Monobloc Le Fort III Distraction Osteogenesis for Correction of Severe Fronto-orbital and Midface Hypoplasia in Pediatric Crouzon Syndrome.

In severe syndromic craniosynostosis, distraction osteogenesis (DO) provides superior segmental advancement and allows progressive clinical monitoring to ensure that adequate skeletal expansion is achieved. We report two cases of Crouzon syndrome involving a 3-year-old boy and a 4-year-old girl, who were both treated with monobloc Le Fort III DO using a combination of external and internal distraction devices (Synthes, Oberdorf, Switzerland) to treat severe orbital proptosis and obstructed nasopharyngeal airway secondary to severe hypoplastic craniofacial skeletal components. Their skeletal segments were advanced in daily increments by 27 mm and 23 mm, respectively. Results at 18 months postoperatively showed successful outcomes, as evidenced by adequate eye protection, tracheostomy tube decannulation following objective evidence of patent nasopharyngeal airway, and acceptable facial appearance. Monobloc Le Fort III DO using a combination of external and internal devices produces favorable functional and clinical outcomes for the treatment of severe orbital and airway discrepancy in Crouzon syndrome.

A Rare Orbital Complication of Eye Exodeviation With Limited Abduction During Monobloc Le Fort III Distraction Osteogenesis.

Monobloc Le Fort III distraction osteogenesis allows superior skeletal advancement in treating severe syndromic craniosynostosis. We report a rare orbital complication in a 3-year-old boy with Crouzon syndrome who developed right-eye exodeviation with limited abduction during the intradistraction period following this surgery. Images from a computed tomography scan confirmed direct impingement of the distracted right lateral orbital wall to the lateral rectus muscle. The impingement was surgically relieved via lateral orbital wall osteotomy. Ten months postdistraction, a review showed normal eye movement. A lateral orbital osteotomy cut for a monobloc Le Fort III distraction should be designed near the rim to prevent this complication.

Quantitative analysis of titanium-induced artifacts and correlated factors during micro-CT scanning.

OBJECTIVES: To investigate the impact of cover screw, resin embedment, and implant angulation on artifact of microcomputed tomography (micro-CT) scanning for implant. MATERIALS AND METHODS: A total of twelve implants were randomly divided into 4 groups: (i) implant only; (ii) implant with cover screw; (iii) implant with resin embedment; and (iv) implants with cover screw and resin embedment. Implants angulation at 0°, 45°, and 90° were scanned by micro-CT. Images were assessed, and the ratio of artifact volume to total volume (AV/TV) was calculated. A multiple regression analysis in stepwise model was used to determine the significance of different factors. One-way ANOVA was performed to identify which combination of factors could minimize the artifact. RESULTS: In the regression analysis, implant angulation was identified as the best predictor for artifact among the factors (P < 0.001). Resin embedment also had significant effect on artifact volume (P = 0.028), while cover screw had not (P > 0.05). Non-embedded implants with the axis parallel to X-ray source of micro-CT produced minimal artifact. CONCLUSIONS: Implant angulation and resin embedment affected the artifact volume of micro-CT scanning for implant, while cover screw did not.

Dose-dependent effect of radiation on titanium implants: a quantitative study in rabbits.

OBJECTIVES: The aim of the study was to investigate the dose-dependent effect of radiation on dental implant stability and osseointegration using a series of quantitative analyses. MATERIAL AND METHODS: Six rabbits were randomly assigned to 15 and 30 Gy radiation groups. Each rabbit received radiation at the tibial and femoral metaphyseal region of left hind leg. The right leg was used as control. Implant surgery was performed on tibial and femoral metaphyses after 1 week. Totally 24 implants were inserted. The animals were killed at postoperative week four. Implant stability was measured using resonance frequency analysis. Ratio of bone volume to total volume (BV/TV), rate of bone growth, and bone-to-implant contact (BIC) were assessed using micro-computed tomography (micro-CT), fluorochrome labeling analysis, and histomorphometric analysis, respectively. RESULTS: After 4 weeks of healing, all implants were integrated (n = 6). Implant stability was significantly compromised by 15 Gy (P = 0.010) and 30 Gy (P = 0.025) of radiation. Radiation decreased BV/TV, and the significant effect was detected at the dose of 15 Gy (P = 0.008) and 30 Gy (P < 0.001). Bone growth in osseointegration was impaired by radiation. In 15 Gy group, the radiation side showed significant lower rate of bone growth than the control side at week 3 (P = 0.001), while the undistinguishable signals on 30 Gy radiation side suggested the low rate of new bone formation at each time point. Histomorphological BIC had no significant difference between 15 Gy control side and 15 Gy radiation side. 30 Gy radiation side showed a significantly lower BIC than 30 Gy control side (P < 0.001) as well as 15 Gy radiation side (P < 0.001). CONCLUSIONS: Implant stability and osseointegration were compromised by radiation. Radiation compromised osseointegration in a dose-dependent manner.

