J Rheum Dis.  2016 Dec;23(6):356-362. 10.4078/jrd.2016.23.6.356.

Tumor Necrosis Factor Blockade Stimulates Circulating Osteoblastic Lineage Cells Activity while Reducing Circulating Osteoclasts

Affiliations
  • 1Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea. parkwon@inha.ac.kr

Abstract


OBJECTIVE
This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients.
METHODS
Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts.
RESULTS
The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade.
CONCLUSION
The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.

Keyword

Rheumatoid arthritis; Osteoblast; Osteoclast; Biologic therapy; Bone

MeSH Terms

Acute-Phase Proteins
Adalimumab
Alkaline Phosphatase
Arthritis, Rheumatoid
Biological Therapy
Bone Remodeling
Bone Resorption
Etanercept
Female
Humans
Infliximab
Metabolism
Methotrexate
Osteoblasts*
Osteocalcin
Osteoclasts*
Osteogenesis
Tumor Necrosis Factor-alpha*
Acute-Phase Proteins
Adalimumab
Alkaline Phosphatase
Etanercept
Infliximab
Methotrexate
Osteocalcin
Tumor Necrosis Factor-alpha
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