Testing the biomechanical optimality of the wall thickness of limb bones in the red fox (Vulpes vulpes)

The optimum for the ratio K of the internal to external diameter of a marrow-filled tubular bone with minimum mass designed to withstand a given type of strength (yield/fatigue, stiffness, fracture or impact) depends on Q = rhom/rhob only, where rhom and rhob are the densities of marrow and bone. With computer-assisted evaluation of radiographs of 62 femurs in the red fox (Vulpes vulpes) we measured the values of K. The mean and standard deviation of K are 0.68 and 0.036, and K changes in the rather wide range from 0.59 to 0.74. Accepting the assumption of earlier authors that Q = 0.50 or 0.44, our data would support the hypothesis that the fox femurs are optimized to withstand yield, fatigue or stiffness strengths. However, since the Q-values are unknown, the possibility cannot be excluded that any studied fox bone with an appropriately selected Q-value is optimized for any strength type. Assuming Q = 0.50 or 0.44, the relative mass increments mu of the investigated fox bones are smaller than 5% under all four mechanical conditions. The evolutionary relevance of such tiny mu-values is questionable.     

The many adaptations of bone

Studies concerned with the "adaptations" in bones usually deal with modelling taking place during the individual's lifetime. However, many adaptations are produced over evolutionary time. This survey samples some adaptations of bone that may occur over both length scales, and tries to show whether short- or long-term adaptation is important. (a) Woven and lamellar bone. Woven bone is less mechanically competent than lamellar bone but is frequently found in bones that grow quickly. (b) Stress concentrations in bone. Bone is full of cavities that potentially may act as stress concentrators. Usually these cavities are oriented to minimise their stress-concentrating effect. Furthermore, the "flow" of lamellae round the cavities will still further reduce their stress-concentrating effect, but the elastic anisotropy of bone will, contrarily, tend to enhance it in normal loading situations. (c) Stiffness versus toughness. The mineral content of bone is the main determinant of differences in mechanical properties. Different bones have different mineral contents that optimise the mix of stiffness and toughness needed. (d) Synergy of whole bone architecture and material properties. As bone material properties change during growth the architecture of the whole bone is modified concurrently, to produce an optimum mechanical behaviour of the whole bone. (e) Secondary remodelling. The formation of secondary osteones in general weakens bone. Various suggestions that have been put forward to account for secondary remodelling: enabling mineral homeostasis; removing dead bone; changing the grain of the bone; taking out microcracks. (f) The hollowness of bones. It is shown how the degree of hollowness is adapted to the life of the animal.     

Potentialities of temporal bone CT in the diagnosis of chronic purulent otitis media and its complications

Temporal bone CT was used to examine a group of 87 patients with chronic purulent otitis media (103 temporal bones). The patients' age ranged from 2 to 74 years. A scheme was developed and proposed to evaluate the temporal bone by CT. The CT signs of chronic purulent otitis media uncomplicated by cholesteatoma and those of cholesteatomic purulent otitis were identified. The CT symptomatology of chronic purulent otitis includes: sclerotic changes in the bone tissue of the mastoid process, impaired pneumatization of the cavities of the middle ear, including the tympanic cavity, destructive changes in auditory ossicles, carious changes in the walls of the cavities of the middle ear. The CT semiotics of cholesteatoma depends on its site and spread into the temporal bone and includes as follows: deformation of the epitympanum due to soft tissue mass-induced destruction of the lateral wall; the dilated entrance into the antrum; the presence of a cavity with the sclerosed walls in the antromastoid area; carious changes in the auditory ossicles; the displacement of a chain of ossicles medially or laterally in relation to the initial site of cholesteatoma. CT reflects carious changes in the walls of the cavities of the middle ear, including the roof and labyrinthine wall of the tympanum, which allows labyrinthine fistula and intracranial cholesteatomic complications. The study of the temporal bone by the proposed scheme may reveal anomalies and the specific features of its structure: the presentation of the sigmoid sinus, the high elevation of the bulb of the jugular vein, diverticulum of the latter, the low standing of the bottom of the ACH.     