Recording of natural head position using stereophotogrammetry: a new technique and reliability study.

The purpose of this study was to develop a technique to record physical references and orient digital mesh models to a natural head position using stereophotogrammetry (SP). The first step was to record the digital mesh model of a hanging reference board placed at the capturing position of the SP machine. The board was aligned to true vertical using a plumb bob. It also was aligned with a laser plane parallel to a hanging mirror, which was located at the center of the machine. The parameter derived from the digital mesh model of the board was used to adjust the roll, pitch, and yaw of the subsequent captures of patients' facial images. This information was valid until the next machine calibration. The board placement was repeatable, with standard deviations less than 0.1° for pitch and yaw angles and 0.15° for roll angles.

Alveolar distraction osteogenesis for dental implant rehabilitation following fibular reconstruction: a case series.

OBJECTIVE: Alveolar distraction osteogenesis (ADO), a novel bone augmentation technique, is gaining acceptance in restoring the vertical bone discrepancy between the transplanted graft and the residual alveolar bone after mandibular reconstruction. This case series presents the outcomes of ADO in fibula-reconstructed mandibles rehabilitated with dental implants, with an emphasis on clinical indications, surgical protocol, clinical outcomes, histologic evidence, and complications. MATERIALS AND METHODS: Five patients underwent fibula distraction procedures after undergoing mandibular reconstruction with a vascularized fibula bone graft. The indication for the application of ADO was for the correction of the vertical discrepancy between the top of the reconstructed fibula and the adjacent alveolar crest to achieve adequate vertical bone height before implant placement. RESULTS: The mean vertical bone height achieved was 13.58 mm. Twenty-two dental implants were placed in 5 patients. All patients were rehabilitated with implant-supported prostheses. Bone biopsies showed the distracted area was filled with newly formed, bony trabeculae between the transported fibula and the basal segments. The most common complication was transient infection around the distractor rod. CONCLUSIONS: ADO can be performed on fibula-reconstructed mandibles to achieve the restoration of alveolar height, which then can be rehabilitated with dental implant-supported prostheses. The procedure has a minor risk of infection associated with the distractor rod, which does not compromise the bone regeneration from distraction. Patients with mandibles reconstructed with fibulas can attain dental implant rehabilitation with ADO, achieving good esthetic and occlusal outcomes.

Soft tissue changes from maxillary distraction osteogenesis versus orthognathic surgery in patients with cleft lip and palate--a randomized controlled clinical trial.

PURPOSE: The objective of this randomized controlled clinical trial was to compare the soft tissue changes after maxillary advancement using conventional orthognathic surgery (CO) and distraction osteogenesis (DO) in patients with cleft lip and palate (CLP). MATERIALS AND METHODS: The study group of 39 CLP patients with maxillary hypoplasia underwent either CO or DO with 4 to 10 mm of maxillary advancement. Lateral cephalographs were taken preoperatively and postoperatively at regular intervals. A series of skeletal, dental, and soft tissue landmarks was used to evaluate the changes in the soft tissue and the correlation of hard and soft tissue changes and ratios. RESULTS: Significant differences were found between the CO and DO patients at A point in both maxillary advancement and downgrafting in the early follow-up period. On soft tissue landmarks of pronasale, subnasale, and labial superius, significant differences were found between the 2 groups at 6 months postoperatively only with maxillary advancement. There was better correlation of hard and soft tissue changes with maxillary advancement. The nasal projection was significantly different between the 2 groups at the early and intermediate period. There was much more consistent hard to soft tissue ratios in maxillary advancement with DO than with CO. CONCLUSIONS: Both CO and DO can induce significant soft tissue changes of the upper lip and nose, particularly with maxillary advancement. DO generates more consistent hard to soft tissue ratios.

