Rat mandibular distraction osteogenesis: Part I. Histologic and radiographic analysis

The application of distraction osteogenesis to craniofacial surgery has altered the approach and treatment of congenital and acquired craniofacial defects. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been described extensively, relatively little is known about the molecular regulation of this process. The elucidation of the molecular mechanisms of distraction osteogenesis has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Molecular analysis of distraction osteogenesis has been hindered by the use of large animal models in which only limited genetic information is available. In this study, a rat model of mandibular distraction osteogenesis is described. This report includes a pilot study (n = 50) to develop an appropriate distraction device and to determine the optimal placement of the osteotomy. The study subsequently included 80 animals, 35 of which were distracted at a rate of 0.25 mm per day for 6 days (1.5 mm total) and 35 that were distracted at a rate of 0.25 mm twice per day (3.0 mm total). These animals were killed at various time points (after latency and during the distraction and consolidation periods) and displayed histologic and radiographic findings of membranous bone distraction osteogenesis that were consistent with those in large ,animal and clinical models. In addition, five animals each were acutely lengthened 1.5 mm and 3.0 mm and demonstrated a fibrous nonunion. Furthermore, the utility of this model is demonstrated in the analysis of the molecular mechanisms of distraction osteogenesis by applying the polymerase chain reaction to total cellular RNA isolated from normal and distracted rat mandibles. In conclusion, it is believed that the rat model of distraction osteogenesis has significant advantages over traditional models, including decreased costs and facilitation of molecular analysis.     

Rat mandibular distraction osteogenesis: II. Molecular analysis of transforming growth factor beta-1 and osteocalcin gene expression

Distraction osteogenesis is a powerful technique capable of generating viable osseous tissue by the gradual separation of osteotomized bone edges. Although the histologic and ultrastructural changes associated with this process have been extensively delineated, the molecular events governing these changes remain essentially unknown. We have devised a rat model of mandibular distraction osteogenesis that facilitates molecular analysis of this process. Such information has significant clinical implications because it may enable targeted therapeutic manipulations designed to accelerate osseous regeneration. In this study, we have evaluated the expression of transforming growth factor beta-1, a major regulator of osteogenesis during endochondral bone formation and development, and osteocalcin, an abundant noncollagenous extracellular matrix protein implicated in the regulation of mineralization and bone turnover. The right hemimandible of 36 adult male rats was osteotomized, and a customized distraction device was applied. Animals were allowed to recover and, after a 3-day latency period, were distracted at a rate of 0.25 mm twice daily for 6 days followed by a 2- or 4-week consolidation period. Distraction regenerate was harvested after the latency period, days 2, 4, or 6 of distraction, and after 2 or 4 weeks of consolidation and processed for Northern analysis (n = 4 at each time point) and immunohistochemical localization of TGF-beta1 (n = 2 at each time point). Six sham-operated animals (i.e., skin incision without osteotomy) were also killed (immediately postoperatively), and the mandibles were harvested and prepared in a similar fashion. Equal loading and transfer of RNA for Northern analysis was ensured by stripping and probing membranes with a probe against GAPDH (a housekeeping gene). Our results demonstrate that the spatial and temporal patterns of TGF-beta1 mRNA expression and protein production coincide with osteoblast migration, differentiation, and extracellular matrix synthesis. In addition, we demonstrate that TGF-beta1 production may be an important regulator of vasculogenesis during mandibular distraction osteogenesis. Finally, we have shown that osteocalcin gene expression coincides temporally with mineralization during rat mandibular distraction osteogenesis.     

Basement membrane of blood vessels during distraction osteogenesis

A canine model of distraction osteogenesis has recently been developed that permitted the evaluation of bone formation and its vascularization during bifocal callotasis. In this model, the authors examined the composition of the blood vessels during distraction osteogenesis of the mandible for laminin and for Type IV collagen, both constituents of the vascular basement membrane. At the fibrous distraction site, at the juncture of the free cortical surface and the regenerated bone, and at the abutting cortical surfaces at the distal margin of the defect, laminin and Type IV collagen were present in all vessels.     

