-
Bone Aug 2023Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth....
Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth. Resulting impairment of skeletal modeling, remodeling, and growth compromises widening of medullary spaces, formation of the skull, and expansion of cranial foramina. Thus, myelophthisic anemia, raised intracranial pressure, and cranial nerve palsies complicate OPT when severe. Osteopetrotic bones fracture due to misshaping, failure of remodeling to weave the collagenous matrix of cortical osteons and trabeculae, persistence of mineralized growth plate cartilage, "hardening" of hydroxyapatite crystals, and delayed healing of skeletal microcracks. Teeth may fail to erupt. Now it is widely appreciated that OPT is caused by germline loss-of-function mutation(s) usually of genes involved in osteoclast function, but especially rarely of genes necessary for osteoclast formation. Additionally, however, in 2003 we published a case report demonstrating that prolonged excessive dosing during childhood of the antiresorptive aminobisphosphonate pamidronate can sufficiently block osteoclast and chondroclast activity to recapitulate the skeletal features of OPT. Herein, we include further evidence of drug-induced OPT by illustrating osteopetrotic skeletal changes from repeated administration of high doses of the aminobisphosphonate zoledronic acid (zoledronate) given to children with osteogenesis imperfecta.
Topics: Child; Humans; Osteopetrosis; Osteoclasts; Zoledronic Acid; Fractures, Bone; Skull
PubMed: 37172883
DOI: 10.1016/j.bone.2023.116788 -
Acta Biomaterialia Aug 2023Velar bone is the material that fills the horncore of bighorn sheep rams. The architectural dimensions of velar bone are orders of magnitude larger than trabecular bone,...
Velar bone is the material that fills the horncore of bighorn sheep rams. The architectural dimensions of velar bone are orders of magnitude larger than trabecular bone, and velae are more sail-like compared to strut-like trabeculae. Velar bone is important for energy absorption and reduction of brain cavity accelerations during high energy head impacts, but velar bone material properties were previously unknown. It was hypothesized that velar bone tissue would have properties that are beneficial for increased energy absorption at the material level. Solid velar bone beams were tested using dynamic mechanical analysis and three-point bending to quantify mechanical properties. Additionally, the porosity, osteon population density, and mineral content of the solid velar sails were quantified. The velar bone damping factor (∼0.03 - 0.06) and modulus of toughness (3.9 ± 0.4 MJ/m) were lower than other mammalian cortical bone tissues. The solid bony sails have a bending modulus (8.6 ± 0.5 GPa) that lies within the range of bending moduli values previously reported for individual trabecular struts and cortical bone tissue. The solid velar bone sails had porosity (6.7 ± 0.9 %) and bone mineral content (66 ± 1 %) in the range of cortical bone values. Interestingly, velar sails contained osteons, which are rarely found in trabecular struts. The velar bone osteon population density (5.8 ± 0.9 osteons/mm) is in the low end of the range of values reported for cortical bone in other mammals. STATEMENT OF SIGNIFICANCE: Bighorn sheep rams sustain high energy head impacts during intraspecific combat without overt signs of brain injury. Previous studies have shown that the bony horncore plays a critical role in energy absorption and reduction of brain cavity accelerations post impact, which has implications for concussion prevention in humans. However, the material properties of the horncore velar bone were previously unknown. This study quantified the material properties and structure-property relationships of the horncore velar bone at the tissue level. Results from this study will improve our understanding of how bighorn sheep mitigate brain injury during head-to-head impacts and may inspire the design of novel materials for energy absorption applications (i.e., helmets materials that reduce concussion occurrence in humans).
Topics: Humans; Animals; Male; Sheep; Sheep, Bighorn; Skull; Bone Density; Porosity; Brain Injuries
PubMed: 37164299
DOI: 10.1016/j.actbio.2023.05.013 -
Acta Biomaterialia Sep 2023The development of treatment strategies for skeletal diseases relies on the understanding of bone mechanical properties in relation to its structure at different length...
