Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats.

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

Differences in accelerated tooth movement promoted by recombinant human parathyroid hormone after mandibular ramus osteotomy.

INTRODUCTION: This study investigated the effects of different doses of parathyroid hormone (PTH) on orthodontic tooth movement after mandibular ramus osteotomy and the associated dose-response relationship. METHODS: One-hundred twenty rabbits were divided into 2 experimental groups (A and B) and 2 control groups (control group and negative control group). An experimental model of mandibular ramus osteotomy with installation of an orthodontic tooth movement device was established in groups A and B and the control group. After surgery, groups A and B received intermittent subcutaneous injections of PTH, 20 and 40 µg/kg, respectively, and the control group received injections of normal saline solution. The negative control group underwent installation of the orthodontic tooth movement device without mandibular ramus osteotomy and received normal saline solution after surgery. Changes in expression of RANKL and RUNX2 in the periodontal tissues of the first molars were evaluated by means of immunohistochemical analysis and quantitative fluorescence polymerase chain reaction. RESULTS: Movement of the first molars was more rapid in group B than in group A in the 21 days after surgery. Significantly higher RANKL mRNA levels and lower RUNX2 mRNA levels were detected on the compression side of the periodontal tissues in groups A and B than in the control groups. There was a significant difference in RANKL and RUNX2 expression levels between group B and the control groups at all time points. CONCLUSIONS: Mandibular ramus osteotomy combined with high-dose PTH can increase catabolism on the compressed periodontal tissues, thereby accelerating remodeling of periodontal bone and promoting orthodontic tooth movement after surgery.

An Examination of Differences in the New Bone Formation Promoted by Different Doses of Recombinant Human Parathyroid Hormone during Mandibular Distraction Osteogenesis.

BACKGROUND: The administration of different doses of parathyroid hormone to promote mandibular distraction osteogenesis remains unclear. The objective of the present study was to examine the effects of recombinant human parathyroid hormone on new bone formation during mandibular distraction osteogenesis and to investigate the dose-effect relationship associated with this phenomenon. METHODS: A total of 45 rabbits were used to establish the mandibular distraction osteogenesis model. The rabbits were divided into a control group (that received a subcutaneous injection of 1 ml of saline every other day) and experimental groups A, B, C, and D (that received subcutaneous injections of 10, 20, 30, and 40 µg/kg of recombinant human parathyroid hormone, respectively, every other day). On days 1, 7, and 14 of the consolidation period after the distraction had been completed, new bone in the distraction region was examined through histomorphometric investigation and bone mineral density testing. RESULTS: On days 1, 7, and 14 of the fixation period, the number of osteoblasts, trabecular bone area, and bone mineral density were greater in each experimental group than in the control group. On day 1 of the consolidation period, group C featured the highest average number of osteoblasts. On day 14 of the consolidation period, group C exhibited the highest bone mineral densities and largest trabecular bone areas. CONCLUSIONS: Intermittent subcutaneous injections of recombinant human parathyroid hormone can promote new bone formation during mandibular distraction osteogenesis. Different doses of recombinant human parathyroid hormone promoted mandibular distraction osteogenesis to differing extents.

An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone.

PURPOSE: Parathyroid hormone (PTH) is a major regulator of bone metabolism. Various animal studies and clinical trials have addressed the treatment of osteoporosis and fracture healing with the intermittent administration of PTH, whereas few studies have investigated the effects of PTH on mandibular defect repair. This study sought to examine the feasibility of using recombinant human PTH (rhPTH) to promote the repair of mandibular defects and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. MATERIALS AND METHODS: A mandibular defect model was established using Japanese white rabbits. The experimental animals were randomly divided into a control group that received postoperative subcutaneous injections of normal saline on alternate days and an experimental group that received postoperative subcutaneous injections of rhPTH 25 µg on alternate days. The experimental animals were sacrificed at 1, 2, 3, and 4 weeks after the operation to perform x-ray imaging and bone histomorphometric examinations of the defect areas. Changes in serum levels of bone-specific alkaline phosphatase (bALP) and osteoprotegerin (OPG) over time were examined. RESULTS: Compared with the control group, the experimental group exhibited newly generated bone matrix in the mandibular defect area at earlier stages. In the experimental group, the bone trabeculae were arranged in an orderly manner, and uniform calcification was observed. Marked hyperplasia of osteoblasts was observed in the new bone tissue of the experimental group, but significantly less hyperplasia of osteoblasts was observed in the control group. In the 2 groups, the average serum bALP and OPG levels increased after the operation and then gradually decreased. In the experimental group, levels of bALP and OPG at 1 week and 2 weeks after the operation were significantly different from preoperative levels. In the control group, the OPG level at 2 weeks after the operation was significantly different from the preoperative OPG level. A comparison of serum bALP and OPG levels at each examined time point showed no significant difference between the 2 groups. CONCLUSION: The intermittent subcutaneous injection of rhPTH 25 µg/day promotes the healing of mandibular defects in rabbits. The application of rhPTH may facilitate mandible regeneration by increasing quantities of osteoblasts, accelerating bone turnover metabolism, and upregulating OPG levels.

[Reverse-engineering-based quantitative three-dimensional measurement of facial swelling after administration of Yunnan Baiyao following orthognathic surgery].

