Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model.

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Cobalt-Doped Mesoporous Silica Coated Magnetic Nanoparticles Promoting Accelerated Bone Healing in Distraction Osteogenesis.

Introduction: Large bone abnormalities are commonly treated using distraction osteogenesis (DO), but it is not suitable for a long-term application; therefore, there is an urgent need for adjuvant therapy that can accelerate bone repair. Methods: We have synthesized mesoporous silica-coated magnetic nanoparticles doped with cobalt ions (Co-MMSNs) and assessed their capacity to quicken bone regrowth in a mouse model of DO. Furthermore, local injection of the Co-MMSNs significantly accelerated bone healing in DO, as demonstrated by X-ray imaging, micro-CT, mechanical tests, histological evaluation, and immunochemical analysis. Results: In vitro, the Co-MMSNs exhibited good biocompatibility and induced angiogenic gene expression and osteogenic development in bone mesenchymal stem cells. And the Co-MMSNs can promote bone regeneration in a rat DO model. Discussion: This study demonstrated the significant potential of Co-MMSNs to shorten the DO treatment duration and effectively reduce the incidence of complications.

Total flavonoids of Rhizoma Drynariae enhances CD31hiEmcnhi vessel formation and subsequent bone regeneration in rat models of distraction osteogenesis by activating PDGF­BB/VEGF/RUNX2/OSX signaling axis.

Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney­tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co­immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow­derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet­derived growth factor (PDGF)­BB, VEGF, runt­related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription­quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF­BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF­BB. The protein and mRNA levels of PDGF­BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF­BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic­osteogenic coupling to regenerate bone defects during DO via the PDGF­BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.

Total flavonoids of Rhizoma drynariae ameliorate steroid­induced avascular necrosis of the femoral head via the PI3K/AKT pathway.

Steroid­induced avascular necrosis of the femoral head (SANFH) is a common orthopaedic disease that is difficult to treat. The present study investigated the effects of total flavonoids of Rhizoma drynariae (TFRD) on SANFH and explored its underlying mechanisms. The SANFH rat model was induced by intramuscular injection of lipopolysaccharides and methylprednisolone. Osteoblasts were isolated from the calvariae of neonatal rats and then cultured with dexamethasone (Dex). TFRD was used in vitro and in vivo, respectively. Haematoxylin and eosin staining was used to assess the pathological changes in the femoral head. Terminal deoxynucleotidyl transferase­mediated deoxyuridine triphosphate nick end labelling assay and flow cytometry were conducted to detect apoptosis of osteoblasts. The 2',7'­dichlorofluorescein­diacetate staining method was used to detect reactive oxygen species (ROS) levels in osteoblasts and the 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was used to detect osteoblast proliferation. The expression of caspase­3, Bax, Bcl­2, VEGF, runt­related transcription factor 2 (RUNX2), osteoprotegerin (OPG), osteocalcin (OCN), receptor activator of nuclear factor κB ligand (RANKL) and phosphoinositide 3­kinase (PI3K)/AKT pathway related­proteins were detected via western blotting. It was found that TFRD reduced the pathological changes, inhibited apoptosis, increased the expression of VEGF, RUNX2, OPG and OCN, decreased RANKL expression and activated the PI3K/AKT pathway in SANFH rats. TFRD promoted proliferation, inhibited apoptosis and reduced ROS levels by activating the PI3K/AKT pathway in osteoblasts. In conclusion, TFRD protected against SANFH in a rat model. In addition, TFRD protected osteoblasts from Dex­induced damage through the PI3K/AKT pathway. The findings of the present study may contribute to find an effective treatment for the management of SANFH.

Unprecedented tibial bone lengthening of 33.5 cm by distraction osteogenesis for the reconstruction of a subtotal tibial bone defect. A case report and literature review.

