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The role of melatonin as a link between head injury and enhanced osteogenesis.

We hypothesize that in the case of an individual with a head injury, melatonin can enhance osteogenesis. In virtually all species to date whether nocturnal or diurnal, melatonin is synthesized and secreted during the dark phase of the day. In traumatic subarachnoid hemorrhages, in the hypothalamic syndrome, the melatonin content was very high in liquor. This was determined by a fluorimetric method, especially modified for this purpose. Osteoblastic activity rises with the increase of melatonin. Healing of a fracture of long or large bone can often be accelerated in patients with severe traumatic brain injury. However, a melatonin which could perhaps induce enhanced osteogenesis has not yet been identified. Melatonin might cause early bone healing and hypertrophic callus.

Animals↗

Mechanobiology of mandibular distraction osteogenesis: finite element analyses with a rat model.

Three-dimensional finite element (FE) analyses were performed to characterize the local mechanical environment created within the tissue regenerate during mandibular distraction osteogenesis (DO) in a rat model. Finite element models were created from three-dimensional computed tomography image data of rat hemi-mandibles at four different time points during an optimal distraction osteogenesis protocol (i.e., most successful protocol for bone formation): end latency (post-operative day (POD) 5), distraction day 2 (POD 7), distraction day 5 (POD 10), and distraction day 8 (POD 13). A 0.25 mm distraction was simulated and the resulting hydrostatic stresses and maximum principal tensile strains were determined within the tissue regenerate. When compared to previous histological findings, finite element analyses showed that tensile strains up to 13% corresponded to regions of new bone formation and regions of periosteal hydrostatic pressure with magnitudes less than 17 kPa corresponded to locations of cartilage formation. Tensile strains within the center of the gap were much higher, leading us to conclude that tissue damage would occur there if the tissue was not compliant enough to withstand such high strains, and that this damage would trigger formation of new mesenchymal tissue. These data were consistent with histological evidence showing mesenchymal tissue present in the center of the gap throughout distraction. Finite element analyses performed at different time points during distraction were instrumental in determining the changes in hydrostatic stress and tensile strain fields throughout distraction, providing a mechanical environment rationale for the different levels of bone formation in end latency, and distraction day 2, 5, and 8 specimens.

Animals↗

A multidisciplinary approach to restoring an acquired palatal defect using distraction osteogenesis: a clinical report.

Prosthetic and surgical procedures can be applied to rehabilitate acquired palatal defects. Distraction osteogenesis may be used to narrow the defect to facilitate bone and soft tissue closure. This clinical report describes a multidisciplinary approach to the closure of a palatal defect with distraction osteogenesis, comprehensive orthodontic treatment, surgical soft tissue flap reconstruction of the residual soft tissue defect, implant placement in the newly created edentulous ridge, and restoration with an implant-supported prosthesis.

Adult↗

Analysis of complications following alveolar distraction osteogenesis and implant placement in the partially edentulous mandible.

OBJECTIVE: The purpose of this retrospective study was to evaluate complications before, during, and after vertical alveolar distraction osteogenesis and to assess the survival rate of dental implants placed in distracted bone. STUDY DESIGN: In a consecutive series, 37 patients with 45 alveolar ridge deficiencies of the partially edentulous mandible were treated with 14 intraosseous and 31 subperiosteal distraction devices. Seventy-two dental implants could be placed at the time of distractor removal and 21 implants at a second stage. RESULTS: Complications associated with the distraction procedure affected 75.7% of patients. The majority of complications were of minor nature with the exception of fractures of basal bone (n = 3), fracture of transport segment (n = 1), breakage of distractor (n = 1), and severe mechanical problems (n = 3). Eleven secondary grafting procedures were necessary to allow the placement of dental implants. Implant survival was 95.7% (mean postloading follow-up: 35.7 months). CONCLUSION: Vertical alveolar distraction osteogenesis is not an uncomplicated procedure; however, long-term survival of dental implants inserted into distracted areas is satisfactory.

Adolescent↗

Alveolar distraction osteogenesis of bone graft reconstructed mandible.

This case report describes a patient who had severe mandibular bony deficiency as a result of excision of aggressive central giant cell granuloma. The defect was reconstructed with iliac bone graft. Four years later vertical distraction osteogenesis was performed on the grafted mandible in order to obtain a satisfactory bony height of mandibular ridge. Distraction osteogenesis can be a good alternative for the reconstruction of mandibular deficiencies.

