Clinical Trial: Bone Resorption, Osteoclastogenesis and Adalimumab

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Bone Resorption, Osteoclastogenesis and Adalimumab

Brief Summary: Osteoclastic bone resorption depends on both the capacity to generate osteoclasts (osteoclastogenesis) and on individual osteoclast activity. The investigators objective is to study the effect of anti-TNF therapy on the number of osteoclast precursors in the peripheral blood of patients with Rheumatoid Arthritis, on in vitro osteoclastogenesis and on osteoclast activity before and during the treatment of patients with Rheumatoid Arthritis with Adalimumab.

Detailed Summary:

Osteoclasts (OCs) are cells specialized in bone degradation that participate in bone and joint destruction in Rheumatoid Arthritis (RA). Experimental models have clearly demonstrated that OCs are essential for local bone resorption in arthritis. In RANKL knockout mice(1; 2), in rats receiving OPG(3-6) or in c-fos(-/-) hTNF transgenic mice(7) induction of arthritis leads to inflammation but not to bone erosion. Systemic osteoporosis is an important comorbidity in RA(8; 9). Increased systemic bone resorption due to OC activation occurs even in early (< 2 years) RA and correlates with disease activity(10). Bisphosphonates are effective in preventing systemic bone loss in inflammatory diseases, but for unknown reasons do not seem to influence periarticular bone erosion and joint destruction. Finally, a systemic factor affecting osteoclastogenesis seems to be present in RA, as shown by an increased formation of OCs from bone marrow of patients with severe arthritis when compared to controls(11).

TNF-alpha is a major pathologic mediator in RA. It may induce bone resorption either directly, stimulating osteoclastogenesis(12; 13) or indirectly, by influencing RANKL, OPG and prostaglandin production by osteoblasts(14; 15). These pathways may be important for the pathophysiology of several diseases such as periodontitis, Rheumatoid arthritis and osteoporosis(16; 17). In mice, TNF-alpha increases the number of osteoclast precursors in vivo but its role may, however, be more complex and implicate also osteoclastogenesis-inhibiting mechanisms(18; 19); in fact, in certain conditions, TNF-alpha may decrease osteoclastogenesis(20), so the in vivo effect of blocking TNF may be difficult to predict from these models.

Anti-TNF agents reduce bone destruction in RA but it is not clear how this effect is achieved since, as described in the p
Sponsor: Université de Sherbrooke

Current Primary Outcome:

  • The number of osteoclast precursor (CD14+) cells in the peripheral blood [ Time Frame: 0, 3 and 6 months ]
  • The number of osteoclasts genereated in vitro [ Time Frame: 0, 3 and 6 months ]
  • The amount of bone resorption in vitro [ Time Frame: 0, 3 and 6 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Osteoclast differentiation in the presence of exogenous Adalimumab [ Time Frame: 0, 3 and 6 months ]
  • Disease activity defined by the DAS28 score [ Time Frame: 0, 3 and 6 months ]
  • Change in functionnal status measured by the M-HAQ [ Time Frame: 0, 3 and 6 months ]


Original Secondary Outcome: Same as current

Information By: Université de Sherbrooke

Dates:
Date Received: December 10, 2013
Date Started: May 2013
Date Completion:
Last Updated: October 26, 2016
Last Verified: December 2013