Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway.

Introduction: In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).

Matrix-Bound Zolzoledronate Enhances the Biofilm Colonization of Hydroxyapatite: Effects on Osteonecrosis.

(1) Background: The aim of this study was to test whether matrix-bound zoledronate (zol) molecules enhanced the oral biofilm colonization of a mineralized matrix, rendering the alveolar bone more susceptible to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures. (2) Methods: We tested the effect of matrix-bound zol on the growth and attachment of (Pg), (Fn) and (Ai), and whether the nitrogen-containing component of zol contributed to such effect. The role of oral bacteria in the induction of osteonecrosis was then tested using an extra-oral bone defect model.

Biochemical and X-ray micro-computed tomographic analyses of critical size bone defects grafted with autogenous bone and mercerized bacterial cellulose membranes salified with alendronate.

Objectives: This study aimed to evaluate the repair of critical-sized bone defects grafted with autogenous bone and mercerized bacterial cellulose membranes (BCm) salified with alendronate (ALN).

Methods: Forty-eight male Wistar rats underwent surgery to create a 5 mm-diameter bone defect in the calvarium. The removed bone was particularized, regrafted into the defect, and covered by a BCm according to the group: control group (CG), simply mercerized BCm; group 1 (G1), negatively charged BCm (BCm-CM) salified with ALN; and group 2 (G2), positively charged BCm (BCm-DEAE) salified with ALN.

Role of dendritic cell-mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw.

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw.

Removal of matrix-bound zoledronate prevents post-extraction osteonecrosis of the jaw by rescuing osteoclast function.

Unlike other antiresorptive medications, bisphosphonate molecules accumulate in the bone matrix. Previous studies of side-effects of anti-resorptive treatment focused mainly on systemic effects. We hypothesize that matrix-bound bisphosphonate molecules contribute to the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Heat generation during removal of an abutment screw fragment from dental implants.

Statement Of Problem: Little information is available on the effect of drilling speed on surrounding bone during the removal of an abutment screw fragment.

Purpose: The purpose of this in vitro study was to compare, in vitro, the peak temperature increase during the removal of fractured abutment screws from implants placed in a porcine mandible, using drilling speeds of 600 or 2000 rpm.

Material And Methods: Twenty 4.

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis.

Removal of pamidronate from bone in rats using systemic and local chelation.

Objectives: Bisphosphonates become adsorbed on hydroxyapatite crystals in the bone matrix. In case of side-effects, stopping the treatment would not affect the bisphosphonates already deposited in bone. This study tests the feasibility of in-vivo targeted removal of bisphosphonates from bone using chelating agents.

Mesenchymal stem cell expression of SDF-1β synergizes with BMP-2 to augment cell-mediated healing of critical-sized mouse calvarial defects.

Bone has the potential for spontaneous healing. This process, however, often fails in patients with comorbidities. Tissue engineering combining functional cells, biomaterials and osteoinductive cues may provide alternative treatment strategies.

Dentate transport discs can be used to reconstruct large segmental mandibular defects.

Purpose: This study tested the use of a dentate transport segment for the reconstruction of a large U-shaped defect in the anterior segment of the canine mandible using a novel curved reconstruction plate. The quality and quantity of bone regenerate formed by dentate versus edentulous transport segments were compared.

Materials And Methods: In 5 adult foxhound dogs, a defect of 70 to 75 mm was created in the canine mandible by excising the mandible anterior to the right and left fourth premolars.

Mesenchymal stem cell expression of stromal cell-derived factor-1β augments bone formation in a model of local regenerative therapy.

Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies.

Biomechanics of the canine mandible during bone transport distraction osteogenesis.

This study compared biomechanical patterns between finite element models (FEMs) and a fresh dog mandible tested under molar and incisal physiological loads in order to clarify the effect of the bone transport distraction osteogenesis (BTDO) surgical process. Three FEMs of dog mandibles were built in order to evaluate the effects of BTDO. The first model evaluated the mandibular response under two physiological loads resembling bite processes.

Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice.

Background: A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used.

