Shape Of Long Bones Research Articles

How can research on modern and fossil bones help us build more resistant columns?

Bone is an economical material. Indeed, as moving a heavy skeleton is energetically costly, the vertebrate skeleton is adapted to maximise resistance to the stresses imposed with a minimum amount of material, so that bone tissue is deposited where it is needed. Using bone as a source of inspiration should therefore reduce the manufacturing cost (both financial and ecological) and increase the strength (and lifespan) of bioinspired (BI) structures. This study proposes to investigate which adaptive features of the outer shape and inner structure of bone, related to compressive strength, could be used to build BI support structures. To do so, we explain the choice of the bones to be analysed and present the results of the biomechanical analyses (finite element analysis) carried out on virtual models built from the structures of the different bone models and of the mechanical tests carried out on 3D-printed versions of these models. The compressive strength of these direct bone BI columns was compared with each other, and with those of a conventional filled cylindrical column, and of a cylindrical column whose internal structure is BI from the radius of the white rhinoceros. The results of our comparative analyses highlight that the shape of long bones is less effective than a cylinder in resisting compression but underline the relevance in designing BI cylindrical columns with heterogeneous structures inspired by the radius of the white rhinoceros and the tibia of the Asian elephant, and raise the interest in studying the fossil record using the radius of the giant rhinocerotoid Paraceratherium.

La maladie des exostoses multiples

Hereditary multiple exostosis (HEM) is one of the most common hereditary diseases. It is characterized by the proliferation of bone protuberances, especially located in the metaphysis of long bones. The disease phenotype may also associate abnormalities in the shape and length of long bones, such as the typical “Bessel Hagen” deformity. Clinically, the main complaint of patients remains pain, but the psychological and social consequences should not be minimized. The rare complication (2 to 5% of cases) but the most feared is the transformation into chondrosarcoma, which motivates regular clinical and radiological monitoring of these patients. This follow-up, although essential, remains poorly defined, including at a minimum, an annual clinical examination and radiological follow-up based on the symptoms described by the patients. The treatment remains mainly surgical, with patients being most often multi-operated during the course of the disease. Medical treatment remains secondary. In recent years, progress has been made in understanding the pathophysiology of this disease, particularly with the discovery of the mutation of EXT genes, found in 80% of HME cases. These tumor suppressor genes encode proteins that act in the synthesis of heparan sulfates (HS). The decrease in the amount of HS leads to changes in certain metabolic pathways, which explains the development of ectopic growth plaques, which are the cause of bone exostosis, but also the poor longitudinal growth of long bones. The greater knowledge of the mechanisms underlying this disease makes it possible to consider potential therapeutic targets.

Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts

SummaryWe identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long bones. hiPSCs from CMD patients with an in-frame deletion of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast differentiation than control hiPSCs. To exclude differentiation effects due to genetic variability, we generated isogenic hiPSCs, which have identical genetic background except for the ANKH mutation. Isogenic hiPSCs with ANKH mutations formed fewer osteoclasts, resorbed less bone, expressed lower levels of osteoclast marker genes, and showed decreased protein levels of ANKH and vacuolar proton pump v-ATP6v0d2. This proof-of-concept study demonstrates that efficient and reproducible differentiation of isogenic hiPSCs into osteoclasts is possible and a promising tool for investigating mechanisms of CMD or other osteoclast-related disorders.

Swimming and running: a study of the convergence in long bone morphology among semi-aquatic mustelids (Carnivora: Mustelidae)

The shape of long bones is linked to a species' ecology and is thought to reflect the constraints imposed by locomo-tion. The evolution of the shape of the long bones in semi-aquatic mustelids has likely been shaped by the divergent mechanical properties of both water and land. Adaptation to a semi-aquatic lifestyle occurred independently in otters (Lutrinae) and minks (Mustelinae). Here we test the idea that these similar locomotor constraints led to morphological convergence between minks and otters, and between European and American minks. We use 3D geometric morphometrics to quantify shape differences in the humerus, radius, ulna, femur, tibia and fibula of ten species of mustelids belonging to the Lutrinae and Mustelinae subfamilies. Our results show convergence in all bones between the European and American minks, but this convergence is significant only for the humerus. We suggest that this strong convergence in humeral shape between the two minks results from functional demands on the forelimb as it produces most of the thrust when swimming in minks. The American minks show a slight but nonsignificant convergence with the Lutrinae for the shape of the ulna, femur and tibia. The sea otter (Enhydra lutris) shows an ulnar and radial shape that diverges from that observed in the other Lutrinae, possibly due to the strong manipulative abilities and unique locomotor mode of this species. In contrast to our initial hypothesis, bone shape in minks does not converge significantly with that of otters. Otters show a large variety of shapes suggesting that a semi-aquatic lifestyle can comprise a wide array of locomotor behaviours.

