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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 -
Journal of Functional Biomaterials Jul 2023One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and...
One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and increase efficiency. Hydroxyapatite (HA), the main inorganic component of bones and teeth, has high biocompatibility but is weak and brittle material. Cortical bone is composed of 70% calcium phosphate (CaP) and 30% collagen and forms a complex hierarchical structure with anisotropic and lamellar microstructure (osteons) which makes bone a light, strong, tough, and durable material that can support large loads. However, imitation of concentric lamellar structure of osteons is difficult to achieve in fabrication. Nacre from mollusk shells with layered structures has now become the archetype of the natural "model" for bio-inspired materials. Incorporating a nacre-like layered structure into bone implants can enhance their mechanical strength, toughness, and durability, reducing the risk of implant catastrophic failure or fracture. The layered structure of nacre-like HA/polymer composites possess high strength, toughness, and tunable stiffness which matches that of bone. The nacre-like HA/polymer composites should also possess excellent biocompatibility and bioactivity which facilitate the bonding of the implant with the surrounding bone, leading to improved implant stability and long-term success. To achieve this, a bi-directional freeze-casting technique was used to produce elongated lamellar HA were further densified and infiltrated with polymer to produce nacre-like HA/polymer composites with high strength and fracture toughness. Mechanical characterization shows that increasing the ceramic fractions in the composite increases the density of the mineral bridges, resulting in higher flexural and compressive strength. The nacre-like HA/(methyl methacrylate (MMA) + 5 wt.% acrylic acid (AA)) composites with a ceramic fraction of 80 vol.% showed a flexural strength of 158 ± 7.02 MPa and a Young's modulus of 24 ± 4.34 GPa, compared with 130 ± 5.82 MPa and 19.75 ± 2.38 GPa, in the composite of HA/PMMA, due to the higher strength of the polymer and the interface of the composite. The fracture toughness in the composition of 5 wt.% PAA to PMMA improves from 3.023 ± 0.98 MPa·m to 5.27 ± 1.033 MPa·m by increasing the ceramic fraction from 70 vol.% to 80 vol.%, respectively.
PubMed: 37623638
DOI: 10.3390/jfb14080393 -
American Journal of Biological... Oct 2023In modern bone biology, the term "remodeling" generally refers to internal bone turnover that creates secondary osteons. However, it is also widely used by skeletal... (Review)
Review
OBJECTIVES
In modern bone biology, the term "remodeling" generally refers to internal bone turnover that creates secondary osteons. However, it is also widely used by skeletal biologists, including biological anthropologists as a catch-all term to refer to different skeletal changes. In this review, we investigated how "remodeling" is used across topics on skeletal biology in biological anthropology to demonstrate potential problems with such pervasive use of a generalized term.
METHODS
Using PubMed and Google Scholar, we selected and reviewed 205 articles that use the term remodeling to describe skeletal processes and have anthropological implications. Nine edited volumes were also reviewed as examples of collaborative work by different experts to demonstrate the diverse and extensive use of the term remodeling.
RESULTS
Four general meanings of bone "remodeling" were identified, namely, internal turnover, functional adaptation, fracture repair, and growth remodeling. Additionally, remodeling is also used to refer to a broad array of pathological skeletal changes.
DISCUSSION
Although we initially identified four general meanings of bone remodeling, they are not mutually exclusive and often occur in combination. The term "remodeling" has become an extensively used catch-all term to refer to different processes and outcomes of skeletal changes, which inevitably lead to misunderstanding and a loss of information. Such ambiguity and confusion are potentially problematic as the field of biological anthropology becomes increasingly multidisciplinary. Therefore, we advocate for precise, context-specific definitions and explanations of bone remodeling as it continues to be used across disciplines within and beyond biological anthropology.
Topics: Anthropology; Bone and Bones; Bone Remodeling
PubMed: 37515465
DOI: 10.1002/ajpa.24825 -
Acta Biomaterialia Sep 2023Osteodentin is a dominant mineralized collagenous tissue in the teeth of many fishes, with structural and histological characteristics resembling those of bone....
