Sclerostin and DKK1 Inhibition Preserves and Augments Alveolar Bone Volume and Architecture in Rats with Alveolar Bone Loss.

Alveolar bone is a mechanosensitive tissue that provides structural support for teeth. Alveolar bone loss is common with aging, menopause, tooth loss, and periodontitis and can lead to additional tooth loss, reduced denture fixation, and challenges in placing dental implants. The current studies suggest that sclerostin and DKK1, which are established osteocyte-derived inhibitors of bone formation, contribute to alveolar bone loss associated with estrogen ablation and edentulism in rats. Estrogen-deficient ovariectomized rats showed significant mandibular bone loss that was reversed by systemic administration of sclerostin antibody (SAB) alone and in combination with DKK1 antibody (DAB). Osteocytes in the dentate and edentulous rat maxilla expressed Sost (sclerostin) and Dkk1 (DKK1) mRNA, and molar extraction appeared to acutely increase DKK1 expression. In a chronic rat maxillary molar extraction model, systemic SAB administration augmented the volume and height of atrophic alveolar ridges, effects that were enhanced by coadministering DAB. SAB and SAB+DAB also fully reversed bone loss that developed in the opposing mandible as a result of hypo-occlusion. In both treatment studies, alveolar bone augmentation with SAB or SAB+DAB was accompanied by increased bone mass in the postcranial skeleton. Jaw bone biomechanics showed that intact sclerostin-deficient mice exhibited stronger and denser mandibles as compared with wild-type controls. These studies show that sclerostin inhibition, with and without DKK1 coinhibition, augmented alveolar bone volume and architecture in rats with alveolar bone loss. These noninvasive approaches may have utility for the conservative augmentation of alveolar bone.

Growth of the maxillary sinus in children and adolescents: A longitudinal study.

Maxillary sinus volumetric and surface area data and growth models from longitudinal samples of children and adolescents are presented. Cone-beam radiographic CT scans from two small retrospective longitudinal samples, one from the Baylor College of Dentistry, Dallas, TX (N=17, 12 females, 5 males, 10.9-17.4 years) and one from a group private orthodontic practice in Nevada (N=15, 9 females, 6 males, 6.4-13.4 years) were used to collect maxillary sinus volumes and surface areas from each individual imaged at two times separated by variable intervals. Volume and surface area values were collected in Analyze® (Mayo Clinic) and growth models were produced in MLwiN®, a multi-level modeling program. There is a large degree of inter-individual variation. Surface area and surface-area-to-volume ratio (SA:V) changes are particularly variable. Growth models suggest linear growth in both volume and surface area, without growth spurts.

A novel way to statistically analyze morphologic changes in Dmp1-null osteocytes.

Recent studies have revealed multiple roles of osteocytes in bone metabolism. However, detailed analyses of the embedded osteocytes in bone structure are still limited because of the high mineral content around these cells. In this study, we developed an innovative technique, the "FITC-Imaris technique", which combines FITC ([2, 5]-Fluorescein isothiocyanate), confocal microscopy and Imaris software. With this method, we could not only visualize the 3-D morphology of embedded osteocytes, but more importantly, we were able to statistically quantitate the osteocyte structure in the cell surface area, total cell volume, and dendrite numbers. Furthermore, we made a side-by-side comparison of the new method with the acid-etched SEM imaging technique, a common imaging method for studies of osteocyte morphology with a much smaller cell depth (< 3 µm). Finally, we used the FITC-Imaris technique to show both the morphological and statistical differences in the osteocyte structure between the Dmp1-null mice (the osteomalacia model) and their age-matched control littermates. We expect that this newly developed technique will become a powerful tool to disclose more roles that osteocytes play in bone health and diseases.

Variations in cortical material properties throughout the human dentate mandible.

