Paradoxical elevation of serum TRACP5b levels despite increase in lumbar spine bone mineral density during anti-TNFα therapy in patients with inflammatory rheumatic disease: a 2-year prospective assessment of bone mass, bone metabolism, and the trabecular bone score.

Abstract

To examine the impact of long-term anti-TNFα therapy on bone mass, bone metabolism, and the trabecular bone score (TBS) in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). In eight patients with RA and 12 with AS, bone mineral densities (BMDs) of the lumbar spine (LS), left and right femoral neck, and total skeleton were measured using dual X-ray absorptiometry at baseline and then at 6, 12, and 24 months after anti TNFα therapy. The TBS was also calculated. At baseline and at 1, 3, 6, 12, 18, and 24 months, bone metabolism was assessed by measurements of pro-collagen-I carboxyterminal propeptide (PICP), osteocalcin, and bone alkaline phosphatase levels in the serum, which are indicative of bone formation and β-isomerized carboxy-terminal telopeptide of type-I collagen (β-CTX-I) and serum isoform 5b of tartrate-resistant acid phosphatase (TRACP5b) levels in the serum, which are indicative of bone resorption. In patients with RA, the LS T-score increased (3.2%, p<0.001) and the TBS progressively decreased (-3.9%, p=0.03). In patients with AS, the LS BMD and T-score increased (4.3% and 6.2%, respectively; p<0.001) with no significant change in the TBS. Serum TRACP5b levels dramatically increased in both groups (227% in patients with RA and 150% in those with AS, p<0.001), while β-CTX-I levels did not change. Serum osteocalcin and PICP levels showed a transitory increase in patients with AS. Long-term anti-TNFα therapy increased LS bone mass and affected bone quality (TBS) with little impact on bone remodeling. Conversely, TRACP5b levels dramatically increased during anti-TNFα therapy but without any detrimental effect on bone mass.