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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 -
Tissue Engineering. Part B, Reviews Apr 2022Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone,... (Review)
Review
Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.
Topics: Bone Regeneration; Bone and Bones; Haversian System; Humans; Osteocytes; Osteogenesis
PubMed: 33487116
DOI: 10.1089/ten.TEB.2020.0322 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2022Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they...
Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they move erratically through the cortex and Type II osteons which show partial resorption and redeposition within the cement line of the osteon. Little is known about the biological significance of these variants. Prior studies suggested correlations with age, biomechanics, diet, and mineral homeostasis. No study has yet tested for osteon variant associations with static measures of bone remodeling. In this study, thin sections (n = 112) of the posterior femur representing a late English Medieval adult human osteological collection, subdivided by age, sex, and socio-economic status, were examined to determine whether remodeling indicators reconstructed from osteon parameters (area, diameter, area ratios) and densities differed between categories of presence or absence of Type II and drifting osteon variants. Of the 112 sections, 33 presented with Type II osteons, and 38 had drifting osteons. Sporadic statistically significant results were identified. Haversian canal:osteon area ratio differed (p = 0.017) with Type II osteon presence, Type II osteons were more prevalent in males than females (p = 0.048), and drifting osteons were associated with smaller osteon (p = 0.049) and Haversian canal area (p = 0.05). These results may be explained through some biological (sex) and social (status) processes such as a period of physiological recovery (e.g., following lactation, malnutrition). However, the general lack of consistent relationships between osteon variants and remodeling indicators suggests they occur as a result of natural variation.
Topics: Adult; Bone Remodeling; Bone and Bones; Cortical Bone; Female; Femur; Haversian System; Humans; Male
PubMed: 33890727
DOI: 10.1002/ar.24646 -
Micron (Oxford, England : 1993) Jan 2021Haversian systems result from bone remodeling, and show variation in size and shape among differing ages, body weights, mechanical environments, and species. While...
OBJECTIVES
Haversian systems result from bone remodeling, and show variation in size and shape among differing ages, body weights, mechanical environments, and species. While variables such as osteon circularity (On.Cr.) are generally studied in single transverse cross-sections, little is known about On.Cr. variation along an osteon's length, investigated here, in order to strengthen our understanding of bone microstructure.
MATERIALS AND METHODS
Up to 875 measurements of On.Cr. were generated for 41 osteonal segments from the proximal anterior diaphysis of femoral human cortical bone of three adult male samples (ages 46, 62, 74). We employed four hypotheses to investigate On.Cr. variability, in cross-section and longitudinally. H1: There is no difference in On.Cr. among osteons comprising single cross-sections, H2: There is no difference in On.Cr. among individuals when single cross-sections are compared, H3: There is no difference in On.Cr. among measurements taken from an osteon along the longitudinal axis, and H4: There is no discernable pattern in an osteon's deviation from circularity.
RESULTS
Quantitative analysis of single cross-sections revealed relatively consistent On.Cr. measurements within individual cross-sections and among individuals, supporting both, H1 and H2. Along individual osteonal segments, substantial degrees of dispersion from central tendencies were observed in 27 out of 41 analyzed osteons (despite relatively low overall standard deviations and interquartile ranges), leading to a rejection of H3. Qualitative characterization of morphological deviation from a "typical" circularity suggests a patterned deviation, leading also to a rejection of H4.
DISCUSSION
On.Cr. variation is discussed in the context of both, phenomena intrinsic to a given osteon (including repetitive, small perturbations at roughly 45 μm intervals), and extrinsic (including shared reversal sheaths, osteonal branching, transverse connections, and osteonal repathing). Interesting associations between On.Cr. and other characteristics of the local Haversian network emphasize the role of Haversian systems as integrated parts of a greater morphological complex.
Topics: Aged; Bone Remodeling; Cortical Bone; Haversian System; Humans; Male; Middle Aged; X-Ray Microtomography
PubMed: 33099207
DOI: 10.1016/j.micron.2020.102955 -
Advanced Healthcare Materials Jun 2015As one of the most important natural materials, cortical bone is a composite material comprising assemblies of tropocollagen molecules and nanoscale hydroxyapatite... (Review)
Review
As one of the most important natural materials, cortical bone is a composite material comprising assemblies of tropocollagen molecules and nanoscale hydroxyapatite mineral crystals, forming an extremely tough, yet lightweight, adaptive and multi-functional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are vital physiologically. Like many mineralized tissues, bone can resist deformation and fracture from the nature of its hierarchical structure, which spans molecular to macroscopic length-scales. In fact, bone derives its fracture resistance with a multitude of deformation and toughening mechanisms that are active at most of these dimensions. It is shown that bone's strength and ductility originate primarily at the scale of the nano to submicrometer structure of its mineralized collagen fibrils and fibers, whereas bone toughness is additionally generated at much larger, micro- to near-millimeter, scales from crack-tip shielding associated with interactions between the crack path and the microstructure. It is further shown how the effectiveness with which bone's structural features can resist fracture at small to large length-scales can become degraded by biological factors such as aging and disease, which affect such features as the collagen cross-linking environment, the homogeneity of mineralization, and the density of the osteonal structures.