Material properties and their variations in individual bone organs are important for understanding bone adaptation and quality at a tissue level, and are essential for accurate mechanical models. Yet material property variations have received little systematic study. Like all other material property studies in individual bone organs, studies of the human mandible are limited by a low number of both specimens and sampled regions. The aims of this study were to determine: 1) regional variability in mandibular material properties, 2) the effect of this variability on the modeling of mandibular function, and 3) the relationship of this variability to mandibular structure and function. We removed 31 samples on both facial and lingual cortices of 10 fresh adult dentate mandibles, measured cortical thickness and density, determined the directions of maximum stiffness with a pulse transmission ultrasonic technique, and calculated elastic properties from measured ultrasonic velocities. Results showed that each of these elastic properties in the dentate human mandible demonstrates unique regional variation. The direction of maximum stiffness was near parallel to the occlusal plane within the corpus. On the facial ramus, the direction of maximum stiffness was more vertically oriented. Several sites in the mandible did not show a consistent direction of maximum stiffness among specimens, although all specimens exhibited significant orthotropy. Mandibular cortical thickness varied significantly (P < 0.001) between sites, and decreased from 3.7 mm (SD = 0.9) anteriorly to 1.4 mm posteriorly (SD = 0.1). The cortical plate was also significantly thicker (P < 0.003) on the facial side than on the lingual side. Bone was 50-100% stiffer in the longitudinal direction (E(3), 20-30 GPa) than in the circumferential or tangential directions (E(2) or E(1); P < 0.001). The results suggest that material properties and directional variations have an important impact on mandibular mechanics. The accuracy of stresses calculated from strains and average material properties varies regionally, depending on variations in the direction of maximum stiffness and anisotropy. Stresses in some parts of the mandible can be more accurately calculated than in other regions. Limited evidence suggests that the orientations and anisotropies of cortical elastic properties correspond with features of cortical bone microstructure, although the relationship with functional stresses and strains is not clear.

Edentulation alters material properties of cortical bone in the human mandible.

Ridge resorption following edentulation has been documented clinically, but the effects of tooth loss on the material properties of mandibular cortical bone have received little study. Material properties and their structural basis are essential for our understanding of bone quality in the edentulous mandible and are of interest as a tissue-level model for functional adaptation. This study's aim was to determine material property variability in the edentulous mandible, and to compare it with data from a previous study of dentate mandibles. Forty-four cortical samples were removed from each of 10 adult fresh edentulous mandibles. Cortical thickness and density were measured. Material properties were calculated from ultrasonic velocities. Mandibular cortical bone in the edentulous mandibles differed from that of dentate mandibles in cortical thickness, elastic and shear moduli, anisotropy, and orientation of the axis of maximum stiffness. These results suggest that cortical microstructural changes accompany ridge resorption following edentulation.

Accuracy of elastic property measurement in mandibular cortical bone is improved by using cylindrical specimens.

Ultrasonic determination of elastic properties in human craniofacial cortical bone is problematic because of a lack of information about the principal material axes, and because the cortex is often thinner than in long bones. This study investigated solutions that permit reasonable determination of elastic properties in the human mandible. We tested whether ultrasonic velocities could be reliably measured in cylindrical samples of aluminum and mandibular bone, and the effects of reduced specimen thickness. Results indicted that (1) varying shape had minimal effects on ultrasonic velocities or derived elastic properties, and (2) ultrasonic velocities have relatively increased measurement error as propagation distances decreased. The increased error in velocity measurements of mandibular cortical specimens of less than 1.2 mm in thickness should be considered when assessing the reliability of single measurements.

Elastic properties and masticatory bone stress in the macaque mandible.