Comparison of bone formed in transplants of isolated scapular and vertebral osteoblasts

To compare the properties of osteoblasts from various endochondrilia bones, scapular and calvarial osteoblasts were intramuscularly transplanted in "sandwiches" made of devitalized calvarial vaults. The structure of transplants produced by both types of bone cells appeared similar. In 4 week-old transplants woven bone with numerous osteoclasts predominated. The area occupied on the cross-sections of transplants by bone tissue was considerably larger than that of the bone marrow cavities. Transplants of 8-week-duration contained mainly cancellous bone, the number of osteoblasts was low and the area taken by medullary space was larger than that of bone tissue. This finding indicates that either osteoblasts from various endochondrlia bones have similar properties or that the possible differences in intrinsic features of these osteoblasts were masked by the conditions of transplantation.     

On shear properties of trabecular bone under torsional loading: effects of bone marrow and strain rate

To further improve our understanding of trabecular bone mechanical behavior in torsion, our objective was to determine the effects of strain rate, apparent density, and presence of bone marrow on trabecular bone shear material properties. Torsion tests of cylindrical trabecular bone specimens from sheep lumbar vertebrae with and without bone marrow were conducted. The bones with marrow were divided into two groups and tested at shear strain rates of 0.002 and 0.05s(-1) measured at the specimen perimeter. The bones without marrow were divided into three groups and tested at shear strain rates of 0.002, 0.015, and 0.05s(-1). Comparing the results of bones with and without marrow tested at low (0.002s(-1)) and high (0.05s(-1)) strain rates, presence of bone marrow did not have any significant effect on trabecular bone shear modulus and strength. In specimens without marrow, power relationships were used to define shear strength and modulus as dependent variables in terms of strain rate and apparent density as independent variables. The shear strength was proportional to the apparent density raised to the 1.02 power and to the strain rate raised to the 0.13 power. The shear modulus was proportional to the apparent density raised to the 1.08 power and to the strain rate raised to the 0.07 power. This study provides further insight into the mechanism of bone failure in trauma as well as failure at the interface between bone and implants as it relates to prediction of trabecular bone shear properties.     

Computed tomography in the diagnosis of exudative otitis media

Temporal bone computed tomography (CT) was used to examine 37 patients aged 2 to 55 years who had exudative otitis media; in 27 patients of them, a pathological process was bilateral. An analysis of 58 temporal bone CT scans identified the CT signs of chronic exudative otitis media. These included a partial or complete block of the osseous foramen of the auditory tube; impaired pneumatization of the tympanic cavity, mastoid process fenestrae, and antrum; pathological drawing-in of the tympanic membrane. The preservation of the auditory ossicles and the absence of destructive changes in the walls of the cavities of the middle ear were observed in most cases. Repeated temporal bone CT study was performed in 10 patients (14 temporal bones) in different periods (from 2 months to 3 years) after surgery. The results of tympanostomy were visually assessed. These included recovered pneumatization of middle ear cavities (7 temporal bones), a cicatricial process in the tympanic cavity (5 temporal bones), recurrence of the CT manifestations of exudative otitis media (2 temporal bones).     

Structural consequences of transcortical holes in long bones loaded in torsion

Finite element models were used to predict the structural consequences of transcortical holes through long bones loaded in torsion. Several parameters were investigated including hole size, anelastic behavior of the bone, cortical wall thickness, cortical wall symmetry, curvature along the bone's long axis and the axial length of the defect. Finite element model predictions of percent intact bone strength were compared to experimental data for sheep femora with transcortical drill holes loaded to failure in torsion. Hole size was expressed as hole diameter divided by the outer bone diameter. Linear finite element model predictions were in conservative agreement with the experimental data for large hole sizes. A transcortical hole with a diameter 50% of the outer bone diameter reduced the torsional strength by 60%. However, the linear models predict a 40% drop in strength for small holes whereas in vitro data suggest that small holes have no significant effect on strength. Models which represent non-linear anelastic behavior in bone over-predicted torsional strengths. Asymmetric cortical wall thickness and long bone bowing have minor effects, while the length of an elongated defect strongly influences the torsional strength. Strength reductions are greatest for bones with thin cortical walls.     