Coronectomy of the lower third molar is safe within the first 3 years.

PURPOSE: There is no long-term evaluation on the safety of coronectomy of the lower third molar. The aim of this study was to investigate the 3-year morbidity of coronectomy of the lower third molars and to monitor the behavior and migration pattern of the retained roots after coronectomy. MATERIALS AND METHODS: This was a prospective cohort study. Patients with lower third molars with specific radiographic sign(s) showing proximity of the roots to the inferior alveolar nerve who underwent coronectomy in a previous randomized clinical trial were reviewed postoperatively in the first week and the third, sixth, 12th, 24th, and 36th months. The morbidities of infection, pain, root eruption, reoperation to remove the root, and the development of any pathology were recorded. The pattern of any root migration was analyzed. RESULTS: Ninety-eight patients (35 men and 63 women; mean age, 25.7 yrs; standard deviation, 7.9 yrs) with 135 coronectomies completed the 36-month review. None presented with infection or pain from the postoperative third month onward. Root eruption causing sensitivity occurred in 3% (4/135) of the sample and the erupted roots were removed. None of the reoperated cases presented with a postoperative inferior alveolar nerve deficit. No pathology developed in any of the retained roots after coronectomy. Root migration was noted in most cases in the first 12 months, and all roots stopped migrating from the 24th month onward. The mean root migration at 36 months was 2.8 mm (standard deviation, 1.4 mm). CONCLUSIONS: This study confirms that retained roots after coronectomy in the lower third molars produce no complications in terms of infection, pain, or the development of pathologies within the first 3 years. Root eruption can occur in a very small percentage of patients and may require reoperation to remove the root.

Treatment modalities of neurosensory deficit after lower third molar surgery: a systematic review.

PURPOSE: To conduct a systematic review to answer the clinical question, "What are the available treatment modalities and their outcomes of neurosensory deficit after lower third molar surgery?" MATERIALS AND METHODS: A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of 3 key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the 6 predetermined criteria were chosen to enter the final review. The various treatment modalities and their outcomes of neurosensory deficit after lower third molar surgery, in the selected studies in the final review, were analyzed. RESULTS: Ten articles entered the final review. Six treatment modalities of lingual nerve or inferior alveolar nerve deficit after lower third molar surgery were identified. External neurolysis, direct suturing, autogenous vein graft, and a Gore-Tex tube as a conduit were the 4 surgical treatments. Significant improvement after surgical treatment ranged from 25% to 66.7%. Acupuncture and low-level laser therapy were 2 available nonsurgical treatment modalities that were found to have produced significant improvement in sensation after treatment in more than 50% of subjects. There was insufficient information to determine the best timing of treatment of nerve injury after third molar surgery. CONCLUSIONS: Four surgical treatments and 2 nonsurgical treatments were identified in the management of neurosensory disturbance after lower third molar surgery. Most treatments showed an improvement in sensation but the outcomes were variable. Complete recovery was uncommon in all kinds of available treatments.

Treatment of irradiated mandibles with mesenchymal stem cells transfected with bone morphogenetic protein 2/7.

PURPOSE: The study aimed to evaluate whether mesenchymal stem cells transfected with bone morphogenetic protein (BMP) 2/7 could increase bone regeneration after radiotherapy using a rabbit model of mandibular distraction osteogenesis. MATERIALS AND METHODS: Twelve rabbits were randomly assigned to the sham control, radiotherapy control, nontransfected mesenchymal stem cells (MSCs), and MSCs transfected with BMP-2/7 groups. All rabbits, except those in the sham control group, received preoperative radiation of 9 Gy for 5 fractions. One month after radiotherapy, all rabbits underwent unilateral mandibular distraction at a rate of 0.9 mm/d for 11 days. At the end of active distraction, MSCs combined with bovine collagen were injected into the distraction zone. After 4 weeks of consolidation, the mandibular samples were collected and subjected to radiographic, microcomputed tomographic, and histologic examinations. RESULTS: By radiographic examination, animals injected with nontransfected MSCs or MSCs encoding BMP-2/7 exhibited more bone formation than the control groups. Histologic examination showed that the group with MSCs encoding BMP-2/7 had a more mature medullary cavity than the nontransfected MSCs group. CONCLUSIONS: MSCs encoding BMP-2/7 can increase bone healing in irradiated mandibular bone.