OBJECTIVE: To evaluate the effects of perioperative oral administration of Yunan Baiyao on reduction of postoperative facial swelling following bimaxillary orthognathic surgery. METHODS: Patients scheduled for Le Fort I osteotomies and bilateral sagittal split ramus osteotomies were enrolled in the prospective, randomized, double-blind, placebo-controlled clinical study. Patients were orally administrated with Yunnan Baiyao capsules or placebo capsules before 3 days of operation and 5 days post-operation. Three-dimensional face images were recorded with OKIO-SC-400 Scanning System in 40 patients at pre-operation, postoperatively 3 day, 1 week and 1 month. Facial scans from different time periods were registrated to same coordinates and overlaid onto the baseline facial scan. 3D and 2D model deviations were performed with reverse engineering software to compare the differences between each two models and to quantitatively determine the reductions in facial swelling. RESULTS: There were 18 patients in Yunnan Baiyao group and 22 patients in control group. The severe swelling region was in the cheek, followed by the upper and lower lip. The average reduction of swelling thickness in Yunnan Baiyao group and control group from 3 day to 1 week postoperative was 3.6 mm and 2.3 mm respectively; there was significant difference between the two groups. Significant differences were also found in percentage changes of facial morphology from 3 day to 1 week postoperative (49.0% and 38.3% respectively). There were no significant changes in facial volumes of swelling between the two groups. CONCLUSIONS: Perioperative oral administration of Yunnan Baiyao capsules can effectively reduce the magnitude of facial swelling in bimaxillary orthognathic surgery. Yunnan Biayao has efficacy of anti-inflammatory response.

[Prophylactic administration of Yunnan Baiyao capsule reduces intra-operative blood loss in orthognathic surgery].

OBJECTIVE: To evaluate the haemostatic efficacy and safety of prophylactic oral administration of Yunan Baiyao capsules on reduction of blood loss in bimaxillary orthognathic surgery. METHODS: Eighty-seven patients scheduled for Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) were enrolled in the prospective, randomized, double-blind, placebo-controlled clinical study. Forty-three patients took prophylactic oral administration of Yunnan Baiyao capsules 3 days before operation, and 44 patients without Yunnan Baiyao administration served as control. The intraoperative blood loss during Le Fort I osteotomy and bilateral sagittal split ramus osteotomy was estimated and the safety of Yunnan Baiyao capsules was evaluated. RESULTS: The total blood loss in the Yunnan Baiyao group (330.5 +/- 134.4) ml was significantly lower than that of the control group (420.3 +/- 175.9) ml. The blood loss of Le Fort I osteotomy in the Yunnan Baiyao group (154.9 +/- 84.3) ml was also significantly lower than that of the control group (203.8 +/- 98.1) ml. The mean blood loss of BSSRO in the Yunnan Baiyao group was also lower than that of the control group, but the differences was not significant. The post-operative fibrinolysis was in the same level in both groups. Thromboemblic events or other side effects were not observed in this clinical trial. CONCLUSIONS: Prophylactic oral administration of Yunnan Baiyao capsules can effectively reduce the intra-operative blood loss in bimaxillary orthognathic surgery. Yunnan Baiyao capsule are an effective and safe haemostatic traditional Chinese medicine.

[Evaluation of Yunnan Baiyao capsules for reducing postoperative swelling after orthognathic surgery].

OBJECTIVE: To evaluate the effects of Yunnan Baiyao capsules on facial swelling and anti-inflammatory response after orthognathic surgery. METHODS: 87 patients scheduled for Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) and genioplasty were randomly divided into 2 groups: experiment roup (n = 43) given with Yunnan Baiyao capsules orally 4 days before operation once daily and then via nasal feeding tube after operation once a day for 5 days, and placebo group given with placebo capsules. Antibiotic was routinely given to both groups. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and IL-1 were quantified on postoperative days 1, 2, 3, and 5. Degrees of facial swelling were evaluated on postoperative days 3, 5, and 7. RESULTS: Peak CRP and cytokines levels were reached on the first postoperative day in both groups, and the the variables decreased. The serum concentrations of CRP and IL-6 in the Yunan Baiyao group were lower than those in the control group. The CRP levels on the postoperative day 2, 3 and 5 of the experiment group were all significantly lower than those of the placebo group, and the IL-6 level on the second postoperative day of the experiment group was significantly lower than that of the placebo group. CONCLUSION: Perioperative administration of Yunnan Baiyao capsules can reduce the magnitude of inflammatory response and facial swelling after orthognathic surgery. Yunnan Baiyao capsule has efficacy of anti-inflammatory response.

Effect of nerve growth factor and Schwann cells on axon regeneration of distracted inferior alveolar nerve following mandibular lengthening.

OBJECTIVE: To study the effect of nerve growth factor (NGF) and Schwann cells on axon regeneration of the inferior alveolar nerve following mandibular lengthening with distraction osteogenesis. METHODS: Unilateral mandibular osteodistraction was performed in 9 healthy adult male goats with a distraction rate of 1 mm/d. Every 3 goats were killed on days 7, 14 and 28 after mandibular lengthening, respectively. The inferior alveolar nerves in the distraction callus were harvested and processed for ultrastructural and NGF immunohistochemical study. The inferior alveolar nerves from the contralateral side were used as controls. RESULTS: On day 7 after distraction, axon degeneration and Schwann cell proliferation were observed, and very strong staining of NGF in the distracted nerve was detected. On day 14 after distraction, axon regeneration and remyelination were easily observed, and NGF expression started to decline. On day 28 after distraction, the gray scale of NGF immunoreactivity recovered to the normal value and the Schwann cells almost recovered to their normal state. CONCLUSIONS: Gradual mandibular osteodistraction can result in mild or moderate axon degeneration of the inferior alveolar nerve. Nerve trauma may stimulate the proliferation of Schwann cells and promote the synthesis and secretion of NGF in the Schwann cells. Schwann cells and NGF might play important roles in axon regeneration of the injured inferior alveolar nerve following mandibular lengthening.