BACKGROUND: We present a case of an immense unprecedented tibial bone lengthening of 33.5 cm. The management of chronic osteomyelitis of the right tibia with subtotal tibial bone defect, talus defect and equinus ankle deformity. We demonstrate limb reconstruction by distraction osteogenesis and correction of ankle deformity with the Ilizarov technique. Limb salvage was preferred as an alternative to amputation to restore basic limb function. CASE PRESENTATION: A 16-year-old male patient fell and injured his right lower leg. He attempted to treat the symptoms with traditional home remedies. During 15 months of self-treating, he developed osteomyelitis of the right tibia and had lost function in his foot. Radiology revealed immense bone defect of the right tibia, including talus bone defect and equinus deformity of the calcaneus. The patient's right tibia was non weight-bearing, had drainage sinus just below his knee and a large scar anteriorly along the entire length of the tibia. CONCLUSION: Upon completion of treatment, the patient was able to avoid amputation of his leg with partially restored function for weight-bearing. He carried himself without assistance after 3 years of lost function in his right leg. Tibial bone distraction osteogenesis of 33.5 cm was done after 90% of the tibial length was defected. To the best of our best knowledge, this case is one of a kind to achieve distraction of tibial bone to such length.

Orthodontic and Surgical Principles for Distraction Osteogenesis in Children with Pierre-Robin Sequence.

Patients with Pierre-Robin sequence recalcitrant to nonsurgical intervention have historically required tracheostomy. Mandibular distraction provides a predictable alternative to tracheostomy. Orthodontic perioperative interventions should be considered, including overcorrection, placement of temporary anchorage devices, elastics, and molding the regenerate. Mandibular distraction can be technically difficult and may cause complications. Performed correctly, mandibular distraction provides patients with a better quality of life than tracheostomy.

Rigid External Distraction with Intranasal Bone-borne Traction Hooks for Midfacial Hypoplasia.

Rigid external distraction is currently performed to correct cases of severe maxillary hypoplasia. As an improvement of this technique, we propose the use of an intranasal bone-borne traction hook. This study is a retrospective chart review of the intranasal bone-borne traction hooks used in the treatment of severe maxillary hypoplasia. There were 110 patients treated with the hooks from 2005 to 2017. The maximum traction force was 7.75 kg, and there were few complications encountered during distraction. There were 76 patients who had the hooks removed under local anaesthesia. A cephalometric analysis was conducted in 56 patients. The average advancement of A-point was 9.9 ± 4.2 mm, 8.4 ± 2.5 mm, 11.0 ± 3.7 mm, 17.9 ± 4.4 mm for the trans-sutural distraction osteogenesis (DO), maxillary anterior segment DO, Le Fort I osteotomy DO and Le Fort III/II osteotomy DO, respectively. The average changes of sella-nasion-point A (SNA) were 8.89 ± 4.30 degrees, 8.21 ± 3.17 degrees, 10.49 ± 3.26 degrees, and 15.10 ± 4.00 degrees, respectively. The A point-nasion-B point (ANB) also showed increases in all procedures with P < 0.001. In conclusion, this technique sufficiently advances the midface and ensures the scars are concealed in the nasal base. The traction hook can bear a large traction force, causes minimal complications and is easily removed.

Investigation of effects of low level laser therapy in distraction osteogenesis.

PURPOSE: The purpose of the study was to investigate the histopathological effects of low level laser therapy (LLLT) application in distraction osteogenesis (DO). MATERIALS AND METHODS: Twenty adult female New Zealand white rabbits were included in the study. Under general anesthesia unilateral mandibular corpus osteotomy was performed. Custom made external distractors were placed to right mandibles of rabbits. After five days of latency period, distractors were activated once a day for 5 days with 1mm/day frequency. Animals in the study group were exposed to LLLT from six different points transcutanously after each distractor activation. Control group was not exposed to laser irradiation. Animals were sacrificed after 15 and 30 days of consolidation periods and mandibles were processed for histopathological investigation under light microscope. Bone healing was analyzed with a semi-quantitative 4 point scale. RESULTS: Osteoblastic activity and vascularization were found higher in the study group than control group after 15 days consolidation. Chondroblastic activity of the control group was significantly higher than the study group in both 15 and 30 days of consolidation groups. Osteoblastic activity and trabecular bone formation were found significantly higher in the study group than the control group after 15 days consolidation. CONCLUSIONS: The use of LLLT in activation period of distraction osteogenesis stimulates bone repair in the early stages of distraction osteogenesis by inducing intramembranous healing and less cartilage tissue formation in the bone callus.