The development of treatment strategies for skeletal diseases relies on the understanding of bone mechanical properties in relation to its structure at different length scales. At the microscale, indention techniques can be used to evaluate the elastic, plastic, and fracture behaviour of bone tissue. Here, we combined in situ high-resolution SRµCT indentation testing and digital volume correlation to elucidate the anisotropic crack propagation, deformation, and fracture of ovine cortical bone under Berkovich and spherical tips. Independently of the indenter type we observed significant dependence of the crack development due to the anisotropy ahead of the tip, with lower strains and smaller crack systems developing in samples indented in the transverse material direction, where the fibrillar bone ultrastructure is largely aligned perpendicular to the indentation direction. Such alignment allows to accommodate the strain energy, inhibiting crack propagation. Higher tensile hoop strains generally correlated with regions that display significant cracking radial to the indenter, indicating a predominant Mode I fracture. This was confirmed by the three-dimensional analysis of crack opening displacements and stress intensity factors along the crack front obtained for the first time from full displacement fields in bone tissue. The X-ray beam significantly influenced the relaxation behaviour independent of the tip. Raman analyses did not show significant changes in specimen composition after irradiation compared to non-irradiated tissue, suggesting an embrittlement process that may be linked to damage of the non-fibrillar organic matrix. This study highlights the importance of three-dimensional investigation of bone deformation and fracture behaviour to explore the mechanisms of bone failure in relation to structural changes due to ageing or disease. STATEMENT OF SIGNIFICANCE: Characterising the three-dimensional deformation and fracture behaviour of bone remains essential to decipher the interplay between structure, function, and composition with the aim to improve fracture prevention strategies. The experimental methodology presented here, combining high-resolution imaging, indentation testing and digital volume correlation, allows us to quantify the local deformation, crack propagation, and fracture modes of cortical bone tissue. Our results highlight the anisotropic behaviour of osteonal bone and the complex crack propagation patterns and fracture modes initiating by the intricate stress states beneath the indenter tip. This is of wide interest not only for the understanding of bone fracture but also to understand other architectured (bio)structures providing an effective way to quantify their toughening mechanisms in relation to their main mechanical function.
Topics: Sheep; Animals; Synchrotrons; Anisotropy; Bone and Bones; Cortical Bone; Fractures, Bone; Stress, Mechanical
PubMed: 37127075
DOI: 10.1016/j.actbio.2023.04.038 -
Computer Methods in Biomechanics and... 2024The bone lacunar-canalicular system (LCS) is a unique complex 3D microscopic tubular network structure within the osteon that contains interstitial fluid flow to ensure...
The bone lacunar-canalicular system (LCS) is a unique complex 3D microscopic tubular network structure within the osteon that contains interstitial fluid flow to ensure the efficient transport of signaling molecules, nutrients, and wastes to guarantee the normal physiological activities of bone tissue. The mass transfer laws in the LCS under microgravity and hypergravity are still unclear. In this paper, a multi-scale 3D osteon model was established to mimic the cortical osteon, and a finite element method was used to numerically analyze the mass transfer in the LCS under hypergravity, normal gravity and microgravity and combined with high-intensity exercise conditions. It was shown that hypergravity promoted mass transfer in the LCS to the deep lacunae, and the number of particles in lacunae increased more significantly from normal gravity to hypergravity the further away from the Haversian canal. The microgravity environment inhibited particles transport in the LCS to deep lacunae. Under normal gravity and microgravity, the number of particles in lacunae increased greatly when doing high-intensity exercise compared to stationary standing. This paper presents the first simulation of mass transfer within the LCS with different gravity fields combined with high-intensity exercise using the finite element method. The research suggested that hypergravity can greatly promote mass transfer in the LCS to deep lacunae, and microgravity strongly inhibited this mass transfer; high-intensity exercise increased the mass transfer rate in the LCS. This study provided a new strategy to combat and treat microgravity-induced osteoporosis.