Influence of low-dose nicotine on bone healing.

BACKGROUND: Nicotine at a low concentration was suggested as a new topical drug for clinical application. It has been reported to be capable of enhancing skin wound healing. This study was designed to assess the effect of nicotine administration at a low dose on bone regeneration using a rabbit model of mandibular distraction osteogenesis. METHODS: Twenty New Zealand white rabbits were randomly assigned to nicotine group and control group. A total of 0.75 g, 60-day time release, nicotine pellets or placebos were implanted in the neck subcutaneous tissue of the rabbits. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Five animals in each group were killed on week 2 and week 4 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, and immunohistochemical analysis. RESULTS: Nicotine at low dose showed no significant effect on the expression of bone morphogenetic protein-2 and on the radiodensity of bone regeneration. However, the delayed bone healing was detected in the nicotine group by histologic examination. CONCLUSIONS: These findings imply a potential risk of compromised bone healing in patients taking nicotine medication. Further clinical studies are necessary to assess the risk of nicotine medication on reconstructive surgery.

Correlation of radiographic signs, inferior dental nerve exposure, and deficit in third molar surgery.

PURPOSE: To identify the specific radiographic signs on orthopantomograms that are positive predictors of intraoperative inferior dental nerve (IDN) exposure and postoperative IDN deficit in lower third molar surgery. MATERIALS AND METHODS: A prospective clinical cohort of patients with lower third molars with specific radiographic signs showing a close proximity of the roots to the IDN who underwent total excision at our center from June 2006 to June 2008 were recruited as the study group. The prevalence of intraoperative IDN exposure and postoperative IDN deficit were recorded. The correlations between the various radiographic signs and the prevalence of IDN exposure and deficit were analyzed. The prevalence of IDN deficit in the sample was compared with an age-, gender-, and operator experience-matched control group of patients who had undergone lower third molar surgery without any of the radiographic signs present. RESULTS: Patients with a total of 178 lower third molars with 1 or more of the specific radiographic signs present were recruited as the study group. The prevalence of IDN deficit in the study group (5.1%) was significantly greater than that in the control group (0.56%; P = .01). In the study group, darkening of root and displacement of the inferior dental canal by the root were radiographic signs significantly related to IDN exposure (P = .001 and P = .019, respectively). Darkening of the root was the only sign significantly related to a postoperative IDN deficit (P = .016). When 2 or more radiographic signs were present, the risk of a postoperative IDN deficit was significantly increased (P = .001). CONCLUSIONS: Darkening of the root and displacement of the inferior dental canal by the root were positive predictors of intraoperative IDN exposure. Darkening of the root or the presence of 2 or more radiographic signs were positive predictors of a postoperative IDN deficit.

Comparison of distraction osteogenesis versus costochondral graft in reconstruction of temporomandibular joint condylectomy with disc preservation.

PURPOSE: This study compared transport distraction with costochondral graft in the reconstruction of temporomandibular joint (TMJ) with disc preservation. MATERIALS AND METHODS: Bilateral condylectomies with disc preservation were conducted in 12 adult goats. Transport distraction of the mandibular ramus was performed on 1 side and costochondral graft on the other side. Jaw movements, TMJ healing, and condylar remodeling were assessed by clinical, radiologic, and histologic examinations. RESULTS: Transport distraction and costochondral graft established a new condyle separating from the preserved disc with a joint space. Both techniques showed no significant difference in ankylosis scores up to 24 weeks. Signs of calcification were not noted in the transport distraction or costochondral graft side. No significant change of maximal jaw movements was found at any time point from 2 to 24 weeks. CONCLUSIONS: Distraction osteogenesis is an effective reconstruction method for TMJ reconstruction. No significant difference between these 2 techniques in reconstruction of the TMJ was noted.

