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Bone histomorphometry in acromegaly patients with fragility vertebral fractures

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Abstract

Context

The high risk of vertebral fractures (VFs) in acromegaly patients despite normal bone mineral density (BMD) is well known. The reasons for this paradoxical finding of skeleton fragility are poorly understood due to the limited data on bone histomorphometry in acromegaly.

Objective

This study aimed to analyze histomorphometric parameters including bone microarchitecture in acromegaly patients with VFs and normal BMD compared to normal subjects, and also to evaluate the differences between active and controlled acromegaly patients.

Patients and methods

Forty-seven acromegaly patients (17 active, 30 controlled), median (range) age 57 years (30–88) were evaluated for bone turnover, morphometric VFs and BMD by dual-energy X-ray absorptiometry at lumbar spine and hip; 12 patients with VFs and normal BMD underwent iliac crest bone biopsy; 12 biopsies were taken at the autopsy in healthy sex and age—matched control subjects.

Results

The histomorphometric evaluation of acromegaly fractured patients was compared with that of normal controls and showed significantly reduced median (range) levels of bone volume/tissue volume (BV/TV: 15.37% (7.93–26.75) vs. 18.61% (11.75–27.31), p = 0.036), trabecular thickness (TbTh: 77.6 µm (61.7–88.3) vs. 82.7 µm (72.3–92.0) p = 0.045), with increased trabecular separation (TbSp: 536.4 µm (356.2–900.6) vs. 370.3 µm (377.1–546.3) p = 0.038) and increased cortical thickness (1268 μm (752–2521) vs. 1065 μm (851–1205) p = 0.025) and porosity (11.9% (10.2–13.3) vs. 4.8% (1.6–8.8) p = 0.0008). While active acromegaly patients showed histomophometric features of increased bone turnover, patients with controlled disease presented normal bone turnover with significantly lower osteoblastic activity, expressed as osteoblast number (p = 0.001), active osteoblasts and vigor (p = 0.014) in the presence of reduced osteocyte number (p = 0.008) compared to active disease.

Conclusions

The apparent paradox of bone fragility in acromegaly patients with a normal BMD can be explained by increased cortical thickness and porosity and reduced trabecular thickness with increased trabecular separation. These structural and microarchitectural abnormalities persist in the controlled phase of acromegaly despite bone turnover normalization. The main determinant of bone disease after hormonal control is severe osteoblastic dysfunction.

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Authors and Affiliations

  1. Department of Medicine, Medicina Interna D, University of Verona, Piazzale Scuro, Policlinico G.B. Rossi, 37134, Verona, Italy

    L. Dalle Carbonare, V. Micheletti, E. Cosaro & M. V. Davì

  2. Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy

    M. T. Valenti & M. Mottes

  3. Endocrinology Unit, Ospedale Pederzoli, Peschiera del Garda, Verona, Italy

    G. Francia

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  1. L. Dalle Carbonare
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  2. V. Micheletti
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  4. M. T. Valenti
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  5. M. Mottes
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Correspondence to L. Dalle Carbonare.

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All procedures were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Carbonare, L.D., Micheletti, V., Cosaro, E. et al. Bone histomorphometry in acromegaly patients with fragility vertebral fractures. Pituitary 21, 56–64 (2018). https://doi.org/10.1007/s11102-017-0847-1

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  • DOI: https://doi.org/10.1007/s11102-017-0847-1

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