Alveolar Ridge Augmentation↗

Bite force and occlusal contact area changes following mandibular widening using distraction osteogenesis.

OBJECTIVE: To examine changes in bite force and occlusal contact area after mandibular widening by distraction osteogenesis using pressure-sensitive sheet (Dental-Prescale; Fuji Photo Film, Tokyo, Japan). STUDY DESIGN: Fifteen patients with transverse mandibular deficiency (6 to 9 mm, mean distraction interval: 8 mm) were examined. They were measured just before the operation and at 1 week, 1 month, 3 months, 6 months, and 1 year after the operation. Ten control subjects with normal occlusion were also measured. RESULTS: Both bite force and occlusal contact area were lowest at 1 month postoperatively. The values of bite force and occlusal contact area steadily increased thereafter. The bite force and occlusal contact area reached to the preoperative levels at 6 months after operation and slightly above the preoperative level at 12 months after operation. There were no statistically significant differences between 12 months and the control values for bite force measurements (P > .05). CONCLUSION: Although statistically not significant, this study suggests that mandibular symphyseal distraction osteogenesis increases the bite force and occlusal contact area in patients with transverse mandibular deficiency.

Adolescent↗

Vertical distraction osteogenesis of fibula transplant for mandibular reconstruction: a case report.

Bone continuity defects in the mandible are caused by tumor surgery, trauma, infection, or osteoradionecrosis. Today, reconstruction of long-span mandibular defects with a free fibular flap is a routine procedure. However the bone height of the mandible after reconstruction is about half that of the dentulous mandible. Therefore, the deficiency in bone height makes implant placement impractical. In our case, because it was necessary to restore the mandibular height, a vertical distraction osteogenesis was performed on the grafted mandible of the patient who was referred to our clinic with a reconstructed mandible owing to a gunshot injury. As a result, the vertical discrepancy between the fibula and the native hemimandible of the patient was corrected. And the placement of dental implants was performed without any complications. In conclusion, we believe that the vertical distraction osteogenesis of free vascularized fibula flaps is a reliable technique that optimizes implant positioning for ideal prosthetic rehabilitation.

Adult↗

Osteogenesis imperfecta.

Osteogenesis imperfecta is a relatively common hereditary connective tissue disorder characterized by bone fragility and fractures. Other frequently affected tissues include tendons, ligaments, skin, sclera, teeth, and middle and inner ear. Molecular studies have demonstrated that most cases result from mutations affecting the genes responsible for the formation of type 1 collagen. The phenotypic presentation varies from mild to lethal. Commonly observed dental abnormalities include dentinogenesis imperfecta and malocclusion. Medical therapies using bisphosphonates have resulted in reduced fracture risk and decreased bone pain. To date, no cases of bisphosphonate-associated osteonecrosis have been reported. With appropriate precautions, the patient with osteogenesis imperfecta can tolerate and benefit from the delivery of necessary dental care to control oral disease, improve function, and improve esthetics.

Bone Density Conservation Agents↗

The role of TGF-beta signaling in regulating chondrogenesis and osteogenesis during mandibular development.

During craniofacial development, Meckel's cartilage and the mandible bone derive from the first branchial arch, and their development depends upon the contribution of cranial neural crest (CNC) cells. We previously demonstrated that conditional inactivation of Tgfbr2 in the neural crest of mice (Tgfbr2(fl/fl);Wnt1-Cre) results in severe defects in mandibular development, although the specific cellular and molecular mechanisms by which TGF-beta signaling regulates the fate of CNC cells during mandibular development remain unknown. We show here that loss of Tgfbr2 does not affect the migration of CNC cells during mandibular development. TGF-beta signaling is specifically required for cell proliferation in Meckel's cartilage and the mandibular anlagen and for the formation of the coronoid, condyle and angular processes. TGF-beta-mediated connective tissue growth factor (CTGF) signaling is critical for CNC cell proliferation. Exogenous CTGF rescues the cell proliferation defect in Meckel's cartilage of Tgfbr2(fl/fl);Wnt1-Cre mutants, demonstrating the biological significance of this signaling cascade in chondrogenesis during mandibular development. Furthermore, TGF-beta signaling controls Msx1 expression to regulate mandibular osteogenesis as Msx1 expression is significantly reduced in Tgfbr2(fl/fl);Wnt1-Cre mutants. Collectively, our data suggest that there are differential signal cascades in response to TGF-beta to control chondrogenesis and osteogenesis during mandibular development.

Animals↗

Effect of pamidronate on distraction osteogenesis and fixator-related osteoporosis.

