Rheumatology International

, Volume 37, Issue 11, pp 1891–1898 | Cite as

Serum serotonin levels and bone in rheumatoid arthritis patients

  • Miguel BernardesEmail author
  • Tiago Vieira
  • Raquel Lucas
  • Jorge Pereira
  • Lúcia Costa
  • Francisco Simões-Ventura
  • Maria João Martins


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.


DXA Biochemical markers of bone turnover Wnt/β-catenin/LRPs Other diseases and disorders of/related to bone Osteoimmunology 



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.).


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.

Compliance with ethical standards

Conflict of interest

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].

Supplementary material

296_2017_3836_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 32 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of RheumatologySão João Hospital Center, Alameda Prof. Hernâni MonteiroPortoPortugal
  2. 2.Medicine Department, Faculty of MedicineUniversity of PortoPortoPortugal
  3. 3.Department of Nuclear MedicineSão João Hospital CenterPortoPortugal
  4. 4.EPIUnit-Institute of Public HealthUniversity of PortoPortoPortugal
  5. 5.Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of MedicineUniversity of PortoPortoPortugal
  6. 6.Faculty of MedicineUniversity of Porto (FMUP)PortoPortugal
  7. 7.Unit of Biochemistry, Department of Biomedicine, Faculty of MedicineUniversity of PortoPortoPortugal
  8. 8.Instituto de Investigação e Inovação em Saúde (i3s)University of PortoPortoPortugal

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