One important limitation of mechanical analyses with strain gages is the difficulty in directly estimating patterns of stress or loading in skeletal elements from strain measurements. Because of the inherent anisotropy in cortical bone, orientation of principal strains and stresses do not necessarily coincide, and it has been demonstrated theoretically that such differences may be as great as 45 degrees (Cowin and Hart, 1990). Likewise, relative proportions of stress and strain magnitudes may differ. This investigation measured the elastic properties of a region of cortical bone on both the buccal and lingual surfaces of the lower border of the macaque mandible. The elastic property data was then combined with macaque mandibular strain data from published and a new in vivo strain gage experiment to determine directions and magnitudes of maximum and minimum principal stresses. The goal was to compare the stresses and strains and assess the differences in orientation and relative magnitude between them. The main question was whether these differences might lead to different interpretations of mandibular function. Elastic and shear moduli, and Poisson's ratios were measured using an ultrasonic technique from buccal and lingual cortical surfaces in 12 macaque mandibles. Mandibular strain gage data were taken from a published set of experiments (Hylander, 1979), and from a new experiment in which rosette strain gauges were fixed to the buccal and lingual cortices of the mandibular corpus of an adult female Macaca fascicularis, after which bone strain was recorded during mastication. Averaged elastic properties were combined with strain data to calculate an estimate of stresses in the mandibular corpus. The elastic properties were similar to those of the human mandibular cortex. Near its lower border, the macaque mandible was most stiff in a longitudinal direction, less stiff in an inferosuperior direction, and least stiff in a direction normal to the bone's surface. The lingual aspect of the mandible was slightly stiffer than the buccal aspect. Magnitudes of stresses calculated from average strains ranged from a compressive stress of -16.00 GPa to a tensile stress of 8.84 GPa. The orientation of the principal stresses depended on whether the strain gage site was on the working or balancing side. On the balancing side of the mandibles, maximum principal stresses were oriented nearly perpendicular to the lower border of the mandible. On the working side of the mandibles, the orientation of the maximum principal stresses was more variable than on the balancing side, indicating a larger range of possible mechanisms of loading. Near the lower border of the mandible, differences between the orientation of stresses and strains were 12 degrees or less. Compared to ratios between maximum and minimum strains, ratios between maximum and minimum stresses were more divergent from a ratio of 1.0. Results did not provide any major reinterpretations of mandibular function in macaques, but rather confirmed and extended existing work. The differences between stresses and strains on the balancing side of the mandible generally supported the view that during the power stroke the mandible was bent and slightly twisted both during mastication and transducer biting. The calculated stresses served to de-emphasize the relative importance of torsion. On the working side, the greater range of variability in the stress analysis compared to the strain analysis suggested that a more detailed examination of loadings and stress patterns in each individual experiment would be useful to interpret the results. Torsion was evident on the working side; but in a number of experiments, further information was needed to interpret other superimposed regional loading patterns, which may have included parasagittal bending and reverse parasagittal bending.

Force level and strain patterns during bilateral mandibular osteodistraction.

PURPOSE: Recent reports have demonstrated that device orientation is important during mandibular distraction osteogenesis. The purpose of this study was to evaluate the force level and strain patterns on the mandible during bilateral osteodistraction with devices oriented either parallel to the body of the mandible or parallel to the sagittal axis of distraction. MATERIALS AND METHODS: Five unembalmed human cadaver mandibles were placed in a specially designed apparatus for stabilization of the proximal segments during distraction. A force transducer was attached to the lateral aspect of the inferior ramus, and strain gauges were attached to the mandibular bone segments proximal and distal to the distraction device. Lateral force and bone strains were then measured at 5 and 10 mm of distraction. Osteodistraction proceeded first with the devices placed parallel to the mandibular body, then parallel to the axis of distraction. RESULTS: Significantly greater lateral forces were seen when the devices were oriented parallel to the mandibular body. With this device orientation, increased tensile strains were seen at the labial symphysis and medial ramus, and increased compressive strains were found at the lingual symphysis and lateral ramus. However, when the devices were oriented parallel to the axis of distraction, the forces and strains were not detected. CONCLUSIONS: The results suggest that device orientation has important biomechanical effects on lateral forces and strain patterns during mandibular osteodistraction.

Normal masticatory performance in young adults and children.

Previous studies have paid little attention to either the development or sexual dimorphism of masticatory performance. The aim of this study was to measure and compare the masticatory performance of adults and children. Forty-seven healthy and normal individuals (15 adult men, 15 adult women, 15 young girls and 2 young boys) were selected, based on their occlusion, temporomandibular joint function, skeletal classification, and the state of their dentition. Masticatory performance was evaluated by the individual's ability to break down a standardized bolus. Cuttersil impression material was chewed for 20 strokes, spat out, dried, and passed through a series of seven sieves. The Rosin-Rammler equation was used to calculate the median particle size and broadness of particle distribution. Measurements of dentitional surface area, contact area, bite force, mandibular morphology, and body size were also taken as covariates. The results showed significant differences in masticatory performance among the three larger groups; men performed best, followed by women then girls. Multiple regression analyses showed that body size was the most important variable associated with differences in masticatory performance. Adjusting for weight eliminated the group differences. Body size, together with the occlusal contact area of the posterior teeth and the bite force, explained 60-72 percent of the variation in performance. Contact area, posterior ramus height, and bite force explained differences between men and women, but differences between adults and children remained.

