This thesis focuses on the effect of inflammatory activity and anti-inflammatory treatment on bone mineral density (BMD) loss in recent-onset rheumatoid arthritis (RA), and on localized BMD loss and the effect of tumor necrosis factor alpha (TNFα) inhibi

Chapter 1 gives a general introduction on RA and OA, addressing especially etiology, bone destruction, including joint damage and BMD loss, and treatment options. With regard to RA, in the past decade a revolution took place in the treatment of patients diagnosed with the disease. New developments in anti-rheumatic treatment, including the advent of biologicals, the more early and intensive treatment approach, and validated monitoring tools resulted in better disease outcomes, higher quality of life, and decrease in sick leave; in other words less burden on patient and society. The BeSt study, acronym for Behandel Strategieën, i.e. treatment strategies, pulls its weight on this revolution. The inventors of the BeSt study introduced a novel study design comparing four different treatment strategies in which treatment adjustments were made continuously when low disease activity, defined as disease activity score (DAS) ≤2.4, was not reached in patients with recent-onset RA. On the other hand, treatment could be tapered to monotherapy in a maintenance dose, and thereafter even to zero when longstanding, i.e. six consecutive months, low disease activity, DAS ≤2.4, or clinical remission, DAS <1.6, was reserved. The treatment strategies were: group 1. sequential monotherapy starting with methotrexate (MTX), group 2. step-up combination therapy starting also with MTX, group 3. initial combination therapy with MTX, sulphasalazine and quickly tapered high dose of prednisone, and group 4. initial combination therapy with MTX and TNFα inhibitor infliximab. In the initial combination groups, group 3 and 4, low disease activity was reached earlier, and therefore a greater reduction of joint damage progression was seen compared to the initial monotherapy groups, group 1 and 2. [1] The studies described in chapters 2-6 and 8 have been conducted as part of the still ongoing BeSt study. One of the hallmarks of RA is bone destruction, including joint damage, and localized and generalized BMD loss. It is known that the inflammation-driven, activated osteoclast, mediated particularly through the osteoprotegerin/receptor activator of NK-kappaB ligand (OPG/RANKL) signaling system, is the most crucial cell in the pathogenesis of joint damage. The direct effect of this inflammation-driven mechanism on BMD loss is less clear. When inflammatory activity plays an important role in the etiology of BMD loss, anti-inflammatory treatment might influence this towards less BMD loss. Nevertheless, on the other hand, the in RA frequently used corticosteroids are notorious in having a catabolic effect on bone. Localized BMD loss in the hands is proposed as an outcome measure for bone involvement in RA. The value of localized BMD loss in an early stage of the disease to predict subsequent destructive disease, compared to other well-known predictors, is not clear. It is thought that, just as in RA, inflammatory activity might play an important role in the development and progression of hand OA. Consequently, strong anti-inflammatory agents, such as TNFα inhibitors, might diminish or stop bone destruction in hand OA.