Background: Bisphosphonate related osteonecrosis of the jaws (BRONJ) is a severe but

Mg-substituted HA coated surfaces promote osteogenic differentiation of preosteoblasts in vitro and may improve implant osseointegration during the early stages of bone healing compared with pure EDHA coated surfaces.

BACKGROUND AND PURPOSE Bisphosphonate‐related osteonecrosis of the jaw (BRONJ) has been identified as a severe complication of patients previously treated with i.v. bisphosphonates. It has been noted that necrotic bone from BRONJ sites display signs of bacterial infection suggesting that an immune defect may play a role in the pathophysiology of BRONJ. Here, we have examined the effect of two potent bisphosphonates, zoledronate and pamidronate, on neutrophil function, differentiation and survival. EXPERIMENTAL APPROACH The effect of bisphosphonates on chemotaxis, NADPH oxidase activity and neutrophil survival were assessed in vitro using bone marrow‐derived primary neutrophils or in vitro differentiated haematopoetic progenitors from mice. The same parameters and the number of circulating neutrophils were quantified in neutrophils isolated from mice treated in vivo with zoledronate. In vivo recruitment of neutrophils was assessed by sodium periodate‐induced peritonitis. KEY RESULTS Zoledronate and pamidronate inhibited in vitro neutrophil chemotaxis and NADPH oxidase activity in a dose‐dependent manner. In vivo recruitment of neutrophils was also suppressed. Zoledronate did not affect in vitro differentiation of neutrophils but shortened their life span in a granulocyte‐colony stimulating factor‐dependent manner. fMLP‐induced activation of RhoA activity was decreased by zoledronate treatment. CONCLUSIONS AND IMPLICATIONS Our results show that bisphosphonate exposure leads to impaired neutrophil chemotaxis, neutrophil NADPH oxidase activity and reduced circulating neutrophil counts. This work suggests that bisphosphonates have the potential to depress the innate immune system for a prolonged time, possibly contributing to the pathogenesis of BRONJ.

This study evaluated the repair of critical-sized cranial vault defects in thirty New Zealand white rabbits using various allogeneic and alloplastic bone substitutes designed to provide mechanical protection to the brain as well as osteoinductivity. The strategies employed included demineralized bone matrix (DBM), a putty used in combination with a rigid resorbable plating system as a protective covering and calcium phosphate cement (CPC) combined with native partially purified bone morphogenetic protein (BMP). Bilateral critical-sized defects measuring 15 mm in diameter were created in the parietal bones of 30 adult male New Zealand white rabbits. They were divided into three groups with ten animals in each. Group 1 had one defect left unfilled as a control while autogenous bone was placed in the defect on the other side. In Group 2 a rigid resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville, Florida), was placed over both defects to cover them and protect the underlying tissues. The pericranial aspect of one defect was left unfilled while the other defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical, Jacksonville, Florida), placed into one of the defects while the defect on the other side was filled with the same CPC in combination with BMP in a concentration of 25 mg/mL. Bone healing was assessed clinically, radiographically, and histomorphometrically. All unfilled controlled defects, the defects covered with the resorbable Lactosorb membrane and those filled with calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed with DBM putty in combination with the resorbable Lactosorb membrane and calcium phosphate in combination with BMP healed with bone bridging the entire defect. This was obvious radiographically where the defects appeared completely filled with a dense radiopaque tissue. Histological analysis demonstrated that specimens where DBM putty was used in combination with the resorbable Lactosorb membrane had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM particles was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. In the calcium phosphate groups where BMP was added to the bioimplant there was 45.8% new bone formation at 12 weeks. The utilization of a composite consisting of DBM with resorbable Lactosorb membrane or a composite of calcium phosphate cement composite with BMP promoted complete closure of critical-sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone bridging observed with these composites suggests that they could be used to enhance the protection of intracranial contents following craniofacial surgical procedures.

Introduction: While there are a growing number of studies on the effects of medications on orthodontic tooth movement (OTM), only few studies have investigated the role of corticosteroids, despite their widespread use. The aim of the current study was to evaluate the effects of triamcinolone acetonide injection on OTM in a rabbit model. Study design: Sixteen one-month old rabbits were randomly divided into two groups: Eight rabbits had triamcinolone acetonide (1mg/kg/day) administered IM daily for 21 days (test group) while the remaining eight rabbits received no drug (control group). The rabbits in both groups had a tube bonded to the upper central incisors and a stainless steel helical spring was inserted in tube slot to apply 50 cN distal force. After 3 weeks, the rabbits were sacrificed and the distance between mesial corners of incisors was measured. The incisors are associated tissue was processed for histology and the apical and cervical area of the roots evaluated. An observer who was blind to the study groups evaluated the specimens. Results: All appliance-treated incisors in test and control groups showed evidence of tooth movement. The distance between the incisors was significantly greater in the triamcinolone acetonide treated group compared to the control group (P<0.001). Histological examination revealed an increased number of resorption lacunae and decreased number of cuboidal osteoblastic cells around the apical and cervical area of the Incisor roots in the test compared to the control group (P<0.01). Conclusion: Treatment with triamcinolone acetonide is associated with increased tooth movement in rabbits via increased resorptive activity in the alveolar bone.