Pluripotent hemopoietic stem cells give rise to osteoclasts in vitro: effects of rGM-CSF

Studies involving bone marrow transplantation of osteopetrotic rodents have provided evidence for the lineage of the ostcoclast. Recent investigations have demonstrated that pluripotent hemopoietic stem cells (PHSC) isolated from the bone marrow of normal animals cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted into ia osteopetrotic rats. A criticism of these findings is that the microenvironment of the osteopetrotic bone and the bone marrow compartment may be unique in its ability to induce the differentiation of these stem cells into osteoclasts. To test this hypothesis, PHSC were co-cultured with fetal metatarsal bones from normal animals. PHSC were isolated from normal bone marrow using FITC-labelled monoclonal antibodies directed against rat Thy 1.1 and fluorescence-activated cell sorting. The PHSC or whole mononuclear bone marrow were co-cultured with 20-day fetal rat metatarsal rudiments. In some cultures, recombinant mouse granulocyte-macrophage colony-stimulating factor (rGM-CSF) (250 U per culture) was added in addition to the PHSC. After 7 days the fetal bones were prepared for light and electron microscopy and the number of osteoclasts generated in vitro was determined. The PHSC isolate generated as many osteoclasts as the whole mononuclear bone marrow. The addition of rGM-CSF did not enhance the generation of osteoclasts in either control bones or in bones cultured with PHSC. These results are equivalent to those reported in the osteopetrotic transplant system.     

Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone.

Data in the literature suggest that site-specific differences exist in the skeleton with respect to digestion of bone by osteoclasts. Therefore, we investigated whether bone resorption by calvarial osteoclasts (intramembranous bone) differs from resorption by long bone osteoclasts (endochondral bone). The involvement of two major classes of proteolytic enzymes, the cysteine proteinases (CPs) and matrix metalloproteinases (MMPs), was studied by analyzing the effects of selective low molecular weight inhibitors of these enzymes on bone resorption. Mouse tissue explants (calvariae and long bones) as well as rabbit osteoclasts, which had been isolated from both skeletal sites and subsequently seeded on bone slices, were cultured in the presence of inhibitors and resorption was analyzed. The activity of the CP cathepsins B and K and of MMPs was determined biochemically (CPs and MMPs) and enzyme histochemically (CPs) in explants and isolated osteoclasts. We show that osteoclastic resorption of calvarial bone depends on activity of both CPs and MMPs, whereas long bone resorption depends on CPs, but not on the activity of MMPs. Furthermore, significantly higher levels of cathepsin B and cathepsin K activities were expressed by long bone osteoclasts than by calvarial osteoclasts. Resorption of slices of bovine skull or cortical bone by osteoclasts isolated from long bones was not affected by MMP inhibitors, whereas resorption by calvarial osteoclasts was inhibited. Inhibition of CP activity affected the resorption by the two populations of osteoclasts in a similar way. We conclude that this is the first report to show that significant differences exist between osteoclasts of calvariae and long bones with respect to their bone resorbing activities. Resorption by calvarial osteoclasts depends on the activity of CPs and MMPs, whereas resorption by long bone osteoclasts depends primarily on the activity of CPs. We hypothesize that functionally different subpopulations of osteoclasts, such as those described here, originate from different sets of progenitors.     

Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation

Investigation of the bone and the bone marrow is critical in many research fields including basic bone biology, immunology, hematology, cancer metastasis, biomechanics, and stem cell biology. Despite the importance of the bone in healthy and pathologic states, however, it is a largely under-researched organ due to lack of specialized knowledge of bone dissection and bone marrow isolation. Mice are a common model organism to study effects on bone and bone marrow, necessitating a standardized and efficient method for long bone dissection and bone marrow isolation for processing of large experimental cohorts. We describe a straightforward dissection procedure for the removal of the femur and tibia that is suitable for downstream applications, including but not limited to histomorphologic analysis and strength testing. In addition, we outline a rapid procedure for isolation of bone marrow from the long bones via centrifugation with limited handling time, ideal for cell sorting, primary cell culture, or DNA, RNA, and protein extraction. The protocol is streamlined for rapid processing of samples to limit experimental error, and is standardized to minimize user-to-user variability.     

