Mechanical compensation in the evolution of the early hominin feeding apparatus.

Australopiths, a group of hominins from the Plio-Pleistocene of Africa, are characterized by derived traits in their crania hypothesized to strengthen the facial skeleton against feeding loads and increase the efficiency of bite force production. The crania of robust australopiths are further thought to be stronger and more efficient than those of gracile australopiths. Results of prior mechanical analyses have been broadly consistent with this hypothesis, but here we show that the predictions of the hypothesis with respect to mechanical strength are not met: some gracile australopith crania are as strong as that of a robust australopith, and the strength of gracile australopith crania overlaps substantially with that of chimpanzee crania. We hypothesize that the evolution of cranial traits that increased the efficiency of bite force production in australopiths may have simultaneously weakened the face, leading to the compensatory evolution of additional traits that reinforced the facial skeleton. The evolution of facial form in early hominins can therefore be thought of as an interplay between the need to increase the efficiency of bite force production and the need to maintain the structural integrity of the face.

Biomechanics of the mandible of Macaca mulatta during the power stroke of mastication: Loading, deformation, and strain regimes and the impact of food type.

Mandible morphology has yet to yield definitive information on primate diet, probably because of poor understanding of mandibular loading and strain regimes, and overreliance on simple beam models of mandibular mechanics. We used a finite element model of a macaque mandible to test hypotheses about mandibular loading and strain regimes and relate variation in muscle activity during chewing on different foods to variation in strain regimes. The balancing-side corpus is loaded primarily by sagittal shear forces and sagittal bending moments. On the working side, sagittal bending moments, anteroposterior twisting moments, and lateral transverse bending moments all reach similar maxima below the bite point; sagittal shear is the dominant loading regime behind the bite point; and the corpus is twisted such that the mandibular base is inverted. In the symphyseal region, the predominant loading regimes are lateral transverse bending and negative twisting about a mediolateral axis. Compared with grape and dried fruit chewing, nut chewing is associated with larger sagittal and transverse bending moments acting on balancing- and working-side mandibles, larger sagittal shear on the working side, and larger twisting moments about vertical and transverse axes in the symphyseal region. Nut chewing is also associated with higher minimum principal strain magnitudes in the balancing-side posterior ramus; higher sagittal shear strain magnitudes in the working-side buccal alveolar process and the balancing-side oblique line, recessus mandibulae, and endocondylar ridge; and higher transverse shear strains in the symphyseal region, the balancing-side medial prominence, and the balancing-side endocondylar ridge. The largest food-related differences in maximum principal and transverse shear strain magnitudes are in the transverse tori and in the balancing-side medial prominence, extramolar sulcus, oblique line, and endocondylar ridge. Food effects on the strain regime are most salient in areas not traditionally investigated, suggesting that studies seeking dietary effects on mandible morphology might be looking in the wrong places.

Divided zygoma in Holocene human populations from Northern China.

OBJECTIVES: Divided zygoma (DZ) occurs in contemporaneous human populations, with the highest incidences in people from East Asia and Southern Africa. The present study examines the prevalence and variation of this condition in the Holocene populations of Northern China for the first time. METHODS: In this study, 1145 skulls from various human populations living in Northern China from the Neolithic Age to recent dynasties (5000-300 years BP) were examined. Specifically, cranial measurements and a CT scan were conducted to quantify craniofacial morphology. RESULTS: Fifteen skulls were identified with DZ, revealing an overall prevalence of 1.3% in the collection, while it was determined to be higher in North Asian and Northeast Asian regional groups. In skulls with unilateral DZ, the superior division of the zygoma was generally slender, while the inferior division of the zygoma was more robust. In skulls with bilateral DZ, the maxillae were generally more laterally extended. Moreover, unilateral DZ skulls displayed differences in cortical bone thickness between two sides of the facial skeleton. DISCUSSION: In context, the distribution pattern within these data points toward a greater prevalence of the DZ phenotype in North and Northeast Asian regional groups, suggesting a hypothesis that the DZ trait is more frequent in populations characterized by flat and broad faces. Accordingly, further studies into the DZ condition will deepen our understanding of developments in plasticity, variation, and recent evolution of the human cranium.

Two distalization methods compared in a novel patient-specific finite element analysis.