Expression of bone morphogenetic protein, vascular endothelial growth factor, and basic fibroblast growth factor in irradiated mandibles during distraction osteogenesis.

PURPOSE: The present study evaluated the expression of bone morphogenetic proteins (BMPs)-2, -4, -7, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in irradiated mandibles during distraction osteogenesis. MATERIALS AND METHODS: A total of 24 rabbits were randomly assigned to the control and experimental groups. Each rabbit in the experimental group underwent preoperative radiation to 9 Gy in 5 fractions. After 1 month, all rabbits underwent osteotomy and distraction osteogenesis with 7 days of latency. Three rabbits in the control and experimental groups were killed at day 7 (end of the latency period), day 12 (middle of active distraction), day 18 (end of active distraction), and day 25 (1 week after consolidation). The specimens were used for immunohistochemical staining and real-time polymerase chain reaction analysis. RESULTS: Histologically, at day 25, cortical bone formation was much better in the control group than in the radiotherapy group. In the radiotherapy group, the bone spicules were aligned in the direction of tension stress. At day 12, the expression of BMP-2, -4, and -7 was elevated in the radiotherapy group compared with the control group. At day 25, the expression of BMP-2 was significantly greater in the radiotherapy group. At day 7, the expression of bFGF was significantly suppressed in the radiotherapy group. At day 12, the expression of bFGF and VEGF was significantly elevated in the radiotherapy group compared with the control group. At day 25, the expression of VEGF was significantly greater in the radiotherapy group. CONCLUSIONS: The results of our study have shown that radiotherapy changes the expression pattern of BMPs, VEGF, and bFGF.

Effect of platelet-rich plasma on a rabbit model of nicotine-compromised bone healing.

PURPOSE: This study aimed to evaluate the effects of platelet-rich plasma (PRP) on nicotine-compromised bone healing. MATERIALS AND METHODS: Fifteen adult New Zealand white rabbits were implanted with 1.5-g time-release nicotine pellets. Bilateral mandibular distraction osteogenesis was then performed. Autologous PRP was injected into 1 side of the distraction regenerate, whereas physiologic saline solution was injected into the contralateral side as a control. Five rabbits were killed on day 5 of active distraction, on day 11 of active distraction, and in week 2 of consolidation, respectively. RESULTS: In the PRP the platelet enrichment was 14.63 ± 3.081-fold of that in whole blood. Plain radiography and micro-computed tomography assessment showed no significant difference between the PRP injection and control sides. Histologic examination showed more disorganized distraction tissue on the PRP injection side. CONCLUSIONS: PRP injection at an early stage of active distraction does not significantly enhance bone healing in the nicotine-compromised rabbit model of mandibular lengthening.

Quasi-continuous autodriven system with multiple rates for distraction osteogenesis.

INTRODUCTION: For a given rate of distraction a greater frequency of distraction improves bone formation. However, the current distractors used in clinic are activated manually and produces intermittent advancement. METHOD: The authors developed an automatic driver that is capable of producing quasi-continuous distraction at a set of rates of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm/d. Using a customized in vitro experimental system, the function and stability of the autodriven system were tested during loading. RESULTS: The angular displacement of the automatic driver was quite regular while driving a constant torque of 4.268 × 10-(3) kg m. The driving achieved the target speed with the constant torque. CONCLUSIONS: The automatic driven system provides a useful tool to assess the tissue healing at variable distraction rates with quasi-continuous traction. It demonstrates a potential for clinical application to shorten the treatment course of distraction osteogenesis.

Effect of nicotine on gene expression of angiogenic and osteogenic factors in a rabbit model of bone regeneration.

PURPOSE: This study aims to evaluate the influence of nicotine on the gene expression of osteogenic and angiogenic factors in bone regeneration by use of a nicotine-compromised rabbit model of mandibular lengthening. MATERIALS AND METHODS: Thirty adult New Zealand white rabbits were randomly assigned to the nicotine group or the control group. The total nicotine or placebo exposure time for all animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Five animals in each group were sacrificed at day 5, day 11, and day 18, respectively, after commencement of active distraction. The distraction regenerate samples were harvested, and the messenger ribonucleic acid expression of bone transforming growth factor beta(1), platelet-derived growth factor A, and basic fibroblast growth factor was assayed by real-time polymerase chain reaction analysis. RESULTS: The messenger ribonucleic acid expression of transforming growth factor beta(1), platelet-derived growth factor A, and basic fibroblast growth factor was significantly inhibited by nicotine exposure at a variety of time points. CONCLUSIONS: The presence of nicotine inhibited the gene expression of angiogenic and osteogenic factors resulting in compromised bone regeneration.