Diversity of cortical bone morphology in anuran amphibians

The cortical bones of mammals, birds, and reptiles are composed of a complex of woven bone and lamellar bone (fibrolamellar bone) organized into a variety of different patterns; however, it remains unclear whether amphibians possess similar structures. Importantly, to understand the evolutionary process of limb bones in tetrapods, it is necessary to compare the bone structure of amphibians (aquatic to terrestrial) with that of amniotes (mostly terrestrial). Therefore, this study compared the cortical bones in the long bones of several frog species before and after metamorphosis. Using micro-computed tomography (CT), we found that the cortical bones in the fibrolamellar bone of Xenopus tropicalis (Pipoidea superfamily) and Lithobates catesbeianus (Ranoidea superfamily) froglets are dense, whereas those of Ceratophrys cranwelli (Hyloidea superfamily) are porous. To clarify whether these features are common to their superfamily or sister group, four other frog species were examined. Histochemical analyses revealed porous cortical bones in C. ornata and Lepidobatrachus laevis (belonging to the same family, Ceratophryidae, as C. cranwelli). However, the cortical bones of Dryophytes japonicus (Hylidae, a sister group of Ceratophryidae in the Hyloidea superfamily), Microhyla okinavensis (Microhylidae, independent of the Hyloidea superfamily), and Pleurodeles waltl, a newt as an outgroup of anurans, are dense with no observed cavities. Our findings demonstrate that at least three members of the Ceratophryidae family have porous cortical bones similar to those of reptiles, birds, and mammals, suggesting that the process of fibrolamellar bone formation arose evolutionarily in amphibians and is conserved in the common ancestor of amniotes.     

Wall thickness of gas- and marrow-filled avian long bones: measurements on humeri, femora and tibiotarsi in crows (Corvus corone cornix) and magpies (Pica pica)

We studied how the ratio K of the internal to external diameter of gas- and marrow-filled avian long bones follows the biomechanical optima derived for tubular bones with minimum mass designed to fulfil various mechanical requirements. We evaluated radiographs of numerous humeri, femora and tibiotarsi in Corvus corone cornix and Pica pica. The K-values of the gas-filled humerus (K=0.78+/-0.03) and the marrow-filled femur (K=0.79+/-0.02) in Corvus are practically the same, while K of the marrow-filled tibiotarsus (K=0.71+/-0.04) is significantly smaller. The same is true for the gas-filled humerus (K=0.78+/-0.02) and the marrow-filled femur (K=0.77+/-0.02) and tibiotarsus (K=0.67+/-0.05) in Pica. K in Corvus is slightly larger than K in Pica, but the differences are statistically not significant. The standard deviation DeltaK of the tibiotarsi (DeltaK=0.04-0.05) is approximately two times as large as that of the humeri (DeltaK=0.02-0.03) and femora (DeltaK=0.02) in both species. Accepting the assumption of earlier authors that the ratio Q of the marrow to bone density is 0.5, our data show that the marrow-filled tibiotarsi of Corvus and Pica are optimized for stiffness, while the marrow-filled femora are far from any optimum. The relative wall thickness W=1-K of the gas-filled avian humeri studied is much larger than the theoretical optimum W*=1-K*=0.07, and thus these bones are thicker-walled than the optimal gas-filled tubular bone with minimum mass.     

Jaw and long bone marrow derived osteoclasts differ in shape and their response to bone and dentin

Increasing evidence suggests the existence of osteoclast diversity. Here we investigated whether precursors obtained from marrow of the mandibula or long bone could give rise to phenotypically different osteoclasts. Formation of multinucleated cells was assessed after culturing mouse marrow cells of the two bone types with macrophage colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL) for up to 10 days on plastic, bone or dentin. Two times more osteoclasts formed from long bone marrow cells on bone compared to dentin, whereas higher numbers of jaw osteoclasts formed on dentin. Resorption of dentin or bone was similar for osteoclasts formed from both types of precursors. In contrast to jaw marrow derived osteoclasts, long bone osteoclasts predominantly had a multi-compartmented shape, with at least two nuclei containing compartments per cell. Osteoclasts on bone contained two times more actin rings than osteoclasts on dentin, regardless of their precursor origin. However, the area per osteoclast covered by actin rings was similar (20%) for both substrates. This study suggests that marrow cells obtained from different bones give rise to different osteoclasts. The substrate on which the osteoclasts are generated plays a role in steering their formation rather than their resorption.     

Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury

Tissue repair often occurs in organs damaged by an inflammatory response. Inflammatory stimuli induce a rapid and massive release of inflammatory cells including neutrophils from the bone marrow. Recently, many studies suggested that bone marrow cells have the potential to differentiate into a variety of cell types. However, whether inflammatory stimuli induce release of bone marrow-derived progenitor cells (BMPCs), or how much impact the suppression of BMPCs has on the injured organ is not clear. Here we show that LPS, a component of Gram-negative bacterial cell walls, in the lung airways, induces a rapid mobilization of BMPCs into the circulation in mice. BMPCs accumulate within the inflammatory site and differentiate to become endothelial and epithelial cells. Moreover, the suppression of BMPCs by sublethal irradiation before intrapulmonary LPS leads to disruption of tissue structure and emphysema-like changes. Reconstitution of the bone marrow prevents these changes. These data suggest that BMPCs are important and required for lung repair after LPS-induced lung injury.     

Vitamin K therapy for cortical bone fragility caused by reduced mechanical loading in a child with hemiplegia

Fractures frequently occur at cortical bone sites in children with cerebral palsy, but there is no established therapy. We previously found that treatment with vitamins D and K increased cortical bone mass in children with severe physical disability, and have hypothesized that vitamin K could play a significant role in pediatric cortical bones under conditions with reduced mechanical loading. In the present case report, we treated a right hemiplegic ambulant eight-year-old boy with oral vitamin K (15 mg per day) for eight months. Cortical bone geometries at mid-diaphyseal sites in bilateral tibiae were evaluated before and after the treatment. The cross-sectional total, bone and marrow areas of non-hemiplegic tibia increased by 8.8%, 7.4% and 12.0%, respectively, while those of hemiplegic tibia changed by 9.0%, 14.9% and -3.4%, respectively. As a result, the polar moment of inertia, an indicator of the resistance to torsion forces, increased by 13.0% in the non-hemiplegic tibia and by 63.7% in the hemiplegic tibia. Vitamin K may restrict cortical bone fragility, caused by reduced mechanical loading, through its actions at the endosteal bone marrow interface. Further studies are needed to confirm these findings and to clarify the mechanisms involved.     

On the pathogenesis of osteogenesis imperfecta: some insights of the Utah paradigm of skeletal physiology

The pathogenesis of osteogenesis imperfecta (OI) baffled physiologists and physicians for over a century. Most past efforts to explain it depended heavily on cell and molecular biology and on changes in the material properties of affected bones (an old idea that OI patients could not make enough bone erred). To such views the still-evolving Utah paradigm of skeletal physiology can add a model for bone and bones that depends on errors in three genetically-determined features. The errors include, 1,2) elevated 'set points' of the strain-dependent thresholds that help to control how lamellar bone modeling and remodeling adapt bone strength, architecture and 'mass' to the voluntary loads on load-bearing bones; 3) and a reduced modeling-rate limit for the appositional rate of the lamellar bone formation drifts that can increase bone strength, outside bone diameters, cortical and trabecular thickness, and bone 'mass'. If only abnormalities #1,#2 occurred, that should limit the eventual strength, architecture and 'mass' of load-bearing bones, while if only #3 occurred that should prolong or delay how long it took to achieve the above limits, but without changing them. Equally, in driving from New York to Boston, stopping at New Haven would prevent reaching Boston no matter how rapidly one drove (a limited trip). But by not stopping one could reach Boston by driving very slowly (a prolonged but not a limited trip). This model concerns general features of bone and bones in OI that would need study and explanation at the tissue, cellular and molecular-biologic levels. Other places and people must discuss any devils in the details, as well as collagenous tissue, auditory, dental and other problems in OI, and the effects of treatment on the above features.     

Age and sex bias in the reconstruction of past population structures

Palaeodemographical studies are founded on the assumption that the sex and age distribution of the skeletal sample reflects the constitution of the original population. It is becoming increasingly clear, however, that the type and amount of information that may be derived from osteoarchaeological collections are related to the state of preservation of remains. This work proposes a new method to evaluate bone preservation, to identify age and sex biases in the preservation of human skeletal remains, and to assess whether differences in preservation patterns are more dependent on factors intrinsic or extrinsic to anatomical features of human bones. Three osteological collections and over 600 skeletons were observed. The state of preservation of human bones was assessed using three preservation indexes: the anatomical preservation index (API), the bone representation index (BRI), and the qualitative bone index (QBI). The results suggest that subadult skeletons are generally more poorly preserved and with bones less well-represented than adult skeletons. Among subadults, female and male skeletons have different patterns of preservation according to their age. This pattern of preservation depends on intrinsic anatomical properties of bones themselves, while external factors can only increase these differences in the state of preservation and representation of osseous remains. It is concluded from this that failure to recognize these differences may lead to misleading interpretations of paleodemography of past human populations.     