Cloning, characterization, and chromosomal localization of human superillin (SVIL)

The specific aim of this study was to determine the response of alveolar bone after it was augmented vertically using distraction osteogenesis and subsequently loaded with implant restorations. Four dogs each had four implants placed horizontally into an edentulous mandibular quadrant and, after integration, a distraction osteogenesis device was fabricated in the laboratory. An osteotomy was made to allow the crest of the alveolar ridge to be distracted vertically. After 10 mm of vertical distraction, the device was stabilized with light cured resin. Following bone fill confirmation of the distraction gap at 10 weeks, two implants were placed into the ridges, one in distracted bone and one in nondistracted bone. After 4 months for implant integration, freestanding prostheses were fabricated. Crestal bone levels were evaluated throughout the period of function. Animals were sacrificed after 1 year of loading, for histologic evaluation of the bone. The vertical ridge augmentation averaged 8.85 +/- 1.05 mm after 10 weeks of healing following distraction, without change over 1 year of implant loading. Histologic examination showed that bone had formed between the distracted segments, creating an augmented ridge. The average thickness of the labial cortex in the distraction gap was significantly thinner than the lingual cortex in distracted bone and the lingual and labial nondistracted cortical bone. The presence of the dental implant did not significantly affect cortical bone thickness. Serial sections showed that implants remained integrated and functional without soft tissue inflammation. Dental implants placed into alveolar ridges augmented with the technique of distraction osteogenesis maintained bone and were functional for the length of this study.     

Content and predictors of the ethnic identity of Russian-speaking immigrant adolescents in Finland

Even though osteodistraction has been well established in the extremities, the parameters used in craniofacial distraction have been essentially borrowed from orthopaedic experience. Latency is widely practised but its relevance has not been fully investigated. The purpose of this study was to establish the role of latency in mandibular distraction osteogenesis. Twenty-two growing Wethers sheep were allocated to four experimental groups. Six animals were allocated to each of Groups A, B and C and underwent bilateral mandibular corticotomies and attachment of an external lengthening device. Latent periods of 0, 4 and 7 days respectively were observed prior to beginning distraction. The distraction protocol consisted of a rate of 0.5 mm twice daily for 20 days, followed by a consolidation phase of 20 days after which the sheep were killed. Histology, bone densitometry and 3-point mechanical testing were performed on the harvested mandibles. Group D formed the control group (n = 4). Histologically, the distracted bone exhibited bone formation primarily via intramembranous ossification with scattered islands of cartilage. The regenerated bone had mechanical properties significantly weaker than the undistracted control group (P < 0.05), but between the experimental groups no statistically significant differences were demonstrable either in mechanical strength or DEXA density. These data indicate that a change in latency does not alter the properties of the regenerated bone in mandibular distraction osteogenesis and indeed no latent interval may be necessary at all in craniofacial distraction. This has implications for the duration of device fixation in distraction procedures.     

Evaluation of the mechanical environment during distraction osteogenesis

Physical forces have been hypothesized to direct the process of bone regeneration during distraction osteogenesis. However, despite significant clinical experience, relatively little is known about how the mechanics of distraction influence bone formation. This study investigated net fixator forces and strains in the distraction callus during bilateral lengthening of tibiae in New Zealand White rabbits. Distractions yielded a classic viscoelastic response with a sharp increase in fixator force, followed immediately by significant relaxation. Tension acting on mesenchymal gap tissue caused by distraction was estimated to reach more than 30 N by the time full lengthening was achieved. Average maximum cyclic strains within the distraction zone during ambulation were estimated to be 14% to 15% and supported by the results of fluoroscopic imaging. Paradigms for fracture healing have hypothesized that such strains are incompatible with new bone formation. The documented clinical success of distraction osteogenesis at stimulating large volumes of new bone suggests that other mechanisms that warrant additional investigation may be at work during distraction.     

Distraction osteogenesis for lengthening of the hard palate: Part I. A possible new treatment concept for velopharyngeal incompetence. Experimental study in dogs

Many procedures have been described to correct velopharyngeal incompetence. Significant complications can occur, and the results may not be satisfactory. If the short soft palate has satisfactory muscle function and if it could be moved toward the posterior pharyngeal wall by distraction osteogenesis of the hard palate, an entirely new concept of treatment for velopharyngeal incompetence would be available. The object of the present study was to explore the possibility of osteogenesis occurring in the hard palate in dogs after gradual distraction (callus distraction). Six adult, mix-bred dogs were anesthetized, and the palatal mucosa was elevated. A midpalatal transverse osteotomy and two lateral osteotomies were performed. Tantalum bone markers for cephalometric analysis were placed, and an individually fabricated, orthodontic-like distraction device with an expansion screw in the sagittal direction was inserted. The device was stabilized on the premolars and fixed to the palatal bone with titanium miniscrews. Gradual distraction began after a latency period of 10 to 18 days. The rate of the distraction varied from 0.25 to 0.75 mm per day. The device was left in place for 6 to 8 weeks after expansion to allow for bony consolidation. Assessment was by direct examination, cephalograms, computed tomography, and histology with bone labeling. Impressions of the jaws were taken preoperatively and after device removal to examine plaster cast changes in the dental occlusion. Cephalometric and computed tomographic scan analysis demonstrated a distraction of up to 8 mm. All gaps were filled with de novo osteogenesis. Comparison of the plaster casts revealed no change in the occlusion. At 1 month after distraction, the computed tomographic scan showed the first signs of ossification of the experimental gap from the anterior and posterior bone ends. After 4.5 months ossification was almost complete with a small translucent zone in the middle of the experimental gap. After 7 months ossification was complete.     

