The effects of zoledronic acid and dexamethasone on osseointegration of endosseous implants: histological and histomorphometrical evaluation in rats.

BACKGROUND: Bisphosphonates are a widely used class of drugs that prevent bone loss. Several side effects related to bisphosphonate therapy have been reported, including osteonecrosis of the jaws associated with invasive dental procedures and implants placement. OBJECTIVES: To evaluate the influence of intravenous nitrogen-containing BPs in combination with or without dexamethasone on osseointegration of titanium implants placed in an animal model. METHODS: Twenty-seven male Wistar rats were divided into three groups: group 1 was treated solely with zoledronic acid, group 2 was treated with zoledronic acid and dexamethasone, and group 3 did only receive saline solution injections. Two endosseous implants were placed in each tibia, and three animals from each group were sacrificed at postoperative times of seven, 14, and 28 days. Non-decalcified sections were observed with light microscopy for histological and histomorphometrical analyses. RESULTS: Histomorphometrical analysis using the animals and the implants as unit of measurement revealed no statistically significant difference regarding bone-implant contact and bone density among the three groups. Histological observation revealed that zoledronic acid-treated animals in combination with or without dexamethasone showed expressive less bone remodeling activity at 14 and 28 days after implants placement, compared with control specimens. CONCLUSIONS: The studied bisphosphonate regimens did not interfere with the osseointegration of the implants, cortical, or medular bone deposition, but a possible lack of bone remodeling of the original cortical bone may affect long-term osseointegration.

Intracellular sAPP retention in response to Abeta is mapped to cytoskeleton-associated structures.

Amyloid beta (Abeta) contributes to neurodegeneration in Alzheimer's disease and provides a close association between molecular events and pathology, although the underlying molecular mechanisms are unclear. In the work described here, Abeta did not induce amyloid precursor protein (APP) expression, but APP processing/trafficking was markedly affected. In COS-7 cells, Abeta provokes retention of intracellular sAPPalpha (isAPPalpha). Intracellular holo-APP levels remain unchanged, and extracellular total sAPP increases, although extracellular sAPPalpha alone was not altered significantly. In primary neuronal cultures and PC12 cells, isAPP also increased, but this was mirrored by a decrease in extracellular total sAPP. The isAPP retention was particularly associated with the cytoskeletal fraction. The retention "per se" occurred in vesicular-like densities, negative for a C-terminal antibody and strongly positive for the 6E10 antibody, clearly showing abnormal intracellular accumulation of sAPPalpha in response to Abeta. Our data support a dynamic model for intracellular retention of sAPPalpha as an early response to Abeta exposure. Particularly noteworthy was the observation that removal of Abeta reversed the isAPP accumulation. Mechanistically, these findings disclose an attractive physiological response, revealing the capacity of cells to deal with adverse effects induced by Abeta.