Periarticular bone alterations in chronic antigen-induced arthritis: free and liposome-encapsulated clodronate prevent loss of bone mass in the secondary spongiosa.

The long-term effects of acutely administered clodronate (free or liposome-encapsulated) on periarticular bone mass and bone turnover were investigated in chronic antigen-induced arthritis (AIA; day 28). Wistar rats were treated intraperitoneally at 3 h and on days 1, 2, and 7 of AIA, with phosphate-buffered saline (PBS; sham), PBS-containing liposomes, free clodronate, or liposome-encapsulated clodronate (cumulative dose, 3.64 mg/animal). In the primary spongiosa (</=1 mm from the growth plate) sham-treated AIA was associated with a significant decrease (-31%) of trabecular bone volume only; this change was not prevented by any treatment. In the secondary spongiosa (>1.25 mm from the growth plate), sham-treated AIA was associated with: (a) a marked significant decrease in trabecular bone volume (-56%); (b) a significant increase of osteoid-covered surface (+135%); and (c) a numerical increase of resorption surface with osteoclasts (+96%). In the secondary spongiosa, free clodronate completely prevented the loss of periarticular bone mass and selectively normalized the parameters of bone formation (i.e., osteoid-covered surface and osteoid-covered surface with osteoblasts). Clodronate liposomes, in addition to these effects, also significantly suppressed bone resorption (i.e., resorption surface covered with osteoclasts). The effects of clodronate liposomes coincided with in vivo targeting of osteoclasts in primary and secondary spongiosa. Thus, low-dose, acutely administered clodronate, both in free and encapsulated forms, exerts an excellent preventive effect on bone loss in the secondary spongiosa of chronic AIA.