Background Many authors tried to elucidate the relationship among the inflammation, osteoblast activity or new bone formation, and adipogenesis in patients with ankylosing spondylitis (AS). But the results were disappointing.
Objectives We investigated the relationship among the inflammation, osteoblast activity or new bone formation, and adipogenesis in patients with AS by novel cell culture technique of osteoblast in peripheral blood and other methods.
Methods Male sixteen individuals with AS were enrolled. They met modified New York criteria and were candidates for infliximab therapy. Sex and age matched nineteen controls were also recruited. Peripheral blood mononuclear cells were collected and cultured in growth medium. Once cell multi-layering has been observed (about 7 days), cells were transferred to differentiation medium and cultured for 3 weeks. Cells were then fixed and stained with alizarin S stain to detect any calcified nodules. The optical density (OD) of alizarin S was measured for quantitative analysis.
We evaluated the numbers, the differences and relationship of 1) the numbers of circulating osteoblast precursors in peripheral blood, 2) the OD of alizarin S red staining of circulating osteoblast precursors, 3) P1NP (total procollagen type 1 N-terminal propeptide), c-terminal telopeptide (CTX), osteocalcin, triglyceride, low density lipoprotein cholesterol (LDL), apolipoprotein A-1, apolipoprotein B, lipoportein (a) with enzyme linked immunosorbent assay (ELISA), 4) erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) before and after 14 week infliximab therapy, 5) bone densitometry (BMD) before infliximab therapy in patients with AS.
Results The number of osteoblast precursor cells and optic density of alizarin S were decreased after infliximab therapy (p=0.028 for optic density of alizarin S). The serum level of P1NP was decreased after infliximab therapy (p=0.002). The serum level of triglyceride was tend to increased, but that of lipoprotein (a) was decreased (p=0.07, p=0.007 separately).
There were positive correlation between the BASDAI and the serum level of triglyceride (r =0.666, p=0.005), ESR and lipoprotein (a) (r =0.594, p=0.015), CRP and CTX (r =0.648, p=0.012), CRP and P1NP (r =0.631, p=0.016); negative correlation between BASDAI and femur total T score of BMD (r = -0.79, p=0.006) before infliximab therapy. They showed positive correlation between the difference of the serum level of LDL and that of osteocalcin (r =0.566, p=0.022), Alizarin S OD and apoprotein B (r =0.943, p=0.005), Alizarin S OD and osteocalcin (r =0.829, p=0.042); negative correlation between the difference of the serum level of LDL and ESR (r = -0.614, p=0.011) before and after infliximab therapy.
Conclusions The circulating osteoblasts in peripheral blood and the serum level of P1NP were decreased significantly after 14 weeks of infliximab therapy. This result could be indirect evidence that infliximab therapy appeared to diminish osteoblast activity or new bone formation in patients with AS. There were strong relationship among inflammation, osteoblast activity, and adipogenesis before and after infliximab therapy in patients with AS.
Disclosure of Interest S.-R. Kwon Grant/research support from: From Celltrion, Korea, Republic of, W. park: None declared, M.-J. Son: None declared, M.-J. Lim: None declared, K.-H. Jung: None declared