Caution should be taken in interpreting these data because measurements were performed by dual-energy quantitative computed

tomography, which has a relatively low precision. GLUT inhibitor Although the results from other individual studies thereafter with low- to medium-dose GC therapy in RA are inconsistent [3, 6, 15–17], a meta-analysis showed strong correlations between the cumulative GC dose and a decline in bone mineral density (BMD) and between the daily dose and risk of fracture [18]. In RA, bone loss in GC-naive patients may develop; this mainly occurs during the first months of disease [19, 20] and especially in patients with active disease [21–23]. Systemic inflammation, SHP099 molecular weight not only via interleukin-1 (IL-1) and tumor necrosis factor (TNF) leads to bone loss, but also via decreased weight-bearing physical activity [24], GDC-0449 molecular weight because of pain and stiffness [25]. The impaired mobility also reduces exposure to sunlight which is needed for sufficient amounts of vitamin D, increasing the risk of developing osteoporosis [26, 27] and the risk of falls, leading to fractures. Furthermore, RA patients are mostly women of whom the majority are postmenopausal [25], thus comprising

individuals already at high risk of developing osteoporosis. In these circumstances, the negative effects of GCs might be the trigger for definite worsening of the BMD. Although it has been established that preventive medication for osteoporosis (i.e., calcium, vitamin D, bisphosphonates) is effective in inhibiting bone loss and their use is recommended [28], it is also known that adherence to bisphosphonate therapy is low, and this is associated with an increased fracture risk [29]. This makes the

fear for development of osteoporosis with chronic prednisone therapy of 10 mg daily in RA patients a realistic concern despite the prescription of preventive therapy. On the other hand, one could argue that effective therapy could decrease the risk of osteoporosis induced by disease activity. Both treatment strategies in the CAMERA-II trial are treat-to-target strategies aiming at remission, PD184352 (CI-1040) and it might be that the inclusion of prednisone is not as harmful as expected based on earlier reports. The net effects of GCs on bone in RA thus remain controversial: do favorable effects on the inflammatory disease and thus on physical activity outweigh the negative effects on bone (see Fig. 1)? Fig. 1 BMD is influenced by GCs and active RA. Both GC therapy and active rheumatoid arthritis (RA) are thought to influence bone mineral density (BMD) in a negative way. However, GCs decrease the disease activity of RA. Therefore, they may exert a positive effect on BMD by lowering inflammation. Actually, the net effect is unknown.