INTRODUCTION: Orthodontic mini-implants aid in the correction of distocclusions via direct anchorage (pull from mini-implant to teeth) and indirect anchorage (teeth pulled against other teeth anchored by the mini-implant). The aim of this study was to compare stress levels on the periodontal ligament (PDL) of maxillary buccal teeth in direct and indirect distalization against orthodontic mini-implants and accounting for individual variation in maxillary anatomy and biomechanical characteristics of the compact bone. METHODS: A 3D model of the maxilla containing the different components (teeth, PDL, trabecular and cortical bones) was generated from a computed tomographic scan. Cortical bone was divided into several areas according to previously defined zones. Bone stiffness and thickness data, obtained from 11 and 12 cadavers, respectively, were incorporated into the initial model to simulate the individual cortical bone variation at the different locations. Subsequently, a finite element analysis was used to simulate the distalization modalities. RESULTS: Stresses at the buccal, palatal, mesial, and distal surfaces were significantly different between adjacent teeth under stiffness but not thickness variation. In both distalization modalities, low or no significant correlations were found between stress values and corresponding cortical bone thicknesses. High significant and inverted correlations were observed at the first molar between stress amounts and cortical bone stiffness (direct modality: -0.68 < r < -0.72; indirect modality: -0.80 < r < -0.82; P <0.05). CONCLUSIONS: With the use of a novel finite element approach that integrated human data on variations in bone properties, findings suggested that cortical bone stiffness may influence tooth movement more than bone thickness. Significant clinical implications could be related to these findings.

Odontogenic abscesses in rhesus macaques (Macaca mulatta) of Cayo Santiago.

OBJECTIVES: Odontogenic abscesses are one of the most common dental diseases causing maxillofacial skeletal lesions. They affect the individual's ability to maintain the dental structures necessary to obtain adequate nutrition for survival and reproduction. In this study, the prevalence and pattern of odontogenic abscesses in relation to age, sex, matriline, and living periods were investigated in adult rhesus macaque skeletons of the free-ranging colony on Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: The skulls used for this study were from the skeletons of 752 adult rhesus macaques, aged 8-31 years, and born between 1951 and 2000. They came from 66 matrilines ranging from 1 to 88 individuals. Fistulae or skeletal lesions caused by odontogenic abscesses drainage, carious lesions, tooth fractures, tooth loss, and alveolar resorption were evaluated visually. RESULTS: Seventy-two specimens (9.57%) had odontogenic abscesses of varying severity. Males had a significantly higher prevalence than females. The prevalence of odontogenic abscesses in several matrilines was significantly higher than in the population as a whole. Animals born between 1950 and 1965 tended to have a higher prevalence of odontogenic abscesses than those born in later periods. DISCUSSION: These results suggest that oral pathologies, such as dental and periodontal abscesses in rhesus macaques are fairly common, which may indicate familial effects interwoven with ecological and social factors. The closeness of the rhesus and human genomes allows insights to understand of the epidemiology of these diseases in the human population. Further assessment of the role played by environmental and familial factors on rhesus oral health and disease are warranted.

Elevation of a full-thickness mucoperiosteal flap alone accelerates orthodontic tooth movement.

INTRODUCTION: Our objective was to determine whether the elevation of a full-thickness mucoperiosteal flap alone, without cortical cuts, decreases the amount of bone around teeth and accelerates mesial tooth movements. METHODS: The mandibular second premolars of 7 beagle dogs were extracted, and on a randomly selected side, a full-thickness mucoperiosteal buccal flap extending from the distal aspect of the third premolar to the mesial aspect of the first premolar was elevated. The other side did not receive flap surgery. The mandibular third premolars were protracted with orthodontic appliances. Tooth movements were analyzed biweekly over an 8-week period with calipers and radiographs. The amount and density of bone were analyzed using microcomputed tomography; bone remodeling was evaluated with histologic sections. RESULTS: Experimental tooth movements measured intraorally between cusp tips were significantly greater (25.3%) than control tooth movements. The approximate center of resistance measured radiographically also moved significantly more (about 31%) on the experimental than on the control side. The experimental premolar tipped more than the control premolar (10.5° vs 8.7°), but the difference was not statistically significant. The medullary bone volume fraction mesial to the third premolar was significantly less (9.1%) and the bone was significantly less dense (9%) on the experimental side than on the control side. Histology showed no apparent side differences in the numbers of osteoclasts and osteoblasts evident in the medullary bone. CONCLUSIONS: Elevation of a full-thickness mucoperiosteal flap alone (ie, without injury to bone) decreases the amount and density of medullary bone surrounding the tooth and accelerates tooth movement. Due to its limited effects, elevation of a flap alone to increase tooth movements may not be justified.

Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation.

Twist1 is a basic helix-loop-helix-containing transcription factor that is expressed in the dental mesenchyme during the early stages of tooth development. To better delineate its roles in tooth development, we generated Twist1 conditional knockout embryos (Twist2(Cre) (/+);Twist1(fl/fl)) by breeding Twist1 floxed mice (Twist1(fl/fl)) with Twist2-Cre recombinase knockin mice (Twist2(Cre) (/+)). The Twist2(Cre) (/+);Twist1(fl/fl) embryos formed smaller tooth germs and abnormal cusps during early tooth morphogenesis. Molecular and histological analyses showed that the developing molars of the Twist2(Cre) (/+);Twist1(fl/fl) embryos had reduced cell proliferation and expression of fibroblast growth factors 3, 4, 9, and 10 and FGF receptors 1 and 2 in the dental epithelium and mesenchyme. In addition, 3-week-old renal capsular transplants of embryonic day 18.5 Twist2(Cre) (/+);Twist1(fl/fl) molars showed malformed crowns and cusps with defective crown dentin and enamel. Immunohistochemical analyses revealed that the implanted mutant molars had defects in odontoblast differentiation and delayed ameloblast differentiation. Furthermore, in vitro ChIP assays demonstrated that Twist1 was able to bind to a specific region of the Fgf10 promoter. In conclusion, our findings suggest that Twist1 plays crucial roles in regulating tooth development and that it may exert its functions through the FGF signaling pathway.

The mandibles of castrated male rhesus macaques (Macaca mulatta): The effects of orchidectomy on bone and teeth.

OBJECTIVES: The objectives of this study were to evaluate the long-term effects of orchidectomy and low testosterone on the craniofaciodental development and maintenance of skeletal and oral health in rhesus macaques. MATERIALS AND METHODS: Mandibles of four castrated and intact age-matched male rhesus monkeys (Macaca mulatta) from Cayo Santiago were compared for mandibular morphology and teeth, abnormalities, pathology, and cortical bone thickness and density using a digital sliding caliper and analysis of three-dimensional X-ray images. RESULTS: Although all four castrates were generally comparable to intact males in overall mandible and teeth size, there were some significant differences. In the castrates, (1) the distance between the two rami was narrower than in intact males leading to a relatively narrower and longer face; (2) both the mandibular body and ramus had thinner cortical bone leading to less total bone mass; and (3) the canines and molar teeth were slender with lower and less robust tooth cusps. In addition, the alveolar bone of two geriatric castrates was greatly receded with signs of periodontitis more severe than in intact aged males. Old castrates also had severe temporomandibular joint osteoarthritis. DISCUSSION: The findings suggest the importance of testosterone in craniofaciodental development, and maintenance of skeletal and oral health in male macaques. These results suggest that dental health professionals might want to include in their medical history questionnaires whether or not male patients have taken hormone (testosterone) replacement therapy.

Dentate transport discs can be used to reconstruct large segmental mandibular defects.

PURPOSE: This study tested the use of a dentate transport segment for the reconstruction of a large U-shaped defect in the anterior segment of the canine mandible using a novel curved reconstruction plate. The quality and quantity of bone regenerate formed by dentate versus edentulous transport segments were compared. MATERIALS AND METHODS: In 5 adult foxhound dogs, a defect of 70 to 75 mm was created in the canine mandible by excising the mandible anterior to the right and left fourth premolars. Reconstruction was performed by trifocal distraction osteogenesis using a bone transport reconstruction plate (BTRP-02), with 2 transport units being activated simultaneously, one on either side of the defect, 1 dentate and 1 edentulous. Bilateral distraction proceeded at a rate of 1 mm/day until the segments docked against each other in the midline. After 39 to 44 days of consolidation, the animals were euthanized. The quantity and quality of bone regeneration on the 2 sides were compared using micro-computed tomography. RESULTS: The defect reconstruction was successful. The amount and quality of bone formed by the transport segments were similar on the 2 sides. There were no major differences in the bone volume fraction and density of the regenerate bone formed by the 2 transport segments. The bone volume fraction and density of the regenerate bone were considerably lower than those of the host bone in the distal segments, likely owing to the short consolidation period. CONCLUSIONS: Bone transport remains a viable option in reconstructing anterior segmental defects in the mandible. The use of dentate or edentulous transport segments for reconstruction provides options for the surgeon in often highly compromised patients requiring these surgeries.

Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ.

The endocrine hormone fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism and a promising drug for type 2 diabetes. Here we identify FGF21 as a potent regulator of skeletal homeostasis. Both genetic and pharmacologic FGF21 gain of function lead to a striking decrease in bone mass. In contrast, FGF21 loss of function leads to a reciprocal high-bone-mass phenotype. Mechanistically, FGF21 inhibits osteoblastogenesis and stimulates adipogenesis from bone marrow mesenchymal stem cells by potentiating the activity of peroxisome proliferator-activated receptor γ (PPAR-γ). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-γ agonist rosiglitazone. Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration.

Biomechanics of the canine mandible during bone transport distraction osteogenesis.

This study compared biomechanical patterns between finite element models (FEMs) and a fresh dog mandible tested under molar and incisal physiological loads in order to clarify the effect of the bone transport distraction osteogenesis (BTDO) surgical process. Three FEMs of dog mandibles were built in order to evaluate the effects of BTDO. The first model evaluated the mandibular response under two physiological loads resembling bite processes. In the second model, a 5.0 cm bone defect was bridged with a bone transport reconstruction plate (BTRP). In the third model, new regenerated bony tissue was incorporated within the defect to mimic the surgical process without the presence of the device. Complementarily, a mandible of a male American foxhound dog was mechanically tested in the laboratory both in the presence and absence of a BTRP, and mechanical responses were measured by attaching rosettes to the bone surface of the mandible to validate the FEM predictions. The relationship between real and predicted values indicates that the stress patterns calculated using FEM are a valid predictor of the biomechanics of the BTDO procedures. The present study provides an interesting correlation between the stiffness of the device and the biomechanical response of the mandible affected for bone transport.

How does the amount of surgical insult affect bone around moving teeth?

INTRODUCTION: The purpose of this study was to determine how the amount of surgical insult affects the quantity and maturity of dentoalveolar bone around teeth that have been orthodontically moved. METHODS: A split-mouth design with 8 foxhound dogs was used to evaluate bone surrounding maxillary second premolars that were protracted for 15 days and retained for 7 weeks. The maxillary first premolars were extracted, and the interseptal bone was removed to within 1 mm of the second premolars; on the insult (lesser surgical insult) side, buccal and lingual vertical grooves were made in the extraction socket to undermine the mesial root of the second premolar; the insult+ (greater surgical insult) side was flapped and had modified corticotomies extending to, but not through, the lingual cortex 1 mm distal to the distal root, and 3 to 5 mm apical to both roots. Microcomputed tomography analyses were used to evaluate the material density, bone volume fraction, and trabecular characteristics of surrounding bone. Hematoxylin and eosin sections were used to determine osteoclast numbers, bone surface areas, and bone volumes. RESULTS: After 7 weeks of consolidation, there was significantly (P <0.05) less bone on the insult+ side; it was less dense and less mature than the bone on the insult side. Relative to the control bone, bone on the insult+ side was significantly less dense but showed no differences in bone volume. Preliminary histologic evaluations indicated increased numbers of osteoclasts and greater bone surface areas on the insult+ side than the insult side, but no differences in bone volume. CONCLUSIONS: Increased surgical insults produce less dense and less mature bone but have no effect on bone volume at 9 weeks after surgery.

Viewpoints: diet and dietary adaptations in early hominins: the hard food perspective.