We examined the effect on bone mineral density (BMD), bone mineral content (BMC) and mechanical properties of a single 1.0 mg/kg dose of the bisphosphonate pamidronate (Novartis), in a distraction osteogenesis model in immature rabbits. Twenty rabbits underwent a tibial osteotomy. Ten rabbits received pamidronate 1.0 mg/kg via ear vein intra-operatively while 10 received saline infusions only. After a 24 h latency, all underwent distraction of 0.375 mm twice daily for 15 days. The animals were culled at 42 days. After culling, the distracted and non-distracted tibiae were examined by quantitative computer tomography (QCT). The volumetric bone mineral density (vBMD, mg/cm(3)) in the bone proximal and distal to the regenerate in the operated limb was increased by a mean of 11 and 14%, respectively, compared to controls (P<0.05). The vBMD of the regenerate bone was increased by a mean of 8% over controls (NS, P=0.17). The bone mineral content (BMC, mg) was increased by 23% (proximal and distal) (P<0.05) in the bone surrounding the lengthening and there was a 17% trend towards an increase in the regenerate (NS, P=0.3). Four-point bending analysis documented that the load to failure was increased by 32% from 436 to 574 N (P<0.01) in the pamidronate group. The modulus of elasticity was not different between the control and pamidronate groups (P=0.3), and in both groups was only approximately one-third of the intact tibiae (P<0.001). The administration of a single dose of pamidronate can improve the bone mineral density, content and mechanical properties of a bone undergoing distraction osteogenesis.

Animals↗

Effect of long-term calcitonin therapy by injection and nasal spray on the incidence of fractures in osteogenesis imperfecta.

The effect of calcitonin therapy by injection or nasal spray on the incidence of bone fractures was studied in patients with osteogenesis imperfecta. In contrast to injection of calcitonin, intranasal administration of calcitonin twice a week for 2 weeks, followed by 2 weeks of no therapy, was simple and seemed beneficial for decreasing bone fractures in patients with osteogenesis imperfecta.

Administration, Intranasal↗

Therapy of osteogenesis imperfecta with synthetic salmon calcitonin.

We evaluated the long-term use of synthetic salmon calcitonin in the management of osteogenesis imperfecta tarda and congenita. Forty-eight children, ranging in age from 6 months to 15 years, and two young adults, received synthetic salmon calcitonin 2 MRC units/kg three days a week and a daily oral calcium supplement of 230 to 345 mg. The annual fracture rate was decreased during calcitonin therapy as compared to the period preceding therapy. There was an increase in the ability of the patient to stand and move and in the subjective feeling of strength in the lower extremities during calcitonin therapy. There was also a significant improvement in radiographic bone density, as determined by the method of photodensitometry, in patients under 5 years of age. Long-term administration of synthetic salmon calcitonin may be beneficial to young children with osteogenesis imperfecta.

Adolescent↗

Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta.

We report two infants with bone deformities and multiple fractures reminiscent of osteogenesis imperfecta, but also having ocular proptosis with orbital craniosynostosis, hydrocephalus, and distinctive facial features. Both infants were normal at birth, but multiple compression fractures of the long bones were noted shortly thereafter, followed by extensive demineralization and culminating in recurrent diaphyseal fractures of the weight-bearing bones before the first birthday. The striking similarity of both the distinctive dysmorphic features and the unique pattern of fractures in two unrelated individuals suggests that this is a previously unrecognized form of osteogenesis imperfecta. Despite the craniosynostosis and hydrocephalus, intellectual performance is unimpaired in both individuals. Bone biopsy in one patient revealed decreased bone volume and increased bone resorption without compensatory new bone formation. Extensive laboratory investigations have not identified a cause, nor have they clarified pathogenesis; further elucidation will require the identification and study of new cases.

Craniosynostoses↗

Sustained expression of transforming growth factor-beta1 by distraction during distraction osteogenesis.

Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. In our previous studies, we have shown that the tension at the distraction gap correlated with the plasma bone specific alkaline phosphatase activity during distraction. Transforming growth factor-beta1 (TGF-beta1) has been shown to have a regulatory role in alkaline phosphatase activity during fracture healing. This study is to investigate the expression of TGF-beta1 during distraction as a biological response to mechanically stimulated osteoblastic activity by immunohistochemistry. The expression of TGF-beta1 in the distraction callus was compared with that in the fracture callus. During the distraction phase, the osteoblasts and osteocytes expressed a high level of TGF-beta1. Moderate expression of TGF-beta1 was observed in fibroblast-like cells in the fibrous zone of the distraction callus. After the distraction stopped, the expression of TGF-beta1 in different cell types decreased. In fracture healing, the strong expression of TGF-beta1 declined after the first week. Our results showed that the mechanical force induced and sustained TGF-beta1 expression in osteoblasts and fibroblasts-like cells of the distraction callus. Transforming growth factor-beta1 may play a role in transducing mechanical stimulation to biological tissue during in distraction osteogenesis.