Structural properties of mandibular bone following application of a bone plate.

PURPOSE: Similarities in strain patterns between long bones and the mandible suggest that plates may induce stress shielding, resulting in deleterious long-term changes. This study is an investigation of the use of bone plates on the mandible in four adult rhesus monkeys. MATERIAL AND METHODS: A stainless steel plate was attached facially along the inferior border of each mandibular corpus. On the left, a thick (2.5-mm) plate was engaged with four screws. On the right, a thin (0.5-mm) plate was attached with one screw. Monkeys were killed a year after plate placement. At the beginning and end of the experiments, bone strain was recorded inferior to each bone plate during evoked maximal incisal clenching. After death, bone was removed from the mandibles around and under the plates and examined. Gross dimensions and density were measured. An ultrasonic technique was used to measure the material properties, including the elastic and shear moduli. RESULTS: Bone strain inferior to the plates was reduced by 34% to 53% after attachment of the thick plates. Little change in strain was found after attachment of the thin plates. However, no significant differences in structural or mechanical measurements, such as density, cortical thickness, elastic and shear moduli, and Poisson's ratios, were detected between the two sides in each monkey. CONCLUSION: Long-term placement of bone plates, and the resulting stress shielding, were found to result in structural changes in the mandibular corpus.

In vitro strain measurements in the condylar process of the human mandible.

Although there have been a number of experimental studies of temporomandibular joint loading, the precise relation between condylar load and condylar strain is incompletely understood. This in vitro study determined the magnitudes and directions of the principal components of strain on the four surfaces of the condylar process of human cadaver mandibles during loading with selected simulated muscle forces, with simultaneous measurement of occlusal and joint forces. Rosette strain gauges were placed on each of the four surfaces and the mandibles were loaded by a load cell to simulate the action of the masseter and medial pterygoid muscles. Force and strain values were measured at five different bite positions and nine different positions of the resultant muscle force. Forces and strain values were highest when the resultant muscle force was closest to the joint and the bite position was furthest from the joint. The ratios of bite force to joint force and the ratios of forces between the two joints conformed to theoretical predictions of many previous models, with the balancing-side joint being loaded more heavily than the working-side joint. At all gauge positions the maximum principal strain was tensile, the minimum principal strain was compressive, and the absolute strain values were correlated with the magnitude of the force on the condyle. However, under the chosen loading regimen, the ratio of compressive to tensile strain differed among the four surfaces. The highest levels of tensile strain occurred on the anterior and lateral surfaces and the highest compressive strain occurred on the posterior surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Elastic properties of human supraorbital and mandibular bone.

Elastic constants, including the elastic modulus, the shear modulus, and Poisson's ratio, were measured on human craniofacial bone specimens obtained from the supraorbital region and the buccal surfaces of the mandibles of unembalmed cadavers. Constants were determined using an ultrasonic wave technique in three directions relative to the surface of each sample: 1) normal, 2) tangential, and 3) longitudinal. Statistical analysis of these elastic constants indicated that significant differences in the relative proportions of elastic properties existed between the regions. Bone from the mandible along its longitudinal axis was stiffer than bone from the supraorbital region. Directional differences in both locations demonstrated that cranial bone was not elastically isotropic. It is suggested that differences in elastic properties correspond to regional differences in function.

Bone strain following application of a rigid bone plate: an in vitro study in human mandibles.

This study evaluated the effect of a bone plate on mandibular bone strain patterns during static loading. A stainless steel bone plate was unilaterally attached to five human mandibles, which were then subjected to static loads of 60 kiloponds. Four strain gauges attached to the cortical bone were used to measure the strain patterns within the mandible both before and after the bone plate was attached. The results showed that statistically significant alterations in the strain patterns occurred following plating of the mandible. The mandible with the plate attached became more stiff, presumably due to the difference in modulus of elasticity between the plate and the bone. However, this increase in stiffness was relatively small when compared with both total strain under load and strain produced by tightening of the bone screws.

Occlusal force and craniofacial biomechanics during growth in rhesus monkeys.

