegaly patients.

Methods

Consecutive acromegaly patients treated at a single reference center were included. BMD was analyzed using dual-energy X-ray absorptiometry (DXA) and bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The presence of moderate to severe VFs was assessed by thoracic and lumbar X-ray. GHR genotyping was analyzed by PCR, and full-length isoform of GHR (fl-GHR) was represented by a 935-bp fragment and d3-GHR by a 532-bp fragment.

Results

Eighty-nine patients were included [56 females; median age at diagnosis: 43 years (17–78)]. Disease was uncontrolled in 63% of patients. At least one d3-GHR allele was present in 60% of patients. Frequency of active disease (p = 0.276) and hypogonadism (p = 1.000) was not different between patients with fl-GHR and those with at least one d3-GHR. There was no difference in any DXA or HR-pQCT parameters between patients with fl-GHR and those with d3-GHR. Significant VFs were observed in 14% of patients, but there was no difference in frequency between patients with fl-GHR and those with at least one d3-GHR allele (p = 0.578).

Conclusions

Presence of d3-GHR was not associated with worse BMD or bone microarchitecture or with higher frequency of significant VFs.

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Authors and Affiliations

  1. Neuroendocrinology Research Center, Rio de Janeiro, Brazil

    J. Pontes, L. Kasuki & M. R. Gadelha

  2. Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    M. Madeira, F. de Paula Paranhos Neto, L. M. C. de Mendonça, M. L. F. Farias & M. R. Gadelha

  3. Neuropathology and Molecular Genetic Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil

    C. H. A. Lima, L. L. Ogino & M. R. Gadelha

  4. Neuroendocrine Unit, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil

    L. Kasuki & M. R. Gadelha

  5. Rua Professor Rodolpho Paulo Rocco, 255, 9° andar, Setor 9F, Sala de Pesquisa em Neuroendocrinologia IIha do Fundão, Rio De Janeiro, 21941-913, Brazil

    M. R. Gadelha

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  1. J. Pontes
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Pontes, J., Madeira, M., Lima, C.H.A. et al. Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly. J Endocrinol Invest 43, 163–171 (2020). https://doi.org/10.1007/s40618-019-01096-5

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