Internal calvarial bone distraction in rabbits with delayed-onset coronal suture synostosis

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.     

Effects of group discussion and guided patient care experience on nurses'' attitudes towards care of patients with AIDS

An in vivo study was carried out to determine if capacitive coupled electrical stimulation increased the rate of recovery of strength of regenerate bone produced as a result of lengthening by the Ilizarov technique. Thirty-four adult male beagles underwent a right tibial mid-diaphyseal corticotomy, followed by a 5-day delay, and then 21 days of lengthening (1 mm/day). At the start of the post-distraction period (day 27), stimulation (3-6.3 V peak to peak, 5-10 mA root-mean-square at 60 kHz) was applied for 28 days to one group. The nonstimulated group (n = 17) underwent a 28-day period with no stimulation. From each group, four tibiae were prepared for histology; both ends of the remaining bones were embedded in polymethylmethacrylate and tested in torsion (internal rotation at 4.7 degrees/sec) until failure. Statistically significant changes included a 37% lower maximum torque capacity and a 40% decrease in strain energy to failure in the stimulated group compared with the nonstimulated group. The findings are supported by measured trends to a lower modulus of rigidity (37% decrease) and a smaller percentage of active osteoid perimeter (20% decrease) for the stimulated group. The experimental data suggest that when this dose of capacitive coupled electrical stimulation is applied to the regenerating bone created during distraction osteogenesis, it delays the recovery of bone strength compared with an untreated control.     

Distraction osteogenesis for lengthening of the hard palate: Part II. Histological study of the hard and soft palate after distraction

To correct velopharyngeal incompetence, a new treatment concept was proposed in Distraction Osteogenesis for Lengthening of the Hard Palate: Part I (using lengthening of the hard and soft palate by distraction osteogenesis). Cephalometry and computed tomography showed successful elongation of the posterior hard palate with gradual calcification. Here the sequential use of fluorochrome markers (oxytetracycline, xylenol orange, DCAF [2,4-bis-N-N'-dicarboxymethyl aminomethyl fluorescein], and alizarin complexone) during the distraction and retention period is reported together with the histologic investigations using light and laser scan microscopy without prior demineralization. The experimental gap showed de novo osteogenesis in all dogs. The new bone was always in continuity with the original anterior and posterior palatal bone margins. It either bridged the experimental gap fully or left a small central zone of fibrous tissue, in which eventual ossification occurred. Several distinct zones could be distinguished: A small central zone was found with parallel strains of collagen fibers, oriented longitudinally in the direction of the distraction. Next to this zone a layer of undifferentiated mesenchymal precursor cells was seen in direct contact to newly formed bone. The next zone was coarse woven bone, showing a transition to mature lamellar bone through remodeling. No evidence of endochondral bone formation was found, i.e., all dogs showed exclusively intramembranous bone formation. The soft tissues showed no signs of alteration: in particular, there was no necrosis or scar formation. The soft tissues were not thinned but appeared to have followed the longitudinal displacement. In conclusion, gradual distraction osteogenesis of the hard palate could be a possible method for lengthening the palate to treat velopharyngeal incompetence.     

Distraction effects on muscle. Leg lengthening studied in rabbits

We investigated changes in the anterior tibial muscle during lengthening of the lower leg in rabbits. In 37 rabbits, an osteotomy of the right middle tibia was performed and was fixed by a unilateral external fixator. The rabbits were randomized into 6 groups. In groups 1, 2, and 3 the tibiae were distracted 0.5 mm/day. In groups 1 and 2, the rabbits were killed after 14 and 28 days of distraction, respectively, and in group 3 after 28 days of distraction, followed by 14 days of rest. Groups 1a, 2a, and 3a served as controls. They were treated similarly as groups 1, 2, and 3, but no distraction was performed. Proliferating cell nuclei were labeled with 5-bromo-2-deoxyuridine and were identified by immunohistochemical staining. The weight of the muscle was measured. During bone lengthening the muscle showed signs of growth, as indicated by increasing weight and number of proliferating cell nuclei. This was observed only during lengthening and it ceased when the lengthening was stopped.     

