Different effects of three bisphosphonates on nitric oxide production by macrophages

Reduction of instability-induced bone resorption using bisphosphonates: High doses are needed in rats

“…The mechanisms by which clodronate and alendronate affect the osteoclast differ, and some studies suggest that clodronate has an anti-in ammatory effect, but alendronate has some pro-in ammatory effects (Makkonen et al 1996). However, our ndings with this model do not permit us to draw any conclusions regarding such differences.…”

“…This may explain why nitrogen-containing bisphosphonates reduce osteoclastic activity associated with normal bone remodeling to a greater extent. On the other hand, some studies suggest that the bisphosphonates that resemble the pyrophosphate group have anti-in ammatory effects, while aminobisphosphonates have some pro-in ammatory effects (Makkonen et al 1996).…”

Bisphosphonates: Mechanisms of Action

“…Pamidronate, however, increases the production of IL-6 (205). Clodronate and pamidronate, but not alendronate, also decrease the production of nitric oxide and the expression of inducible nitric oxide synthase in the RAW 264 cells (206). When clodronate is encapsulated into liposomes, its effect is increased while that of pamidronate is decreased.…”

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

“…25 The effects of free DNTP on interleukin-6 (IL-6) and nitric oxide (NO) from bacterial lipopolysaccharide (LPS)-induced RAW 264 cells was studied as previously described. 26,27,30 In brief, the cells were plated on 96-well plates (2 × 10 5 cells/well) and allowed to adhere for 2 h. Then, the cells were treated with various concentrations of DNTP (1-1000 µM) overnight. The cells were washed free of drug, incubated with LPS at 10 µg/mL for an additional 24 h, and the cell supernatants were collected and assayed for IL-6 30 and NO.…”

“…9 Previous studies demonstrated the effects of gem bisphosphonates such as etidronate, clodronate, and the nitrogen-containing pamidronate. [25][26][27] Stock solutions of DNTP and PiBP were prepared by dissolving the drugs in deionized water at a concentration of 60 mM. The pHs of the solutions were adjusted to 7.2 with sodium bicarbonate powder.…”