Recent biomechanical analyses examining the feeding adaptations of early hominins have yielded results consistent with the hypothesis that hard foods exerted a selection pressure that influenced the evolution of australopith morphology. However, this hypothesis appears inconsistent with recent reconstructions of early hominin diet based on dental microwear and stable isotopes. Thus, it is likely that either the diets of some australopiths included a high proportion of foods these taxa were poorly adapted to consume (i.e., foods that they would not have processed efficiently), or that aspects of what we thought we knew about the functional morphology of teeth must be wrong. Evaluation of these possibilities requires a recognition that analyses based on microwear, isotopes, finite element modeling, and enamel chips and cracks each test different types of hypotheses and allow different types of inferences. Microwear and isotopic analyses are best suited to reconstructing broad dietary patterns, but are limited in their ability to falsify specific hypotheses about morphological adaptation. Conversely, finite element analysis is a tool for evaluating the mechanical basis of form-function relationships, but says little about the frequency with which specific behaviors were performed or the particular types of food that were consumed. Enamel chip and crack analyses are means of both reconstructing diet and examining biomechanics. We suggest that current evidence is consistent with the hypothesis that certain derived australopith traits are adaptations for consuming hard foods, but that australopiths had generalized diets that could include high proportions of foods that were both compliant and tough.

Microwear, mechanics and the feeding adaptations of Australopithecus africanus.

Recent studies of dental microwear and craniofacial mechanics have yielded contradictory interpretations regarding the feeding ecology and adaptations of Australopithecus africanus. As part of this debate, the methods used in the mechanical studies have been criticized. In particular, it has been claimed that finite element analysis has been poorly applied to this research question. This paper responds to some of these mechanical criticisms, highlights limitations of dental microwear analysis, and identifies avenues of future research.

Probabilistic finite element analysis of a craniofacial finite element model.

We employed a probabilistic finite element analysis (FEA) method to determine how variability in material property values affects stress and strain values in a finite model of a Macaca fascicularis cranium. The material behavior of cortical bone varied in three ways: isotropic homogeneous, isotropic non-homogeneous, and orthotropic non-homogeneous. The material behavior of the trabecular bone and teeth was always treated as isotropic and homogeneous. All material property values for the cranium were randomized with a Gaussian distribution with either coefficients of variation (CVs) of 0.2 or with CVs calculated from empirical data. Latin hypercube sampling was used to determine the values of the material properties used in the finite element models. In total, four hundred and twenty six separate deterministic FE simulations were executed. We tested four hypotheses in this study: (1) uncertainty in material property values will have an insignificant effect on high stresses and a significant effect on high strains for homogeneous isotropic models; (2) the effect of variability in material property values on the stress state will increase as non-homogeneity and anisotropy increase; (3) variation in the in vivo shear strain values reported by Strait et al. (2005) and Ross et al. (2011) is not only due to variations in muscle forces and cranial morphology, but also due to variation in material property values; (4) the assumption of a uniform coefficient of variation for the material property values will result in the same trend in how moderate-to-high stresses and moderate-to-high strains vary with respect to the degree of non-homogeneity and anisotropy as the trend found when the coefficients of variation for material property values are calculated from empirical data. Our results supported the first three hypotheses and falsified the fourth. When material properties were varied with a constant CV, as non-homogeneity and anisotropy increased the level of variability in the moderate-to-high strains decreased while the level of variability in the moderate-to-high stresses increased. However, this is not the pattern observed when CVs calculated from empirical data were applied to the material properties where the lowest level of variability in both stresses and strains occurred when the cranium was modeled with a low level of non-homogeneity and anisotropy. Therefore, when constant material property variability is assumed, inaccurate trends in the level of variability present in modest-to-high magnitude stresses and strains are produced. When the cranium is modeled with the highest level of accuracy (high non-homogeneity and anisotropy) and when randomness in the material properties is calculated from empirical data, there is a large level of variability in the significant strains (CV=0.369) and a low level of variability in the modest-to-high magnitude stresses (CV=0.150). This result may have important implications with regard to the mechanical signals driving bone remodeling and adaptation through natural selection.

Bone regeneration and docking site healing after bone transport distraction osteogenesis in the canine mandible.

PURPOSE: Bone transport distraction osteogenesis provides a promising alternative to traditional grafting techniques. However, existing bone transport distraction osteogenesis devices have many limitations. The purpose of this research was to test a new device, the mandibular bone transport reconstruction plate, in an animal model with comparable mandible size to humans and to histologically and mechanically examine the regenerate bone. MATERIALS AND METHODS: Eleven adult foxhounds were divided into an unreconstructed control group of 5 animals and an experimental group of 6 animals. In each animal, a 34-mm segmental defect was created in the mandible. The defect was reconstructed with a bone transport reconstruction plate. Histologic and biomechanical characteristics of the regenerate and unrepaired defect were analyzed and compared with bone on the contralateral side of the mandible after 4 weeks of consolidation. RESULTS: The reconstructed defect was bridged with new bone, with little bone in the control defect. Regenerate density and microhardness were 22.3% and 42.6%, respectively, lower than the contralateral normal bone. Likewise, the anisotropy of the experimental group was statistically lower than in the contralateral bone. Half the experimental animals showed nonunion at the docking site. CONCLUSION: The device was very stable and easy to install and activate. After 1 month of consolidation, the defect was bridged with new bone, with evidence of active bone formation. Regenerate bone was less mature than the control bone. Studies are underway to identify when the regenerate properties compare with normal bone and to identify methods to augment bone union at the docking site.