Inhaled nitric oxide therapy for pulmonary disease in pediatrics

Prostaglandin E2 (PGE2) is an anabolic agent of bone in vivo but the mechanism of its action still remains unclear. The aim of this study was to determine whether the effect of PGE2 on skeleton is mediated by pituitary hormones. Forty female, Sprague-Dawley rats were divided into four groups: baseline control (basal), age-matched intact control (CON), hypophysectomy (HX), and HX + PGE2 (2 mg/kg/day) with 10 animals in each group. The basal group was sacrificed at 2 months of age, and the remaining groups after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double fluorescent-labeled 40 micron-thick sections of the proximal tibia and tibial shaft. Our results show that HX resulted in a cessation of bone growth, a decrease in cancellous bone volume, and cortical bone gain compared with the age-matched, intact CON rats. Compared with the HX group, the HX + PGE2 group had a significantly greater tibial bone density (mean +/- SE, HX + PGE2:1.595 +/- 0.007 versus HX:1.545 +/- 0.013), percent cancellous bone volume (21.4 +/- 2.0 versus 8.41 +/- 1.70), percent cortical bone area (87.2 +/- 0.85 versus 81.7 +/- 0.7), and ratio of cortical area to marrow area (7.14 +/- 0.56 versus 4.52 +/- 0.21). Increased bone masses by PGE2 in the HX animals were accompanied by an increase in the trabecular and endosteal-labeled surface and bone formation rate. The trabecular number and width were increased whereas trabecular separation was decreased in the HX + PGE2 group compared with the HX group (P < 0.05). PGE2 treatment also caused a decrease in the tibial endosteal eroded surface and medullar cavity of the HX animals. In conclusion, this study clearly demonstrates that PGE2 (2 mg/kg/day) in the HX rats increases both cortical and cancellous bones and improves trabecular architecture in the tibia after 6 weeks of treatment. These skeletal alterations are due to a stimulation of bone formation and a suppression of bone resorption activity. These findings suggest that the anabolic effect of PGE2 in bone is independent of pituitary hormones.     

Aprotinin reduces injury of the spinal cord in transient ischemia

OBJECTIVE: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: New Zealand white rabbits (36) of both sexes. METHODS: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30000 KIU as a short intravenous injection after anesthesia, and was followed by 10000 KIU/h by continuous infusion in group 1 (n = 12). Similar volume of saline solution was used in control group of animals (group 2, n = 12). Group 3 of animals (sham group, n = 12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. RESULTS: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53+/-7% of the baseline in all ischemic animals. This was followed by a gradual return to 89+/-8 and 81+/-13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P > 0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P < 0.05). Histological observations were clearly correlated with the neurological findings. CONCLUSION: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

Two reconstructive techniques for flatfoot deformity comparing contact characteristics of the hindfoot joints

The effect of two different methods of reconstruction of flatfoot deformity and the role of the posterior tibial tendon on the contact characteristics of the hindfoot joints were quantified using pressure-sensitive film. Each of 10 cadaver feet was loaded quasi-statically by an axial compressive force to simulate varying loads. First, a specimen was tested intact, then it was tested after sectioning the spring ligament and loading the specimen cyclically to create one type of flatfoot deformity. It was then tested again after reconstructing the deformity. Reconstructions used were the Dillwyn-Evans procedure (bone graft in osteotomy of the calcaneus) or the calcaneocuboid distraction arthrodesis (CCDA). We found that surgically produced flatfoot deformity altered mainly the talonavicular joint, by decreasing its contact area. The Dillwyn-Evans method had less effect on the talonavicular joint (altering 2 of 6 measured parameters) than the CCDA (3 of 6) and more effect on the anteriomedial facet (altering 3 of 6 parameters) than the CCDA (1 of 6). The Dillwyn-Evans method had more effect on the posterior facet (altering 2 of 6 measured parameters) than the CCDA (1 of 6). Function of the posterior tibial tendon had no effect on contact characteristics of the hindfoot joints after either type of reconstruction. These findings are based on measurements using a quasi-statically-loaded foot model at three selected positions, and results may be different with dynamic loading.     