Bone regeneration after radiotherapy in an animal model.

PURPOSE: The study aimed to evaluate dosage-dependent effects of irradiation on bone regeneration and established a radiation-compromised rabbit model of mandibular distraction osteogenesis. MATERIALS AND METHODS: Twenty-three rabbits were divided randomly into 7 groups. Group A served as the control group, whereas experimental groups B, C, D, E, F, and G received preoperative irradiation at doses of 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0 Gy, respectively, for 5 fractions. After 1 month, all rabbits underwent osteotomy and distraction osteogenesis with 7 days of latency, 11 days of active distraction at a rate of 0.9 mm/d, and 4 weeks of consolidation; rabbit mandibles were subsequently subjected to histologic, radiographic, and micro-computed tomography analysis. RESULTS: With increasing doses of irradiation, bone regeneration was markedly hampered. Radiographically, the high-dose groups (8.5 and 9.0 Gy) presented obscure cortical lines. Histologically, in the 8.5- and 9.0-Gy groups, cortical bones were not completely formed, and in the medullary cavity, there existed a large amount of fibrous tissue. CONCLUSION: Radiotherapy compromises bone regeneration during distraction osteogenesis, and the adverse effect is dose dependent.

Skeletal stability and complications of bilateral sagittal split osteotomies and mandibular distraction osteogenesis: an evidence-based review.

PURPOSE: To provide an evidence-based review comparing the skeletal stability and complications of bilateral sagittal split osteotomies (BSSOs) and mandibular distraction osteogenesis (MDO) in the treatment of mandibular hypoplasia. MATERIALS AND METHODS: A Medline search from January 1957 to December 2007 was performed wherein articles were retrieved on the basis of a set of inclusion and exclusion criteria. Data on mean skeletal stability and complications for the 2 techniques were retrieved from these articles. RESULTS: Based on the articles about stability, patients undergoing BSSO or MDO with an advancement or lengthening between 6 and 10 mm showed a similar mean skeletal relapse of 15.0% and 17.1%, respectively, within postoperative months 6 to 12. Greater skeletal relapse was reported for BSSO patients with high mandibular plane angles compared with normal mandibular plane angle patients (29.6% vs 11.3%). Based on the articles about complications, patients who underwent MDO showed a lower incidence of persistent inferior alveolar nerve disturbance (2.9%) and condylar resorption (1.4%) compared with BSSO patients, in whom the incidence of these conditions was 27.8% and 6.1%, respectively. CONCLUSION: Both BSSO and MDO showed similar relapse rates for mandibular advancements between 6 and 10 mm. Both techniques may also share similar risk factors for skeletal relapse. BSSO has a higher incidence of persistent neurosensory disturbances and condylar resorption than MDO. Randomized controlled trials of these 2 techniques are still lacking.

Changes in blood perfusion and bone healing induced by nicotine during distraction osteogenesis.

Nicotine is the main chemical in cigarettes responsible for the tobacco's pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. The present study aims to evaluate the effects of nicotine on blood perfusion, angiogenesis and bone formation using a rabbit model of mandibular lengthening. Twenty adult New Zealand white rabbits were randomly assigned to the control group and nicotine group. The total nicotine or placebo exposure time for all animals was 7 weeks. After 2- or 4-week of consolidation following osteotomy, 3-day of latency and 11-day of active distraction, the animals were sacrificed and the mandibles were harvested. Blood perfusion and vascularization were evaluated by Laser Doppler monitoring and Collagen IV immunohistochemistry staining respectively. Bone formation was assessed by radiological, histological and immunohistochemical examination. Results showed that nicotine exposure increased microvessel density, whereas inhibited blood flow and bone formation. The expression of bone morphogenetic protein (BMP)-2 in osteoblasts was also decreased. Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.