Scaling effect on the mid-diaphysis properties of long bones-the case of the Cervidae (deer).

How skeletal elements scale to size is a fundamental question in biology. While the external shape of long bones was intensively studied, an important component of their organization is also found in their less accessible inner structure. Here, we studied mid-diaphyseal properties of limb long bones, characterizing notably the thickness of their cortices (bone walls), in order to test whether body size directly influences bone inner organization. Previous examinations of scaling in long bones used broad samplings to encompass a wide range of body sizes. To account for the effect of confounding factors related to different lifestyles, we focused our comprehensive sampling on a mammalian clade that comprises various body sizes but a relatively uniform lifestyle, the Cervidae. Positive allometry was found in femoral cross-sectional shape, indicating greater directional bending rigidity in large-sized taxa. None of the compactness parameters scaled allometrically in any of their bones. The cortices of sampled zeugopodial bones (tibia and radius) were found as significantly thicker than those of stylopodial bones (femur and humerus). Furthermore, while the mean relative cortical thickness values for both stylopodial and zeugopodial bones are close to mass-saving optima, the variance for the stylopodial bones is significantly lower. This suggests that mass saving is less intensively selected in zeugopodial bones. Finally, the long-legged Elk (Alces) and the short-legged dwarf Cretan deer (Candiacervus) featured rather thin and thick cortices, respectively, suggesting that the acquisition of a different limb proportion is accompanied by a modification of the relative mid-diaphyseal cortical thickness.

Phenotypic Analysis of Long Bones in Pannexin 3 Knockout Mice Using a Geometric Morphometric Approach

Pannexin 3 (Panx3) is a channel‐forming glycoprotein that is expressed in skin, mammary gland and skeletal tissues. In vitro studies have shown that Panx3 is induced at the growth plate where it is thought to promote cell differentiation, a key role in bone formation. However, whether or not the ablation of Panx3 in mice causes phenotypic anomalies is unknown.The study objective is to analyze the phenotype of long bones in a new Panx3 knockout (KO) mouse to assess the role of Panx3 in bone formation.Ten KO and 10 wild‐type (WT) adult mice were scanned using high resolution in vivo micro‐CT. Each long bone studied was digitized using homologous landmarks. Data analysis using geometric morphometrics (multivariate statistical methods) allowed for a quantitative comparison of shape, size and variation of long bones between KO and WT mice.KO mice demonstrated distinct long bone shape differences that were greatest at the joint surfaces. As well, long bones in KO mice were 5% smaller. A significant portion of the shape difference (20%) can be attributed to the size component of shape. KO mice demonstrated greater shape variation that also appeared to be driven by different patterns of growth.Our findings suggest that Panx3 affects long bone shape through its effect on size. Importantly, KO mice appear to have altered and less predictable patterns of long bone growth. Thus, Panx3 may have a role in maintaining optimum bone growth.

Induced Pluripotent Stem Cell Reprogramming by Integration-Free Sendai Virus Vectors from Peripheral Blood of Patients with Craniometaphyseal Dysplasia

Studies of rare genetic bone disorders are often limited due to unavailability of tissue specimens and the lack of animal models fully replicating phenotypic features. Craniometaphyseal dysplasia (CMD) is a rare monogenic disorder characterized by hyperostosis of craniofacial bones concurrent with abnormal shape of long bones. Mutations for autosomal dominant CMD have been identified in the ANK gene (ANKH). Here we describe a simple and efficient method to reprogram adherent cells cultured from peripheral blood to human induced pluripotent stem cells (hiPSCs) from eight CMD patients and five healthy controls. Peripheral blood mononuclear cells (PBMCs) were separated from 5-7 mL of whole blood by Ficoll gradient, expanded in the presence of cytokines and transduced with Sendai virus (SeV) vectors encoding OCT3/4, SOX2, KLF4, and c-MYC. SeV vector, a cytoplasmic RNA vector, is lost from host cells after propagation for 10-13 passages. These hiPSCs express stem cell markers, have normal karyotypes, and are capable of forming embryoid bodies in vitro as well as teratomas in vivo. Further differentiation of these patient-specific iPSCs into osteoblasts and osteoclasts can provide a useful tool to study the effects CMD mutations on bone, and this approach can be applied for disease modeling of other rare genetic musculoskeletal disorders.