Topics: Aging; Animals; Bone and Bones; Calcification, Physiologic; Collagen; Extracellular Matrix; Fractures, Bone; Humans
PubMed: 25865873
DOI: 10.1002/adhm.201500070 -
Journal of Forensic Sciences Jan 2022Histological analysis of bone tissue has been used to explore a variety of questions relating to age-at-death, habitual behaviors, health, and nutritional stress....
Histological analysis of bone tissue has been used to explore a variety of questions relating to age-at-death, habitual behaviors, health, and nutritional stress. Identification of intact and fragmentary osteons is of key interest to many researchers in these studies, yet the definitions of these features vary between researchers making cross-study comparisons problematic. Furthermore, histological variable definitions are often ambiguous or require subjective classifications by the observer. As a result, and as indicated by previous studies, observer error and misclassification of certain variables, namely intact and fragmentary osteons, can be significant. This study proposes new definitions for intact and fragmentary osteons that are designed to limit observer subjectivity and also explore efficacy of combining osteon types into one variable. A sample of 30 6th rib cross-sections from a modern forensic population was used to test the validity of the proposed definitions. Observations of intact osteon population density (OPD(I)) and fragmentary osteon population density (OPD(F)) were made by three observers for each cross-section. These observations were used to explore the interobserver error associated with the proposed definitions and determine if combining variables into one variable (OPD) mitigates persisting classification difficulties. Results indicate that the proposed definitions significantly reduce interobserver error and misclassification of intact and fragmentary osteons. However, the interobserver error associated with fragmentary osteons is still high. Evaluation of the variables independently indicates that combining variables has potential to reduce the predictive strength of an age estimation model and the ability to interpret age-related bone remodeling.
Topics: Bone Remodeling; Bone and Bones; Femur; Forensic Medicine; Haversian System
PubMed: 34821385
DOI: 10.1111/1556-4029.14949 -
Bioinspiration & Biomimetics Apr 2021Natural hard composites like human bone possess a combination of strength and toughness that exceeds that of their constituents and of many engineered composites. This...
Natural hard composites like human bone possess a combination of strength and toughness that exceeds that of their constituents and of many engineered composites. This augmentation is attributed to their complex hierarchical structure, spanning multiple length scales; in bone, characteristic dimensions range from nanoscale fibrils to microscale lamellae to mesoscale osteons and macroscale organs. The mechanical properties of bone have been studied, with the understanding that the isolated microstructure at micro- and nano-scales gives rise to superior strength compared to that of whole tissue, and the tissue possesses an amplified toughness relative to that of its nanoscale constituents. Nanoscale toughening mechanisms of bone are not adequately understood at sample dimensions that allow for isolating salient microstructural features, because of the challenge of performing fracture experiments on small-sized samples. We developed anthree-point bend experimental methodology that probes site-specific fracture behavior of micron-sized specimens of hard material. Using this, we quantify crack initiation and growth toughness of human trabecular bone with sharp fatigue pre-cracks and blunt notches. Our findings indicate that bone with fatigue cracks is two times tougher than that with blunt cracks.data-correlated electron microscopy videos reveal this behavior arises from crack-bridging by nanoscale fibril structure. The results reveal a transition between fibril-bridging (∼1m) and crack deflection/twist (∼500m) as a function of length-scale, and quantitatively demonstrate hierarchy-induced toughening in a complex material. This versatile approach enables quantifying the relationship between toughness and microstructure in various complex material systems and provides direct insight for designing biomimetic composites.
Topics: Biomimetics; Bone and Bones; Fractures, Bone; Humans; Stress, Mechanical
PubMed: 33470971
DOI: 10.1088/1748-3190/abdd9d -
Biofabrication Apr 2022The integration of three-dimensional (3D) bioprinted scaffold's structure and function for critical-size bone defect repair is of immense significance. Inspired by the...
The integration of three-dimensional (3D) bioprinted scaffold's structure and function for critical-size bone defect repair is of immense significance. Inspired by the basic component of innate cortical bone tissue-osteons, many studies focus on biomimetic strategy. However, the complexity of hierarchical microchannels in the osteon, the requirement of mechanical strength of bone, and the biological function of angiogenesis and osteogenesis remain challenges in the fabrication of osteon-mimetic scaffolds. Therefore, we successfully built mimetic scaffolds with vertically central medullary canals, peripheral Haversian canals, and transverse Volkmann canals structures simultaneously by 3D bioprinting technology using polycaprolactone and bioink loading with bone marrow mesenchymal stem cells and bone morphogenetic protein-4. Subsequently, endothelial progenitor cells were seeded into the canals to enhance angiogenesis. The porosity and compressive properties of bioprinted scaffolds could be well controlled by altering the structure and canal numbers of the scaffolds. The osteon-mimetic scaffolds showed satisfactory biocompatibility and promotion of angiogenesis and osteogenesisand prompted the new blood vessels and new bone formation. In summary, this study proposes a biomimetic strategy for fabricating structured and functionalized 3D bioprinted scaffolds for vascularized bone tissue regeneration.