Effect of Laser Bio-Stimulation on Mandibular Distraction Osteogenesis: An Experimental Study.

PURPOSE: The aim of this study was to evaluate the osseous response to laser bio-stimulation clinically and histologically during distraction osteogenesis (DO) induced in the mandibles of mongrel dogs. MATERIALS AND METHODS: Thirty dogs were divided into 3 groups of 10 (5 with and 5 without laser treatment) according to sacrifice periods (2, 4, and 8 weeks after distraction). DO was performed between the mandibular second and third premolars using an internal linear distractor. After a 7-day latency period, the distractor was activated at the rate of 1 mm per day for 10 days followed by a consolidation period during which the right mandibular side was irradiated with a diode laser (wavelength [λ], 970 nm; power, 2 W; spot size, 320 µm; total energy [E], 840 J), whereas the control group was not irradiated, after distraction. Histologic specimens were prepared and histomorphometric analysis of specimens was performed. RESULTS: Clinical examinations showed that the low-intensity laser diode had a pronounced effect on the quality and quantity of newly formed bone in the DO regenerate in the laser groups compared with the control groups. Histopathologic sections from laser groups I, II, and III displayed the bio-stimulatory effect of laser on new bone through an increased rate of osteoblast proliferation and differentiation, an accelerated rate of intramembranous ossification, and increased neoangiogenesis compared with the control groups. Moreover, the histomorphometric results showed that mean bone trabecular size, bone trabecular total area, and bony area fraction of the regenerate were larger and statistically significant (P < .05) especially in laser groups I and II (early stages of bone formation) compared with the control groups. CONCLUSION: The low-level diode laser had a positive role as a potential bio-stimulator and local inducer in enhancing bone formation during DO and resulted in early stability of the bone regenerate, a shorter total treatment time, and improved new bone quality and quantity.

Management of Osteomyelitis-Induced Massive Tibial Bone Defect by Monolateral External Fixator Combined with Antibiotics-Impregnated Calcium Sulphate: A Retrospective Study.

AIM: The present study is aimed at evaluating the effect of combined treatment on massive bone defect using radical debridement, antibiotic calcium sulphate, and monolateral external fixator. METHODS: 35 patients with tibial osteomyelitis received radical debridement, and during surgery antibiotics-impregnated calcium sulphate was used for filling the bone defect. Monolateral external fixator was used to manage the bone defect of average 95 (61-185) cm. RESULTS: Bone union was achieved in 34 patients (97.1%) with no reinfection. One case was presented with reinfection and further debridement was conducted. The average time for the utility of external fixation was 17 (7-32) months, and external fixation index (EFI) was 1.79 mon/cm. The mean follow-up duration after surgery was 33.7 (21-41) months. 19, 13, and 3 patients got excellent, good, and fair bone results, respectively. Meanwhile, functional results were excellent, good, fair, and poor in 13, 15, 6, and 1 patient. The most common complication was pain (100%) and superficial pin-tract infection (22.8%). Delayed maturation was incurred in 2 patients. CONCLUSION: Our study reveals that radical debridement combined with antibiotics-impregnated calcium sulphate can suppress infection, and distraction osteogenesis using monolateral external fixators plays an effective role in managing osteomyelitis-induced massive tibial bone defect.

Sclerostin antibody enhances bone formation in a rat model of distraction osteogenesis.

Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl-Ab) treatment on regenerate volume, density, and strength in a rat model of distraction osteogenesis. Surgical osteotomy was performed on 179 Sprague Dawley rats. After 1 week, rats underwent distraction for 2 weeks, followed by 6 weeks for consolidation. Two treatment groups received biweekly subcutaneous Scl-AbIII (a rodent form of Scl-Ab; 25 mg/kg), either from the start of distraction onward or restricted to the consolidation phase. These groups were compared to controls receiving saline. Measurement modalities included longitudinal DXA, ex vivo QCT, and microCT, tissue histology, and biomechanical four-point bending tests. Bone volume was increased in both Scl-Ab treatments regimens by the end of consolidation (+26-38%, p < 0.05), as assessed by microCT. This was associated with increased mineral apposition. Importantly, Scl-Ab led to increased strength in united bones, and this reached statistical significance in animals receiving Scl-Ab during consolidation only (+177%, p < 0.01, maximum load to failure). These data demonstrate that Scl-Ab treatment increases bone formation, leading to regenerates with higher bone volume and improved strength. Our data also suggest that the optimal effects of Scl-Ab treatment are achieved in the latter stages of distraction osteogenesis. These findings support further investigation into the potential clinical application of sclerostin antibody to augment bone distraction, such as limb lengthening, particularly in the prevention of refracture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1106-1113, 2018.

Effect of strontium citrate on bone consolidation during mandibular distraction osteogenesis.

OBJECTIVES/HYPOTHESIS: Mandibular distraction osteogenesis (MDO) involves a lengthy consolidation phase where complications can occur. Strontium is an element that has been shown to improve bone healing. The objective of this study was to determine whether strontium citrate can be used to enhance bone healing during MDO in a rabbit model. STUDY DESIGN: Prospective animal model study. METHODS: Custom-made MDO devices were placed on 20 New Zealand White rabbits. After a 7-day latency period, distraction was performed at 1 mm/day for 5 days. The study group rabbits (n = 10) received oral strontium citrate; the other 10 rabbits served as controls. Mandibles were removed at the end of the consolidation period (4 weeks). Formation and healing of new bone were evaluated with microcomputed tomography, histology, and a three-point bending mechanical test. RESULTS: New bone formed in all animals, but the consolidation process was enhanced in rabbits that received strontium. The histological analysis showed that study group rabbits had more mature bone. Microcomputed tomographic images demonstrated significantly higher bone density for study group animals, and the three-point bending test results demonstrated that the maximum load of the study group specimens was significantly greater than that of the control group mandibles. CONCLUSIONS: Strontium citrate improved the formation of new bone in the current rabbit model of MDO. The prolonged consolidation period may be shortened with strontium citrate, which may also have the potential to reduce complications. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E212-E218, 2017.

Effect of SDF-1/Cxcr4 Signaling Antagonist AMD3100 on Bone Mineralization in Distraction Osteogenesis.

Distraction osteogenesis (DO) is a widely applied technique in orthopedics surgery, which involves rapid stem cell migration, homing, and differentiation. Interactions between the chemokine receptor Cxcr4 and its ligand, stromal derived factor-1 (SDF-1), regulate hematopoietic stem cell trafficking to the ischemic area and induce their subsequent differentiation. Here, we examined SDF-1 expression and further investigated the role of SDF-1/Cxcr4 signaling antagonist AMD3100 during bone regeneration in rat DO model. The results showed that expression levels of SDF-1 and osteogenic genes were higher in DO zones than in the fracture zones, and SDF-1 expression level was the highest at the termination of the distraction phase. Radiological, mechanical, and histological analyses demonstrated that the local administration of AMD3100 (400 µM) to DO rats significantly inhibited new bone formation. In the rat bone marrow mesenchymal stem cells culture, comparing to the group treated with osteogenic induction medium, AMD3100 supplement led to a considerable decrease in the expression of alkaline phosphatase and early osteogenic marker genes. However, the amount of calcium deposits in rat MSCs did not differ between the groups. Therefore, our study demonstrated that the DO process induced higher expression of SDF-1, which collated to rapid induction of callus formation. Local application of SDF-1/Cxcr4 signaling antagonist AMD3100 significantly inhibited bone mineralization and osteogenesis in DO, which may represent a potential therapeutic approach to the enhancement of bone consolidation in patients undergoing DO.

Staphylococcal enterotoxin C2 expedites bone consolidation in distraction osteogenesis.

