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Serum serotonin levels and bone in rheumatoid arthritis patients

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Abstract

In rheumatoid arthritis (RA), a disease characterized by bone loss, increased levels of serotonin have been reported. Recent studies have demonstrated a role for circulating serotonin as a regulator of osteoblastogenesis, inhibiting bone formation. Thus, we measured serum serotonin levels (SSL) in a Portuguese sample of 205 RA patients and related these to anthropometric variables, disease parameters, serum bone biomarkers, and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry at several sites (total proximal femur, lumbar spine, left hand, and left second proximal phalange). SSL were inversely associated with body mass index (BMI) in RA women (r = − 0.218; p = 0.005), independent of exposure to biologics and/or bisphosphonates. Among biologic naïves, there was an inverse association between SSL and osteoprotegerin in RA women (r = − 0.260; p = 0.022). Serum β-CTX and dickkopf-1 were strongly associated with SSL in RA men not treated with bisphosphonates (r = 0.590; p < 0.001/r = 0.387; p = 0.031, respectively). There was also an inverse association between SSL and sclerostin in RA men (r = − 0.374; p < 0.05), stronger among biologic naïve or bisphosphonates-unexposed RA men. In crude models, SSL presented as a significant negative predictor of total proximal femur BMD in RA women as well as in postmenopausal RA women. After adjustment for BMI, disease duration, and years of menopause, SSL remained a significant negative predictor of total proximal femur BMD only in postmenopausal RA women. Our data reinforce a role, despite weak, for circulating serotonin in regulating bone mass in RA patients, with some differences in terms of gender and anatomical sites.

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Acknowledgements

Authors’ roles: MB conceived the idea of the study, designed the study, coordinated the project, participated in patient recruitment and in data acquisition, drafted the manuscript, and takes responsibility for the integrity of the data analysis. RL performed the statistical analysis, revised the manuscript, and takes responsibility for the integrity of the data analysis. TV and JP performed DXA evaluations and approved the final version of the manuscript. LC participated in patient recruitment and approved the final version of the manuscript. FSV coordinated the project, participated in patient recruitment and revised the manuscript. MJM conceived the idea of the study, coordinated the experimental work (ELISA), assisted in manuscript drafting, and takes responsibility for the integrity of the data analysis. The authors wish to acknowledge Associação Nacional de Reumatologia for the doctoral grant, Conceição Gonçalves (MSc) from the Laboratório Nobre in the Faculty of Medicine of the University of Porto, the nursing Service of Rheumatology Day Hospital of São João Hospital Center, and the clinicians from the Rheumatology Department of São João Hospital Center, especially Alexandra Bernardo (M.D.) and Sofia Pimenta (M.D.).

Funding

Associação Nacional de Reumatologia, the study sponsor, had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Rheumatology, São João Hospital Center, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Miguel Bernardes & Lúcia Costa

  2. Medicine Department, Faculty of Medicine, University of Porto, Porto, Portugal

    Miguel Bernardes

  3. Department of Nuclear Medicine, São João Hospital Center, Porto, Portugal

    Tiago Vieira & Jorge Pereira

  4. EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal

    Raquel Lucas

  5. Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal

    Raquel Lucas

  6. Faculty of Medicine, University of Porto (FMUP), Porto, Portugal

    Francisco Simões-Ventura

  7. Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal

    Maria João Martins

  8. Instituto de Investigação e Inovação em Saúde (i3s), University of Porto, Porto, Portugal

    Maria João Martins

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  1. Miguel Bernardes
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Correspondence to Miguel Bernardes.

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The authors declare there is no conflict of interests regarding the publication of this paper.

Ethical approval

The study protocol was approved by the local Ethical Committee, Comissão de Ética para a Saúde do Centro Hospitalar de São João do Porto, in accordance with the principles of the 1964 Declaration of Helsinki [38].

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Bernardes, M., Vieira, T., Lucas, R. et al. Serum serotonin levels and bone in rheumatoid arthritis patients. Rheumatol Int 37, 1891–1898 (2017). https://doi.org/10.1007/s00296-017-3836-9

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