Topics: Hypergravity; Weightlessness; Bone and Bones; Computer Simulation
PubMed: 36912751
DOI: 10.1080/10255842.2023.2187738 -
Journal of Advanced Research Dec 2023The bone ingrowth depth in the porous scaffolds is greatly affected by the structural design, notably the pore size, pore geometry, and the pore distribution. To enhance...
INTRODUCTION
The bone ingrowth depth in the porous scaffolds is greatly affected by the structural design, notably the pore size, pore geometry, and the pore distribution. To enhance the bone regeneration capability of scaffolds, the bionic design can be regarded as a potential solution.
OBJECTIVES
We proposed a Haversian system-like gradient structure based on the triply periodic minimal surface architectures with pore size varying from the edge to the center. And its effects in promoting bone regeneration were evaluated in the study.
METHODS
The gradient scaffold was designed using the triply periodic minimal surface architectures. The mechanical properties were analyzed by the finite element simulation and confirmed using the universal machine. The fluid characteristics were calculated by the computational fluid dynamics analysis. The bone regeneration process was simulated using a in silico computational model containing the main biological, physical, and chemical variation during the bone growth process. Finally, the in vitro and in vivo studies were carried out to verify the actual osteogenic effect.
RESULTS
Compared to the uniform scaffold, the biomimetic gradient scaffold demonstrated better performance in stress conduction and reduced stress shielding effects. The fluid features were appropriate for cell migration and flow diffusion, and the permeability was in the same order of magnitude with the natural bone. The bone ingrowth simulation exhibited improved angiogenesis and bone regeneration. Higher expression of the osteogenesis-related genes, higher alkaline phosphatase activity, and increased mineralization could be observed on the gradient scaffold in the in vitro study. The 12-week in vivo study proved that the gradient scaffold had deeper bone inserting depth and a more stable bone-scaffold interface.
CONCLUSION
The Haversian system-like gradient structure can effectively promote the bone regeneration. This structural design can be used as a new solution for the clinical application of prosthesis design.
Topics: Tissue Scaffolds; Porosity; Haversian System; Osteogenesis; Bone Regeneration
PubMed: 36632888
DOI: 10.1016/j.jare.2023.01.004 -
International Journal of Legal Medicine Jan 2024Timing bone fractures is one of the main tasks of a forensic anthropologist, but still an uncertain diagnostic. In the literature, there are many macroscopic methods to...
Timing bone fractures is one of the main tasks of a forensic anthropologist, but still an uncertain diagnostic. In the literature, there are many macroscopic methods to distinguish perimortem from postmortem fractures, based on the distinct structural and mechanical properties of fresh and dry bones. However, this differentiation is still challenging, in particular when the bones are fragmented or still exhibit fresh properties. Although histologic analysis is often used as a complementary diagnostic tool in forensic pathology, its application in the evaluation of bone fractures is uncommon. The aim of this study was to investigate whether fractures of fresh bones reveal a distinct microcracking pattern compared to fractures of dry bones, in order to optimise the fracture timing. To this purpose, we histologically analysed perimortem and postmortem fractures in human humeri. The fresh bones were retrieved from traumatic autopsy cases, and the dry bones from donors which were experimentally fractured. Our results showed that the highest density and length of microcracks (MCKs) were found in the interstitial area of dry fractured bones, which may be considered a marker of postmortem damage. In fresh fractured bones, we generally observed a lower density of MCKs, but a higher proportion of osteonal MCKs, which may be considered a marker of perimortem trauma. In summary, the results of our exploratory study suggest that changes in intrinsic bone factors (mineral/organic components) result in a different microcracking pattern that can be used in fracture timing.
Topics: Humans; Fractures, Bone; Autopsy; Forensic Pathology; Haversian System; Humerus; Postmortem Changes
PubMed: 36066767
DOI: 10.1007/s00414-022-02875-1