Distraction osteogenesis (DO) technique could be used to manage large-size bone defect successfully, but DO process usually requires long duration of bone consolidation. Innovative approaches for augmenting bone consolidation are of great need. Staphylococcal enterotoxin C2 (SEC2) has been found to suppress osteoclastogenesis of mesenchymal stem cells in vitro. In this study, we investigated the effect of SEC2 on proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). Further, we locally administrated SEC2 (10 ng/ml) or PBS into the distraction gap in Sprague-Dawley male rat DO model every 3 days till termination at 3 and 6 weeks. The regenerates were subjected to X-rays, micro-computed tomography, mechanical testing, histology, and immunohischemistry examinations to assess new bone quality. SEC2 had no effect on cell viability. The calcium deposition was remarkably increased and osteogenic marker genes were significantly up-regulated in rBMSCs treated with SEC2. In rat DO model, SEC2 group had higher bone volume/total tissue volume in the regenerates. At 6 weeks, mechanical properties were significantly higher in SEC2-treated tibiae comparing to the control group. Histological analysis confirmed that the new bone had improved quality in SEC2 treated group, where the osteocalcin and osterix expression in the regenerates was up-regulated, indicating faster bone formation. The current study demonstrated that SEC2 local injection promotes osteogenesis and enhanced bone consolidation in DO. The findings support application of SEC2 as a potential novel strategy to expedite bone consolidation in patients undergoing DO treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1215-1225, 2017.

Influence of a Magnetic Field and Laser Therapy on the Quality of Mandibular Bone During Distraction Osteogenesis in Rabbits.

PURPOSE: This study evaluated the use of low-level laser therapy (LLLT) and exposure to a magnetic field (MF) during distraction osteogenesis. MATERIALS AND METHODS: The sample consisted of 18 rabbits divided into 3 groups of 6 animals each: control, MF exposure (briefly, magnetized gold-coated washers were placed next to the distractor device), and LLLT exposure (830 nm applied every 48 hours over 4 points [dose, 5 J/cm2] during the consolidation period). The same distraction osteogenesis protocol was used in all 3 groups (0.5 mm every 12 hours for 1 week). RESULTS: Quantitative microscopic analysis of sections stained with hematoxylin and eosin showed a statistically significant difference in the amount of newly formed bone in the MF group compared with the LLLT group (P = .006). The number of cells with more than 3 argyrophilic nucleolar organizer regions also was significantly different between the LLLT and control groups (P = .038). CONCLUSION: Distraction osteogenesis effectively promoted bone lengthening. The LLLT group exhibited a larger amount of newly formed bone and a larger number of osteoblasts in the cell division phase, but the difference was not statistically relevant compared with the control group.

Knee Joint Distraction Compared to Total Knee Arthroplasty for Treatment of End Stage Osteoarthritis: Simulating Long-Term Outcomes and Cost-Effectiveness.

OBJECTIVE: In end-stage knee osteoarthritis the treatment of choice is total knee arthroplasty (TKA). An alternative treatment is knee joint distraction (KJD), suggested to postpone TKA. Several studies reported significant and prolonged clinical improvement of KJD. To make an appropriate decision regarding the position of this treatment, a cost-effectiveness and cost-utility analysis from healthcare perspective for different age and gender categories was performed. METHODS: A treatment strategy starting with TKA and a strategy starting with KJD for patients of different age and gender was simulated. To extrapolate outcomes to long-term health and economic outcomes a Markov (Health state) model was used. The number of surgeries, QALYs, and treatment costs per strategy were calculated. Costs-effectiveness is expressed using the cost-effectiveness plane and cost-effectiveness acceptability curves. RESULTS: Starting with KJD the number of knee replacing procedures could be reduced, most clearly in the younger age categories; especially revision surgery. This resulted in the KJD strategy being dominant (more effective with cost-savings) in about 80% of simulations (with only inferiority in about 1%) in these age categories when compared to TKA. At a willingness to pay of 20.000 Euro per QALY gained, the probability of starting with KJD to be cost-effective compared to starting with a TKA was already found to be over 75% for all age categories and over 90-95% for the younger age categories. CONCLUSION: A treatment strategy starting with knee joint distraction for knee osteoarthritis has a large potential for being a cost-effective intervention, especially for the relatively young patient.