The masticatory muscles in 132 anesthetized male and female rhesus monkeys ranging in age from juvenile to adult were unilaterally stimulated. Muscle forces and speeds were measured with a bite force transducer positioned at the incisors, premolars, and molars during twitch and tetanic contractions. Lateral cephalographs of all animals were used to estimate the orientation and mechanical advantage of the masticatory muscles. Results showed that maximal occlusal forces increased at a greater rate than body weight during growth. However, maximal occlusal forces increased isometrically relative to mandibular length. Mean forces at the incisors ranged from 70.3 newtons (n) in juveniles up to 139.9 n in adult males. Forces at the molars were 2-2.5 times greater than at the incisors. Time-to-peak tension decreased with increasing body size from 44.1 msec in juveniles to 37.4 msec in adult females to 31.0 msec in adult males. Regression analysis showed that adult males have faster muscles than adult females or juveniles even when corrected for body size. Temporalis and masseter orientation was found to change little throughout growth. The mechanical advantage of the masseter and temporalis muscles for producing occlusal forces on the distal molars improved between juveniles and adults, which is contrary to findings of Oyen et al. (Growth 43:174-187, 1979). Among adults, females had a greater mechanical advantage of the masseter muscles than males.

Development of the nose and soft tissue profile.

Cephalometric radiographs from a sample of 64 untreated persons (32 Class I and 32 Class II) were evaluated to determine the amount, direction and timing of facial soft tissue development. Twenty-five parameters were evaluated in the mixed dentition (7 to 9 years), the early permanent dentition (11 to 13 years), and early adulthood (16 to 18 years). Results showed that anteroposterior growth and subsequent increased anterior projection of the nose continued in both males and females after skeletal growth had subsided. However, females had concluded a large proportion of their soft tissue development by age 12 while in males continued growth was noted until age 17 resulting in their having greater soft tissue dimensions for many of the parameters evaluated. During the developmental period, the angular shapes and positional relationships of the nose, lips and chin remained relatively constant for both sexes and was relatively independent of the underlying hard tissues. Treatment planning implications may be drawn from the amounts and timing of the soft tissue development found in this study.

Electromyography of the suprahyoid musculature following mandibular advancement with and without rigid fixation.

The purpose of this investigation was to determine if the activity of the suprahyoid musculature changes following advancement of the mandible and the use of rigid or nonrigid fixation. Ten monkeys underwent mandibular advancement; six underwent 6 weeks of maxillomandibular fixation (MMF), and four had rigid fixation without MMF. Electromyography (EMG) of the suprahyoid musculature was performed preoperatively, and at 3, 7, and 10 weeks postoperatively. The results of this study fail to demonstrate an increase in suprahyoid EMG activity following mandibular advancement. Furthermore, there were no differences between the groups with different types of fixation.

Short-term stability and muscle adaptation after mandibular advancement surgery with and without suprahyoid myotomy in juvenile Macaca mulatta.

The purpose of this study was to examine the short-term adaptations that occur within the mandible and anterior digastric muscle complex after mandibular advancement with and without suprahyoid myotomy in 20 juvenile rhesus monkeys. The results showed that the animals that did not undergo myotomy experienced relapse equivalent to 13% of the surgical advancement. Those animals that underwent a myotomy of the digastric muscle complex showed complete stability of the surgical lengthening of the mandible. Both groups of animals grew normally after the fixation period when compared to age-matched control animals. Analysis of adaptations within the digastric muscle complex was performed with the use of radiopaque muscle and tendon markers. The results showed an immediate lengthening of the entire digastric muscle complex with mandibular advancement surgery in the group that underwent advancement without myotomy. Further analysis showed that most lengthening in these animals occurred at the connective tissue interfaces of the complex--at the muscle-bone and muscle-tendon interfaces. No significant changes in sarcomere or fiber length were found in the group that did not undergo myotomy, although there was a significant shortening of muscle fibres resulting from loss of serial sarcomeres in the myotomy group. Comparison of histochemical characteristics of the anterior digastric muscle before and after surgery revealed the following findings: (1) there were no significant differences in percentage of composition between control and experimental muscles; (2) despite fixation of the jaws and myotomy, there was no evidence of atrophy of the anterior digastric muscle at any experimental interval; and (3) the type I fibers of the anterior digastric muscle underwent significant stretch-induced hypertrophy after lengthening. The results of this study support the hypothesis that tension produced by stretching of the connective tissues associated with the digastric muscle complex can contribute to postsurgical relapse of the surgically advanced mandible. However, no adverse effect on future growth of the mandible was observed from stretching the digastric muscle complex by mandibular advancement surgery in juvenile subjects.

