Abstract
BackgroundActive vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. However, because the direct effects of 1,25-dihydroxyvitamin D3 (1,25(OH) 2D3) on bone formation and resorption are very complex, the net effect of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation should be investigated. Therefore, we examined the influence of 1,25(OH)2D3 therapy on arthritis-induced alterations of periarticular and axial bone as well as disease activity, inflammation and joint destruction in antigen-induced arthritis (AIA) of the rat.MethodsAIA was induced in 20 eight-week-old female Wistar rats. 10 rats without arthritis were used as healthy controls. AIA rats received 1,25(OH)2D3 (0.2 μg/kg/day, i.p., n = 10) or vehicle (n = 10) at regular intervals for 28 consecutive days beginning 3 days before arthritis induction. Bone structure of the secondary spongiosa of the periarticular and axial bone was analyzed using histomorphometry. Parameters of mineralization were investigated using tetracycline labelling. Clinical disease activity, inflammation and joint destruction were measured by joint swelling and histological investigation, respectively.ResultsAIA led to significant periarticular bone loss. 1,25(OH)2D3 treatment resulted in a highly significant increase in trabecular bone volume and bone formation rate in comparison to both vehicle-treated AIA and healthy controls at periarticular (p < 0.01 and p < 0.001, respectively) and axial bone (p < 0.001 and p < 0.001, respectively). In addition, bone resorption was reduced by 1,25(OH)2D3 at the axial bone (p < 0.05 vs. vehicle-treated AIA). Joint swelling as well as histological signs of inflammation and joint destruction were not influenced by 1,25(OH)2D3.ConclusionsThe results of the study indicate a marked osteoanabolic effect of 1,25(OH)2D3 presumably due to a substantial increase in mineralization. Thus, 1,25(OH)2D3 may be an effective osteoanabolic treatment principle to antagonize the inflammation-associated suppression of bone formation in rheumatoid arthritis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-345) contains supplementary material, which is available to authorized users.
Highlights
Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment
The finding that the knockout of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that maintains the cellular defence against oxidative stress, in mice with antibodyinduced arthritis was associated with an increase in cartilage destruction and with a high number of spontaneous fractures underlines the importance of reactive oxygen species for bone damage in arthritis models [12]
To determine the net effect of 1,25(OH)2D3 on bone and inflammation, we investigated the influence of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation at periarticular and axial bone as well as on inflammatory disease activity in antigen-induced arthritis (AIA) of the rat, a T cell-dependent model of Rheumatoid arthritis (RA) [36,37]
Summary
Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. The finding that the knockout of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that maintains the cellular defence against oxidative stress, in mice with antibodyinduced arthritis was associated with an increase in cartilage destruction and with a high number of spontaneous fractures underlines the importance of reactive oxygen species for bone damage in arthritis models [12]. Based on these pathogenetic mechanisms, which are often only incompletely suppressed by immunosuppressive therapy, adjuvant treatment of RA with substances, that are potentially able to prevent bone loss, is of particular interest. To determine the net effect of 1,25(OH)2D3 on bone and inflammation, we investigated the influence of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation at periarticular and axial bone as well as on inflammatory disease activity in antigen-induced arthritis (AIA) of the rat, a T cell-dependent model of RA [36,37]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