The Radiological and Stereological Analysis of the Effect of Low-Level Laser Therapy on the Mandibular Midline Distraction Osteogenesis.

OBJECTIVE: The aim of this study was to evaluate the effect of low level laser therapy (LLLT) on bone mineral density by using high-resolution computerized tomography (HR-CT) and stereology in patients subjected to mandibular midline distraction. METHODS: Nine patients between the ages of 13 and 16 years with mandibular transverse deficiency (>5 mm) were evaluated. Mandibular midline distraction osteogenesis was performed for all the patients. The patients were divided into 2 groups: the control group (n = 4) and the laser group (n = 5). GaAlAs, 830 nm wavelength, power of 40 mW, energy of 8.4 J/cm2 dose per spot, was directly applied from 2 points on the mandibular midline. The laser was applied in 8 treatment sessions at 48-hour intervals. Bone mineral density and volume of the newly formed bone were analyzed using HR-CT and stereological methods. RESULTS: A higher bone mineral density rate was found in the laser group (P < 0.05). A higher newly formed immature bone rate was found in the control group (P < 0.001). These findings suggest that more mature bone may also have a greater mineral organization than that of immature newly formed bone, which is shown by HR-CT and stereological results. CONCLUSIONS: The retention period can be shortened and mineralization may be increased by using LLLT in mandibular distraction osteogenesis.

Changes over time in callus formation caused by intermittently administering PTH in rabbit distraction osteogenesis models.

BACKGROUND: Changes over time in the callus during intermittent administration of parathyroid hormone (PTH) were studied in rabbit distraction osteogenesis models. METHOD: Models of distraction osteogenesis in Japanese white rabbits were created, and distraction osteogenesis (total length: 10.5 mm) was performed for 2 weeks. Simultaneously with the start of distraction, 30 rabbits received 4 weeks of subcutaneous administration of 30 µg/kg of PTH(1-34), teriparatide, (P-group: n = 15) or saline (N-group: n = 15) every other day. The tibias of five rabbits were dissected at 6, 8, and 10 weeks after surgery to perform bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), and mechanical testing. RESULTS: The mean BMD had no significant differences over time at 6, 8, and 10 weeks after surgery between the P-group and the N-group. On pQCT, the P-group had significant increases in total bone cross-sectional area of the callus compared to the N-group at 8 and 10 weeks after surgery. On mechanical testing, the P-group's absorption energy had not changed at 6 weeks after surgery compared to the N-group, but it had significantly increased at 8 weeks. At 10 weeks after surgery, the N-group's absorption energy rapidly increased, and the difference between the two groups disappeared. CONCLUSION: The intermittent administration of PTH(1-34), teriparatide, for 4 weeks every other day from the start of distraction had the potential to shorten the callus maturation period in the rabbit distraction osteogenesis models.

Evaluation of the effect of low-level diode laser therapy applied during the bone consolidation period following mandibular distraction osteogenesis in the human.

The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) on new bone formation obtained by distraction osteogenesis in the early consolidation period. Ten selected patients with bilateral mandibular retrusion seen at the Nasser Institute Hospital, Egypt between June 2009 and June 2012 underwent this clinical trial; seven were female and three were male, and their mean age was 31±5.1 years. The left mandible of each patient was assigned to group A (n=10) and the right mandible to group B (n=10); mandibular distraction osteogenesis was performed on both sides and then LLLT was used in group B only. The amounts of bone acquired were compared according to their radiographic density on digital panoramic radiographs after 6, 12, 24, and 54 days of consolidation. Statistically significant differences in bone density were found between the two groups. Group B showed bone consolidation and growth differences on day 6 (P=0.402), day 12 (P=0.006), day 24 (P=0.021), and day 54 (P=0.028). The use of LLLT on distracted bone was found to increase the quality and quantity of bone and to shorten the consolidation period, allowing early removal of the distractor and resulting in decreased morbidity and relapse.