A comparison of stimulated bite force after mandibular advancement using rigid and nonrigid fixation.

This study evaluated maximum stimulated molar bite force following advancement of the mandible in 17 adult Macaca mulatta using rigid and nonrigid fixation techniques. Cephalometric analysis was also performed to determine the amount of proximal segment rotation. Analysis of the bite force showed the animals whose mandibles were advanced using rigid fixation to have significantly greater bite force at six weeks postsurgery when compared to those animals who underwent mandibular advancement and six weeks of maxillomandibular fixation. By the ninth postoperative week, there was no longer any significant difference between the two groups, indicating a rapid recovery of muscle function in the animals whose mandibles were immobilized following advancement. Both groups, however, had significant decreases in bite force at 12 weeks postsurgery when compared to preoperative values. Neither group had a significant amount of proximal segment rotation from the surgery.

Adaptation of the suprahyoid muscle complex to mandibular advancement surgery.

The suprahyoid musculature has been implicated as one of the major factors responsible for relapse after mandibular advancement surgery. Previous studies have also indicated that the muscle and connective tissues comprising the suprahyoid complex must adapt to increased length brought about by mandibular advancement for skeletal stability to be achieved. The purpose of this study was to provide quantitative data concerning the immediate changes and long-term adaptations that take place within the suprahyoid complex over a 2-year period after mandibular advancement. Mandibular advancement was performed on ten adult Macaca mulatta monkeys with and without suprahyoid myotomy (n = 5/group). Six animals were used as controls. Mandibular length and changes in the length of the various anatomic regions of the suprahyoid complex were evaluated radiographically with the aid of radiopaque bone, muscle, and tendon markers implanted preoperatively. The results for the nonmyotomy group showed that the suprahyoid complex was elongated approximately two thirds the amount of mandibular lengthening, the major immediate adaptations within the suprahyoid complex after the surgical procedure occurred at the muscle-bone interface and the muscle-tendon interface, the change in length at the muscle-tendon junction was maintained throughout the 2-year follow-up period, indicating that significant long-term adaptations took place primarily at that location, and no significant short-term changes or long-term adaptations were seen within the anterior digastric muscle or the intermediate digastric tendon. Within the myotomy group, it was found that the suprahyoid complex recoiled immediately after myotomy such that the anterior belly of the digastric muscle became separated from the advanced distal mandibular segment by more than twice the amount of mandibular lengthening, the anterior digastric muscle remained essentially at this posterior position throughout the 2-year follow-up period, and though not significant, there was a trend for a decrease in the length of the anterior digastric muscle belly. On the basis of these results, it was concluded that both short-term changes and long-term adaptations to lengthening of the suprahyoid complex as a result of mandibular lengthening occur primarily within the connective tissues comprising the muscle-tendon and muscle-bone interfaces, not within the muscle fibers themselves.

Occlusal force after mandibular advancement in adult rhesus monkeys.

Maxillofacial surgery not only alters facial appearance and occlusion but also affects the morphology, physiology, and biomechanics of the craniofacial skeleton and the muscles of mastication. This study was performed to evaluate one aspect of craniofacial function--maximum stimulated bite force (BF)--after mandibular advancement. BF in the molar region was measured with a transducer during muscle stimulation in 63 rhesus monkeys that had been divided into two groups: a control group of various ages and sexes (n = 50); and an experimental sample of 13 monkeys that had undergone mandibular advancement via C-osteotomy at least one year prior to BF measurement. Biomechanical analysis of lateral cephalograms was performed to estimate the amount of the change in BF in the experimental group that could be attributed to alteration of craniofacial form. Regression analysis demonstrated a significant relation between molar bite force and weight in control animals (r = 0.94). In the monkeys that underwent surgery, BF values were an average of 16.7% less than those found for the control animals relative to body weight. However, the biomechanical analyses suggested a smaller and less variable BF loss in the operated monkeys (11.6%). These results indicate a greater and more variable change in BF following mandibular advancement than would be predicted on the basis of biomechanical considerations.