Topics: Biomimetics; Bioprinting; Bone Regeneration; Haversian System; Osteogenesis; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 35417902
DOI: 10.1088/1758-5090/ac6700 -
Romanian Journal of Morphology and... 2023Otosclerosis is a bone condition affecting the stapes bone within the otic capsule, and its exact cause is still unknown. It is characterized by a lack of proper...
Otosclerosis is a bone condition affecting the stapes bone within the otic capsule, and its exact cause is still unknown. It is characterized by a lack of proper remodeling of newly formed vascular and woven bone, leading to the development of abnormal osteons and the formation of sclerotic bone. Bilateral otosclerosis is seen in 80% of patients and 60% of otosclerosis patients have a family history of the condition. The etiology of this disease is still unknown, there are lots of theories to explain it. The histopathological (HP) studies of otosclerosis showed that osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes were observed in the stapes footplate. The onset of the symptoms occurs by the early third decade of life, usually it doesn't start later. In otosclerosis, the energy exerted by sound at the level of the tympanic membrane is reduced in the inner ear due to the fixation and rigidity of the ossicular chain, leading to hearing loss, especially for low frequencies. The primary clinical symptom of otosclerosis is conductive hearing loss but it is important to note that sensorineural hearing loss and mixed hearing loss can also occur as secondary symptoms of the condition. Another symptom present in patients with otosclerosis is tinnitus. The paper carried out a retrospective study of 70 patients diagnosed with otosclerosis in the Department of Otorhinolaryngology of Emergency City Hospital, Timişoara, Romania, between January 2021 to December 2022. Tissue fragments were processed at Service of Pathology by standard Hematoxylin-Eosin staining. The HP diagnosis was completed using Masson's trichrome staining, Giemsa histochemical staining, and immunohistochemical (IHC) reactions with anti-cluster of differentiation (CD)20, anti-CD3, anti-CD4, anti-CD8, anti-CD34, and anti-CD31 antibodies. The microscopic examination showed a chronic diffuse inflammatory infiltrate that consisted predominantly of mature T-lymphocytes, immunohistochemically positive for CD3, CD4 and CD8. There were also present rare CD20-positive B-lymphocytes. Among the lymphocytes, relatively numerous mast cells were identified, highlighted histochemically by the Giemsa staining. They had numerous purple-violet intracytoplasmic granules. In the connective tissue support, a relatively rich vascular network was identified, consisting of hyperemic capillaries, highlighted immunohistochemically with anti-CD31 and anti-CD34 antibodies. Bone tissues trabeculae showed extensive areas of fibrosis. The collagen fibers were highlighted by Masson's trichrome staining, being stained in green, blue, or bluish green.
Topics: Humans; Otosclerosis; Retrospective Studies; Stapes; Hearing Loss, Conductive; Hearing Loss, Sensorineural; Deafness
PubMed: 37518876
DOI: 10.47162/RJME.64.2.09 -
Current Osteoporosis Reports Apr 2022Osteocytes are the conductors of bone adaptation and remodelling. Buried inside the calcified matrix, they sense mechanical cues and signal osteoclasts in case of low... (Review)
Review
PURPOSE OF REVIEW
Osteocytes are the conductors of bone adaptation and remodelling. Buried inside the calcified matrix, they sense mechanical cues and signal osteoclasts in case of low activity, and osteoblasts when stresses are high. How do osteocytes detect mechanical stress? What physical signal do they perceive? Finite element analysis is a useful tool to address these questions as it allows calculating stresses, strains and fluid flow where they cannot be measured. The purpose of this review is to evaluate the capabilities and challenges of finite element models of bone, in particular the osteocytes and load-induced activation mechanisms.
RECENT FINDINGS
High-resolution imaging and increased computational power allow ever more detailed modelling of osteocytes, either in isolation or embedded within the mineralised matrix. Over the years, homogeneous models of bone and osteocytes got replaced by heterogeneous and microstructural models, including, e.g. the lacuno-canalicular network and the cytoskeleton. The lacuno-canalicular network induces strain amplifications and the osteocyte protrusions seem to be stimulated much more than the cell body, both by strain and fluid flow. More realistic cell geometries, like minute constrictions of the canaliculi, increase this effect. Microstructural osteocyte models describe the transduction of external stimuli to the nucleus. Supracellular multiscale models (e.g. of a tunnelling osteon) allow to study differential loading of osteocytes and to distinguish between strain and fluid flow as the pivotal stimulatory cue. In the future, the finite element models may be enhanced by including chemical transport and intercellular communication between osteocytes, osteoclasts and osteoblasts.
Topics: Bone and Bones; Finite Element Analysis; Humans; Mechanotransduction, Cellular; Osteocytes; Stress, Mechanical
PubMed: 35298773
DOI: 10.1007/s11914-022-00728-9