Factors affecting callus distraction in limb lengthening

Factors affecting the process of callus distraction in limb lengthening include the type of osteotomy, timing and rate of distraction, and stability of fixation. Thirty-two rabbits were studied to evaluate the reliability of transverse osteotomy and delayed distraction and to examine the appropriate rates of distraction. Rabbit tibiae were osteotomized subperiosteally and were subjected to slow distraction using a rigid monolateral external fixator. There was a ten-day waiting period before distraction. The animals were divided into three groups according to the rate of distraction (0.35 mm/12 hours, 0.7 mm/12 hours, 1.4 mm/12 hours). The process of callus formation was monitored by soft x-ray. The reliability of delayed distraction after transverse osteotomy was demonstrated by microangiographic study. Even though intramedullar vessels were interrupted by osteotomy at surgery, blood circulation recovered during the waiting period before distraction. Bone lengthening was successful when distraction was carried out at rates of 0.35 mm/12 hours or 0.7 mm/12 hours. The callus filling a distraction gap showed a characteristic zone structure, i.e., one central radiolucent zone and two adjacent sclerotic zones. Microangiographic study demonstrated the continuity of blood vessels under these rates of distraction. Based on the results of these experiments and clinical experiences on 180 bone lengthenings, the authors believe that a waiting period after osteotomy is more practical than achieving immediate distraction after uncertain corticotomy.     

The effect of photon irradiation on blood-brain barrier permeability to methotrexate in mice

Methotrexate was administered by intraperitoneal injection (100 mg/kg) to unirradiated mice, and to mice receiving varying doses of cranial irradiation. The animals were sacrificed 24 hours after injection, and methotrexate assays were performed on brain tissue. No methotrexate was detected in the brains of the unirradiated animals. Detectable levels of methotrexate were present after 2000 rad cranial irradiation, but not after 500 rad, 1000 rad, or 1500 rad. The implications of these findings are discussed.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.     

Influence of aging on cortical and trabecular bone response to estradiol treatment in ovariectomized rats

Three groups (n = 15/group) of 6-, 12- and 30-month-old (mature, old and senescent animals, respectively) female Wistar rats on a diet (6 g/100 g BW/ day) containing 0.8% calcium and 0.8% inorganic phosphorus were studied. Within each group, 10 rats were ovariectomized surgically and 5 injected s.c. with 17 beta-estradiol (E rats, 10 micrograms/kg BW/48 h) and 5 with solvent alone (OVX rats) from day 2 until day 60 after ovariectomy. Five other rats were sham-operated (SH rats) and received solvent only. All rats were killed by exsanguination 60 days after ovariectomy. Neither ovariectomy nor estradiol treatment had a significant effect upon tibial mechanical properties in 6-, 12- and 30-month-old animals. Bone mineral density (BMD) and bone mineral content (BMC) of the distal femur and BMC of the whole femur were decreased by ovariectomy in 6- and 12-month-old rats, but were not different in the SH and E groups. In senescent animals, in which the lowest BMD and BMC were measured, estradiol treatment was more effective in increasing these parameters than in adult and old rats. Image analysis of the distal femoral diaphysis showed that estradiol treatment prevented trabecular bone loss induced by senescence and/or ovariectomy. In each group, urinary deoxypyridinoline excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen-deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. These results indicate that 17 beta-estradiol is particularly effective at preventing high-turnover-induced osteopenia in 30-month-old animals.     

"Primary" orthostatic tremor. 10 clinical electrophysiologic observations

Distraction osteogenesis has been shown to be an effective method of lengthening and augmenting endochondral bone. It has also been applied effectively in the reconstruction of the membranous bones of the craniofacial skeleton. With the accumulation of clinical experience in mandibular distraction, the differences between endochondral and membranous bone distraction have become apparent, especially in the limitations of uniplanar distraction for the three-dimensional reconstruction of the deficient mandible. Distraction of the mandible in a single plane cannot satisfy fully the functional and structural requirements of the patient with malocclusion as well as deficiency of the skeletal and soft tissue. This study reports the development and clinical use of a multiplanar mandibular distraction device with the ability to achieve linear distraction (Z-plane or sagittal), angular distraction (Y-plane or vertical), and transverse distraction (X-plane or coronal). The device contains two independent gear arrangements attached to two arms that extend from the central unit. Therefore, the trajectory of the regenerated bone may be changed during the distraction process. The device also allows manipulation of the various planes of movement independent of each other. Furthermore, the rotational points for the multiplanar distraction devices are located at a single point; therefore only a single osteotomy and two pin sites are required. The multiplanar distraction device allows the surgeon to customize and contour the dimensions of the distraction process by controlling the trajectory of the translation of the regenerated bone.