Total body irradiation is permissive for mesenchymal stem cell-mediated new bone formation following local transplantation.

Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury.

Effect of metformin on periimplant wound healing in a rat model of type 2 diabetes.

Purpose: To investigate the effects of hyperglycemia and metformin (a popular biguanide antidiabetic) on periimplant healing.

Methods: Thirty-six male rats were assigned to 3 groups: (1) nondiabetic Wistar-Kyoto rats (controls), (2) Goto-Kakizaki (GK) spontaneously diabetic rats (GK group), and (3) GK rats were fed metformin (100 mg/kg body weight per day) in their water for 4 weeks (GK + Met group). The right maxillary first molars were extracted and sites were allowed 1 month to heal.

Low-dose bone morphogenetic protein-2/stromal cell-derived factor-1β cotherapy induces bone regeneration in critical-size rat calvarial defects.

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1β, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1β enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro.

Vascular alterations in the sprague-dawley rat mandible during intravenous bisphosphonate therapy.

Long-term use of intravenous bisphosphonates, such as zoledronic acid (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most cases. To determine the effects of zoledronic acid on the vascular structure of the rat mandible.

Osseointegration of dental implants placed into canine mandibular bone regenerated by bone transport distraction osteogenesis.

Purpose: The purpose of this study was to compare the osseointegration of dental implants placed in canine mandibular bone and in regenerated bone produced by bone transport distraction osteogenesis.

Materials And Methods: Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 40-mm defect was created on one side of the mandible.

Alveolar ridge augmentation for implant fixation: status review.

This literature review was performed to illustrate and compare different alveolar ridge augmentation procedures before dental implant placement. The review was based on clinical and research studies listed in Pubmed. There is not enough evidence to support any single method as gold standard for any given condition, and choice seemed to be based on personal preferences.

Delayed versus immediate reconstruction of mandibular segmental defects using recombinant human bone morphogenetic protein 2/absorbable collagen sponge.

Purpose: To compare the efficiency of recombinant human bone morphogenetic protein 2 (rhBMP2)/absorbable collagen sponge (ACS) in the delayed versus immediate reconstruction of mandibular segmental defects in a canine model.

Methods: We randomized 11 dogs into 2 groups: immediate reconstruction (group 1, n = 6) and delayed reconstruction (group 2, n = 5). A 35-mm osteoperiosteal segmental defect was created on the left side of the mandible.

Difference in soft tissue response between immediate and delayed delivery suggests a new mechanism for recombinant human bone morphogenetic protein 2 action in large segmental bone defects.

The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF).

Architecture and microstructure of cortical bone in reconstructed canine mandibles after bone transport distraction osteogenesis.

Reconstruction of the canine mandible using bone transport distraction osteogenesis has been shown to be a suitable method for correcting segmental bone defects produced by cancer, gunshots, and trauma. Although the mechanical quality of the new regenerate cortical bone seems to be related to the mineralization process, several questions regarding the microstructural patterns of the new bony tissue remain unanswered. The purpose of this study was to quantify any microstructural differences that may exist between the regenerate and control cortical bone.

Biomechanical characteristics of regenerated cortical bone in the canine mandible.

To test the mechanical properties of regenerate cortical bone created using mandibular bone transport (MBT) distraction, five adult male American foxhound dogs underwent unilateral distraction of the mandible with a novel MBT device placed to linearly repair a 30-35 mm bone defect. The animals were sacrificed 12 weeks after the beginning of the consolidation period. Fourteen cylindrical specimens were taken from the inner (lingual) and outer (buccal) plates of the reconstructed mandible and 21 control specimens were removed from the contralateral aspect of the mandible.

Bone regeneration and docking site healing after bone transport distraction osteogenesis in the canine mandible.

Purpose: Bone transport distraction osteogenesis provides a promising alternative to traditional grafting techniques. However, existing bone transport distraction osteogenesis devices have many limitations. The purpose of this research was to test a new device, the mandibular bone transport reconstruction plate, in an animal model with comparable mandible size to humans and to histologically and mechanically examine the regenerate bone.