Age-related changes and secular trends in hand bone size

The aim of the present study was to evaluate age- and sex-related changes in the size and shape of long hand bones in a large Chuvashian cohort using cross-sectional and longitudinal study designs. The data were gathered in 1994 (557 individuals) and 2002 (513 individuals). The latter sample included 260 individuals that were studied only during the second expedition, and 253 individuals who were previously investigated in 1994. Statistical analyses included a maximum likelihood-based model-fitting technique and a t-test comparison. We found evidence for secular trend of hand bone size in both males and females within the Chuvashian population. In males, the length and total area of the long hand bones were greater in younger individuals, but mid-shaft bone width remained almost the same in individuals born at different periods of the last century. In females, the length of the hand bones and total bone area remained unchanged in women born after 1937. However, bone mid-shaft width gradually decreased in women born after 1940. Therefore, we argue that, at least within the Chuvashian population, there is a secular trend towards a more gracile appendicular skeleton in both males and females.

The variation of the cross-sectional shape in the long bones of birds and mammals

The transverse and sagittal diameters of the long bones were measured in a sample of 53 species of eutherian mammals and 36 species of birds. The scaling of the transverse and sagittal diameters of each bone to body mass was calculated. For each bone the ratio of sagittal/transverse diameter was calculated, as an expression of the cross-sectional shape of the bones. The distributions of the ratios were not significantly different from normality in all the avian bones and in the mammalian femur and tibia. In most cases, the mean of the distribution was significantly different from 1 (circular shape). The analysis shows that changes in the ratio can be caused by selective factors, considering the correlation predicted between the breaking moments and the radii, but at the same time the cross-sectional shape of mammalian and avian long bones may have a phylogenetic basis. Finally, the previous assumption of relationship between bone curvature and stress predictability, is also discussed.

Assessment of long bone flexural properties from bone densitometry

While bone densitometry is the accepted non-invasive method of quantifying bone mineral content in bones, its assessment of bone structural properties is less well understood. The objective of our current work is to compare cross-section shape or areal properties of long bones computed from densitometry data with cross-section flexural properties obtained from surface strain measurements.

Fetal Imaging in the Skeletal Dysplasias

Second-trimester diagnosis of fetal skeletal dysplasia is becoming increasingly common. By careful examination of the fetus for skeletal mineralization, shape and size of long bones and cranium, and abnormalities of other organ systems, a definitive diagnosis can often be achieved by ultrasound. Fetal radiography is very helpful in giving more information about bone shape and mineralization as well as in confirming the diagnosis. Subsequent obstetric management should be dictated by the natural history of the disease, the parents' wishes, and the gestational age at diagnosis. Because many of these disorders have a high recurrence risk, genetic counseling and follow-up are an important part of the management of these patients.

Three recessive genes for congenital osteopetrosis in Norway rat.

In the rat, the autosomal recessive toothless (t1) mutation exhibits an acute form of osteopetrosis. This gene is not an allele of either ia or op that causes respectively, a transitory and acute form of the disease. Comparative radiographic study of t1/t1 and op/op mutants reveals some differences in respect to the size and shape of long bones. In contrast to op/op mutants, homozygous t1/t1 animals failed to respond to either parabiosis or bone marrow transplants.

Bone remodeling and piezoelectricity — II

The piezoelectric model for bone remodeling presented in the companion paper is investigated in more detail. The predictions of the model are compared with experimental and clinical observation relating to: 1. 1. The shape of normal long bones. 2. 2. Bone disuse atrophy. 3. 3. Shape of the metaphysical part of long bones during growth. 4. 4. Growth correction of angular deformity in fractured long bones. The predictions of the model appear to be reasonable.