Window of Opportunity: Circulating Osteoblast Precursors Were Decreased afterInfliximab Therapy in Patients with Ankylosing Spondylitis.

초록

Background: It was known TNF alpha blocker therapy had little or no effect on new bone formation or structural remodeling in patients with ankylosing spondylitis (AS). Objective: We studied the differentiation and activity of osteoblast by novel cell culture technique of osteoblast in peripheral blood and other methods in candidates for infliximab therapy with AS and controls. 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, cells were transferred to differentiation medium and cultured for 3 weeks. They 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 1) the numbers of circulating osteoblast precursors in peripheral blood, 2) the OD of alizarin S red staining of circulating osteoblast precursors, 3) total procollagen type 1 N-terminal propeptide (P1NP) as osteoprogenitor marker, osteocalcin as mature osteoblast marker in patients with AS and in healthy controls at baseline and 14 weeks after infliximab therapy in AS patients. Results: The serum level of P1NP (osteoprogenitor marker) was significantly higher in patients with AS than in the controls (p = 008), but that of osteocalcin (mature osteoblast marker) was not. 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), but that of osteocalcin was increased (p = 0.007). Conclusions: These results support the hypothesis, ’window of opportunity’ that acute inflammation resolved completely but mature lesion could not alter