Remnant Woven Bone and Calcified Cartilage in Mouse Bone: Differences between Ages/Sex and Effects on Bone Strength

IntroductionMouse models are used frequently to study effects of bone diseases and genetic determinates of bone strength. Murine bones have an intracortical band of woven bone that is not present in human bones. This band is not obvious under brightfield imaging and not typically analyzed. Due to the band’s morphology and location it has been theorized to be remnant bone from early in life. Furthermore, lamellar and woven bone are well known to have differing mechanical strengths. The purpose of this study was to determine (i) if the band is from early life and (ii) if the woven bone or calcified cartilage contained within the band affect whole bone strength.

Woven Bone Origin Studies

In twelve to fourteen week old mice, doxycycline was used to label bone formed prior to 3 weeks old. Doxycycline labeling and woven bone patterns on contralateral femora matched well and encompassed an almost identical cross-sectional area. Also, we highlight for the first time in mice the presence of calcified cartilage exclusively within the band. However, calcified cartilage could not be identified on high resolution cone-beam microCT scans when examined visually or by thresholding methods.

Mechanical Strength Studies

Subsequently, three-point bending was used to analyze the effects of woven bone and calcified cartilage on whole bone mechanics in a cohort of male and female six and 13 week old Balb/C mice. Three-point bending outcomes were correlated with structural and compositional measures using multivariate linear regression. Woven bone composed a higher percent of young bones than older bones. However, calcified cartilage in older bones was twice that of younger bones, which was similar when normalized by area. Area and/or tissue mineral density accounted for >75% of variation for most strength outcomes. Percent calcified cartilage added significant predictive power to maximal force and bending stress. Calcified cartilage and woven bone could have more influence in genetic models where calcified cartilage percent is double our highest value.     

Effect of age on bone mineral density and micro architecture in the radius and tibia of horses: An Xtreme computed tomographic study

Background

The effect of age on the bone mineral density and microarchitecture of the equine radius and tibia was investigated. Fifty-six bones from 15 horses aged four to 21 years were used. There were nine geldings and six mares, and none of the horses had any disease influencing bone properties. Xtreme computed tomography was used to evaluate a 9-mm segment of the diaphysis and metaphysis of each bone. The following variables were determined: length of the bone, circumference and diameter in the frontal and sagittal planes in the middle of the bone.Diaphysis: total volume, bone volume, bone volume ratio, slice area, bone area, marrow area, cortical and marrow thickness, bone mineral density, polar moment of inertia of the cortex.Metaphysis: total area, bone area, cortical bone area, cortical thickness, bone mineral density, bone mineral density in the cortex, bone mineral density in the trabecular region, trabecular number, trabecular thickness, trabecular separation, polar moment of inertia of the metaphysis, polar moment of inertia of the cortex of the metaphysis.

Results

Bone density and microarchitecture were not affected by breed or gender. However, the microarchitecture varied with the age of the horse; the number of trabeculae decreased significantly and the distance between trabeculae increased significantly with increasing age. There were no significant differences between bones of the left and right limbs or between the radius and tibia.

Conclusion

The variables investigated did not differ between geldings and mares. However, there were age-related changes in the microstructure of the bones. Further experimental studies are necessary to determine whether these changes reduce bone strength. Age-related changes in the bones were seen and may explain the higher incidence of fractures and fissures in older horses.

     

Congenital osteopetrosis in white-tailed deer (Odocoileus virginianus)

Inferior brachygnathia in neonatal fawns occurred sporadically over a 10 yr period in a captive herd of white-tailed deer (Odocoileus virginianus) in southern Ontario. Two fawns submitted for necropsy had marked inferior brachygnathia, protruding tongues, and fractured long bones. Radiographs of the limbs revealed longitudinal striations of relatively translucent immature woven bone that caused loss of distinction between medullary cavities and cortices. Microscopically, there was failure of remodelling of the primary spongiosa and filling of the medulla by cone-shaped chondro-osseous cores. The findings supported a diagnosis of osteopetrosis, usually a hereditary disease characterized by absence of marrow cavities as a result of defective bone remodelling. Osteopetrosis has not been reported previously in deer.