Contrast between effects of aminobisphosphonates and non‐aminobisphosphonates on collagen‐induced arthritis in mice

Abstract

1 Bisphosphonates (BPs) are inhibitors of bone resorption, and many derivatives have been developed for the treatment of enhanced bone resorption. Aminobisphosphonates (aminoBPs) are particularly potent in this respect. We have shown previously that aminoBPs, such as 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), induce histidine decarboxylase, the enzyme forming histamine, and increase macrophages, granulocytes and osteoclast numbers. Non-aminoBPs do not show this activity. 2 In the present study, an additional aminoBP, cycloheptyl-aminomethylene bisphosphonate (CHAMBP), was shown to have similar properties to AHBuBP suggesting that these actions are common among aminoBPs. 3 In experiments carried out to determine if aminoBPs affect immune responses, we found that CHAMBP and AHBuBP each exacerbated the arthritis induced in mice by the co-injection of type II collagen and an adjuvant, a model for rheumatoid arthritis. In contrast, dichloromethylene bisphosphonate (C12MBP), a typical non-aminoBP, did suppress the arthritis. 4 On the basis of these results, and those obtained previously, we propose that the exacerbating effects of CHAMBP and AHBuBP may be related to their ability to stimulate the synthesis of histamine and to increase macrophages and granulocytes. Conversely, we propose that the suppressive effect of C12MBP on arthritis is related to its cytotoxic action on macrophages or granulocytes.

Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen‐induced arthritis

“…In the context of bisphosphonate studies in experimental arthritis, the suppressive effect of single doses of ZA on focal bone destruction is noteworthy. The earlier-generation bisphosphonates usually reduced markers of increased bone resorption and physiologic bone resorption at the growth plate, although evidence of inhibition of focal bone erosions was not compelling (37)(38)(39)(40)(41)(42). A notable exception was pamidronate, which reduced the size of radiographic bone erosions in spontaneously arthritic TNF␣-transgenic mice to an extent similar to that observed with the TNF inhibitor infliximab (12).…”

Alendronate prevents bone loss and improves tendon‐to‐bone repair strength in a canine model

“…Nitrogen-containing bisphosphonates (such as alendronate) induce various inflammatory reactions via interleukin dependent mechanisms. [27][28][29][30] Bisphosphonate-induced inflammation exacerbates pathologic conditions such as arthritis 31 and atherosclerosis. 32 Blockage of matrix metalloproteinases improves anterior cruciate graft healing in the bone tunnels.…”

Bisphosphonate-Related Osteonecrosis of the Jaw Around Dental Implants

“…Pamidronate and zoledronate administered intravenously to this patient are BPs that incorporate nitrogen. BPs containing nitrogen (NBPs) induce an inflammatory reaction by stimulating cells (Hewit et al 2005;Endo et al 1993;Nakamura et al 1996). NBPs also exist on the surface of gram-negative cell walls, and increase inflammatory reactions to lipopolysaccharide (LPS), which has a strong inflammatory effect (Yamaguchi et al 2000).…”