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Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio

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Abstract

Summary

The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration.

Introduction

Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters.

Methods

PBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3 weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated.

Results

PBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration.

Conclusion

Monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.

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Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2011/23781-2 and Conselho Nacional de Ciência e Tecnologia (CNPQ) #301805/2013-0 (RMRP).

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Authors and Affiliations

  1. Bone Metabolism Laboratory, Rheumatology Division, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR, Av. Dr. Arnaldo, 455, 3° andar, sala 3193, São Paulo, SP, 01246-903, Brazil

    V.F. Caparbo, C.G.S. Saad, J.C. Moraes & R.M.R. Pereira

  2. Département de médecine, Service de Rhumatologie, Faculté de médecine et des sciences de la santé Université de Sherbrooke, Sherbrooke, Canada

    A.J. de Brum-Fernandes

Authors
  1. V.F. Caparbo
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  2. C.G.S. Saad
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  3. J.C. Moraes
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  4. A.J. de Brum-Fernandes
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  5. R.M.R. Pereira
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Corresponding author

Correspondence to R.M.R. Pereira.

Ethics declarations

This study was approved by the Local Ethics Committee on Human Research at the Sao Paulo University-CAPPesq 0061/11.

Conflicts of interest

Valeria F. Caparbo, Carla GS Saad, Julio CB Moares, Artur J de Brum-Fernandes, and Rosa MR Pereira declare no conflicts of interest and no competing financial interests.

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Caparbo, V., Saad, C., Moraes, J. et al. Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio. Osteoporos Int 29, 2565–2573 (2018). https://doi.org/10.1007/s00198-018-4629-z

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