Animals↗

[Elastic sliding central medullary nailing with osteogenesis imperfecta. Fourteen cases at eight years follow-up].

PURPOSE OF THE STUDY: Elastic sliding centromedullary nailing (ESCN) proposed by Métaizeau in 1987 for the prevention and treatment of limb fractures in osteogenesis imperfecta has never been evaluated. A multicentric serie was studied in order to evaluate results of these procedure. MATERIAL AND METHODS: Thirty-six ESCN procedures were performed in fourteen patients. Percutaneous pinning was used for the femur and distal tibia and arthrotomy for the distal femur as needed and in all cases for the proximal tibia. The pins were bent in compliance with the principles of the ESCN system. The ends of the pins were bent back to form a U pushed into the epiphysis. Reaxing osteotomies required minimal incisions. Age at the first procedure, the number of procedures and complications, and time between procedures were recorded. Pin overlap and the angle formed were also recorded. Pin gliding was evaluated. Ability to walk with or without assistance was noted. RESULTS: The medullary canal measured 4 to 10 mm. The first procedure was performed at a mean age of four years (range 15 days to 10 years). Follow-up was eight years (range 1-12). There were 2.5 procedures per patient (range 1-5). Pins had to be changed in 75% of the bone segments. Mean time between two procedures was 3.2 years. There were no cases of defective sliding or infection. There were four cases of secondary fracture with a mean 30% pin overlap, two pin migrations, one nonunion, and one shortening. The majority of the complications occurred after the age of five years. At last follow-up, three patients could not walk, four walked with aids, and eight without aids. DISCUSSION: The advantages of the technique (size of the pins, nailing without reaming, pin sliding in all cases, low cost) must not overshadow the drawbacks (risk of pin deformation and migration, secondary fracture). Secondary fractures might be limited by discrete valgus of the femoral shaft and preventive pin change when the angle formed approaches 30 degrees and when there is only 30% overlap left. Use of telescopic nails before the age of five years increases the risk of complications while most of the complications observed with ESCN occur after the age of five years. Twenty-five percent of the ESCN complications involved only the femur. The percent of secondary fractures was less than with telescopic nailing (3.6% versus 11%) but there were more cases of nail migration. All pins slid, compared with 6% failure of elongation with telescopic nails. Although proof is not available, surgical treatment of osteogenesis imperfecta before the age of five years appears to provide more rapid functional progress. CONCLUSION: Sliding centromedulary nailing is an attractive alternative before the age of five years. In older children and to the end of growth, telescopic nail or pinning should be discussed although pinning may permit more secondary fractures which can be limited by rigorous surveillance of pin position.

Age Factors↗

Ulnar artery aneurysm in osteogenesis imperfecta.

A case of acute thrombosis of an ulnar artery aneurysm in a patient with osteogenesis imperfecta tarda is described. The pathophysiology of osteogenesis imperfecta is reviewed and the possible association of defective collagen maturation and aneurysm formation is postulated. Most ulnar artery aneurysms or thromboses should be surgically resected and the artery repaired by microsurgical technique with primary anastomosis if possible or a venous interpositional graft if direct repair is not possible without tension.

Adult↗

Distraction osteogenesis in Pierre Robin neonates with airway obstruction.

Mandibular distraction osteogenesis can be a safe and effective way to avoid tracheostomy placement in selected neonates with Pierre Robin sequence,with or without other associated syndromes. In non-syndromic Pierre Robin sequence syndromes, this procedure, in the current author's experience, has provided definitive correction of both airway obstruction and micrognathia. The cost to patients and families appropriately treated by mandibular distraction osteogenesis is substantially less than tracheostomy. Mandibular distraction does not involve the ongoing maintenance, medical care, and high risk of mortality associated with tracheostomy. A support team of pediatric anesthesia, pulmonary, and otolaryngology specialists is required for the safe and successful selection and treatment of this group of patients with Pierre Robin sequence using mandibular distraction. The author's investigation of this group is ongoing.

Airway Obstruction↗