The feeding biomechanics and dietary ecology of Australopithecus africanus.

The African Plio-Pleistocene hominins known as australopiths evolved a distinctive craniofacial morphology that traditionally has been viewed as a dietary adaptation for feeding on either small, hard objects or on large volumes of food. A historically influential interpretation of this morphology hypothesizes that loads applied to the premolars during feeding had a profound influence on the evolution of australopith craniofacial form. Here, we test this hypothesis using finite element analysis in conjunction with comparative, imaging, and experimental methods. We find that the facial skeleton of the Australopithecus type species, A. africanus, is well suited to withstand premolar loads. However, we suggest that the mastication of either small objects or large volumes of food is unlikely to fully explain the evolution of facial form in this species. Rather, key aspects of australopith craniofacial morphology are more likely to be related to the ingestion and initial preparation of large, mechanically protected food objects like large nuts and seeds. These foods may have broadened the diet of these hominins, possibly by being critical resources that australopiths relied on during periods when their preferred dietary items were in short supply. Our analysis reconciles apparent discrepancies between dietary reconstructions based on biomechanics, tooth morphology, and dental microwear.

Vacuum-induced Suction Stimulates Increased Numbers of Blood Vessels in Healthy Dog Gingiva.

UNLABELLED:  This study was designed to determine if vacuum-induced suction increased the number of blood vessels in healthy dog gingiva as a prelude to future studies testing vacuum therapy for improving local blood supply and controlling periodontal disease. METHODS: The buccal gingiva of five dogs was treated with subatmospheric pressure for 5 days, with untreated tissues acting as controls. Biopsies were analyzed for vascular endothelial growth factors (VEGF) and blood vessels were counted. RESULTS: VEGF and vessel numbers were elevated in treatment groups compared to controls (P < 0.05). CONCLUSION: A single daily application of subatmospheric pressure might be beneficial for healing damaged or diseased gingival tissues. .

Elastic anisotropy and off-axis ultrasonic velocity distribution in human cortical bone.

Elastic structure in cortical bone is usually simplified as orthotropic or transversely isotropic, which allows estimates of three-dimensional technical constants from ultrasonic and density measurements. These elastic property estimates can then be used to study phenotypic changes in cortical bone structure and function, and to create finite element models of skeletal structures for studies of organismal variation and functional adaptation. This study examines assumptions of orthotropic or transversely isotropic material structure in cortical bone through the investigation of off-axis ultrasonic velocities in the cortical plane in 10 samples each from a human femur, mandible and cranium. Longitudinal ultrasonic velocities were measured twice through each bone sample by rotating the perimeter of each sample in 1 ° angular intervals between two ultrasonic transducers. The data were fit to sine curves f(x)=(A × sin(x + B) + C) and the goodness of fit was examined. All the data from the femur fit closely with the ideal sine curve model, and all three coefficients were similar among specimens, indicating similar elastic properties, anisotropies and orientations of the axes of maximum stiffness. Off-axis ultrasonic velocities in the mandible largely fit the sine curve model, although there were regional variations in the coefficients. Off-axis ultrasonic velocities from the cranial vault conformed to the sine curve model in some regions but not in others, which shows an irregular and complex pattern. We hypothesize that these variations in ultrasonic velocities reflect variations in the underlying bulk microstructure of the cortical bone, especially in the three-dimensional patterns of osteonal orientation and structure. Elastic property estimates made with ultrasonic techniques are likely valid in the femur and mandible; errors in estimates from cranial bone need to be evaluated regionally. Approximate orthotropic structure in bulk cortical bone specimens should be assessed if ultrasound is used to estimate three-dimensional elastic properties.