Abstract
IntroductionLocal bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN) and osteoblast stimulation with parathyroid hormone (PTH).MethodsArthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis.ResultsLocally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction.ConclusionsNo local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.
Highlights
Local bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation
Studies indicate that the bone formation is less pronounced in RA compared to the bone resorption [2,3], and impact of RA on the Wnt signaling pathway is probably crucial to this process [4]
Arthritis was induced with an intraperitoneal (i.p.) injection of 20 mg mannan suspended in 0.2 ml PBS, which induces the arthritis through the complement system [20]
Summary
Local bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation. It is well known that patients with rheumatoid arthritis (RA) develop both local bone erosions and systemic osteoporosis. Local bone erosion in RA is mediated through bone resorption by the osteoclast at the cartilage-pannus junction [1]. Treatment of RA has improved considerably over the last decade, but even with the best current therapies, a number of patients still have progression of erosive bone changes in the joints [8]. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. Treatment strategies that directly target bone are relevant
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