Osteodentin is a dominant mineralized collagenous tissue in the teeth of many fishes, with structural and histological characteristics resembling those of bone. Osteodentin, like bone, comprises osteons as basic structural building blocks, however, it lacks the osteocytes and the lacuno-canalicular network (LCN), which are known to play critical roles in controlling the mineralization of the collagenous matrix in bone. Although numerous vascular canals exist in osteodentin, their role in tooth maturation and the matrix mineralization process remain poorly understood. Here, high resolution micro-computed tomography (micro-CT) and focused ion beam-scanning electron microscopy (FIB-SEM) were used to obtain 3D structural information of osteodentin in shark teeth at multiple scales. We observed a complex 3D network of primary canals with a diameter ranging from ∼10 µm to ∼120 µm, where the canals are surrounded by osteon-like concentric layers of lamellae, with 'interosteonal' tissue intervening between neighboring osteons. In addition, numerous hierarchically branched secondary canals extended radially from the primary canals into the interosteonal tissue, decreasing in diameter from ∼10 µm to hundreds of nanometers. Interestingly, the mineralization degree increases from the periphery of primary canals into the interosteonal tissue, suggesting that mineralization begins in the interosteonal tissue. Correspondingly, the hardness and elastic modulus of the interosteonal tissue are higher than those of the osteonal tissue. These results demonstrate that the 3D hierarchical canal network is positioned to play a critical role in controlling the gradient mineralization of osteodentin, also providing valuable insight into the formation of mineralized collagenous tissue without osteocytes and LCN. STATEMENT OF SIGNIFICANCE: Bone is a composite material with versatile mechanical properties. Osteocytes and their lacuno-canalicular network (LCN) are known to play critical roles during formation of human bone. However, the bone and osteodentin of many fishes, although lacking osteocytes and LCN, exhibit similar osteon-like structure and mechanical functions. Here, using various high resolution 3D characterization techniques, we reveal that the 3D network of primary canals and numerous hierarchically branched secondary canals correlate with the mineralization gradient and micromechanical properties of osteonal and interosteonal tissues of shark tooth osteodentin. This work significantly improves our understanding of the construction of bone-like mineralized tissue without osteocytes and LCN, and provides inspirations for the fabrication of functional materials with hierarchical structure.
Topics: Humans; Animals; X-Ray Microtomography; Bone and Bones; Osteocytes; Haversian System; Sharks
PubMed: 37451657
DOI: 10.1016/j.actbio.2023.07.007 -
PloS One 2024The histological, or microscopic, appearance of bone tissue has long been studied to identify species-specific traits. There are several known histological...
The histological, or microscopic, appearance of bone tissue has long been studied to identify species-specific traits. There are several known histological characteristics to discriminate animal bone from human, but currently no histological characteristic that has been consistently identified in human bone exclusive to other mammals. The drifting osteon is a rare morphotype found in human long bones and observationally is typically absent from common mammalian domesticates. We surveyed previously prepared undecalcified histological sections from 25 species (human n = 221; nonhuman primate n = 24; nonprimate n = 169) to see if 1) drifting osteons were indeed more common in humans and 2) this could be a discriminating factor to identify human bone histologically. We conclude that drifting osteons are indeed more prevalent in human and nonhuman primate bone relative to nonprimate mammalian bone. Two criteria identify a rib or long bone fragment as human, assuming the fragment is unlikely to be from a nonhuman primate given the archaeological context: 1) at least two drifting osteons are present in the cross-section and 2) a drifting osteon prevalence (or as a percentage of total secondary osteons) of ≥ 1%. We present a quantitative histological method that can positively discriminate human bone from nonprimate mammalian bone in archaeological contexts.
Topics: Animals; Humans; Haversian System; Prevalence; Mammals; Histological Techniques; Primates
PubMed: 38394068
DOI: 10.1371/journal.pone.0298029 -
The Journal of Experimental Biology Aug 2023Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone...
Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone replacement resulting in secondary osteons) is thought to occur in regions of low strain as part of bone maintenance or high strain in response to microdamage. However, analyses of remodeling in primates have revealed an unappreciated association with the number of daily load cycles. We tested this relationship by raising 30 male domestic rabbits (Oryctolagus cuniculus) on disparate diets from weaning to adulthood (48 weeks), facilitating a naturalistic perspective on mandibular bone adaptation. A control group consumed only rabbit pellets and an 'overuse' group ate hay in addition to pellets. To process hay, which is tougher and stiffer, rabbits increase chewing investment and duration without increasing bite force (i.e. corpus mean peak strain is similar for the two foods). Corpus remodeling in overuse rabbits was ∼1.5 times that of controls, measured as osteon population density and percentage Haversian bone. In the same subjects, there was a significant increase in overuse corpus bone formation (ratio of cortical area to cranial length), consistent with previous reports on the same dietary manipulation and bone formation in rabbits. This is the first evidence that both modeling and remodeling are simultaneously driven by the number of load cycles, independent of strain magnitude. This novel finding provides unique data on the feeding apparatus, challenges traditional thought on Haversian remodeling, and highlights the need for experimental studies of skeletal adaptation that examine mechanical factors beyond strain magnitude.
Topics: Animals; Rabbits; Male; Bone Remodeling; Mandible; Haversian System; Lagomorpha
PubMed: 37439268
DOI: 10.1242/jeb.245942 -
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 -
Clinical Biomechanics (Bristol, Avon) Aug 2023The morphology of osteocyte lacunae varies in bones of different ages and bone pathologies. Osteocyte lacunae can cause stress concentration and initiate microcracks....
BACKGROUND
The morphology of osteocyte lacunae varies in bones of different ages and bone pathologies. Osteocyte lacunae can cause stress concentration and initiate microcracks. However, the influence of changes in osteocyte lacunar shape on microcrack is unknown. Therefore, the aim of this study was to determine the effects of osteocyte lacunae with different shapes on microcrack initiation and propagation.
METHODS
Osteon models containing osteocyte lacunae with different shapes were established. The progressive damage analysis method, based on computer simulations, was used to study the evolution of microdamage within the osteon, including the processes of intralaminar and interlaminar microdamage.
FINDINGS
Models with larger DoE values can effectively delay or prevent the formation of linear microcracks, which ensures high fracture toughness of cortical bone. It is subjected to stronger mechanical stimulation, making it more sensitive to loads. Models with smaller DoE values increase the load threshold for microdamage generation and reduces its impact on bone mechanical performance, making it less susceptible to microdamage than models with larger DoE values.
INTERPRETATION
These findings enhance the limited knowledge of the influence of the lacunar shape on microdamage and contribute to a better understanding of bone biomechanics.
Topics: Humans; Osteocytes; Cortical Bone; Biomechanical Phenomena; Cognition; Computer Simulation
PubMed: 37611387
DOI: 10.1016/j.clinbiomech.2023.106072 -
Archives of Plastic Surgery Sep 2023The outcome of alveolar grafting with synthetic bone substitute (Osteon III) in various bone defect volumes is highlighted. A prospective study was accomplished...
The outcome of alveolar grafting with synthetic bone substitute (Osteon III) in various bone defect volumes is highlighted. A prospective study was accomplished on 55 patients (6-13 years of age) with unilateral alveolar bone cleft. Osteon III, consisting of hydroxyapatite and tricalcium phosphate, is used to reconstruct the defect. Alveolus defect diameter was calculated before surgery (V1), after 3 months (V2), and finally after 6 months (V3) postsurgery. In the -test, a significant difference and correlation between V1, V2, and V3 are stated. A value of 0.01 is considered a significant difference between parameters. The degree of cleft is divided into three categories: small (9 cases), medium (20 patients), and large (26 cases).The bone volume of the clefted site is divided into three steps: volume 1: (mean 18.1091 mm ); step 2: after 3 months, volume 2 resembles the amount of unhealed defect (mean 0.5109 mm ); and the final bone volume assessment is made after 6 months (22.5455 mm ). Both show statistically significant differences in bone volume formation. An alloplastic bone substitute can also be used as a graft material because of its unlimited bone retrieval. Osteon III can be used to reconstruct the alveolar cleft smoothly and effectively.
PubMed: 37808326
DOI: 10.1055/a-2113-3084 -
Journal of the Mechanical Behavior of... Sep 2023This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To...
This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, which represented osteons and interstitial tissue, loaded in uniaxial tension. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber "families." Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created by modeling aging via the following changes to the input parameters: (i) increasing porosity from 5% to 15%, (ii) increasing the ratio of the number of osteon fibers relative to interstitial fibers from 40% to 50%, and (iii) changing the fiber material properties from representing mature bone samples to representing elderly bone samples (i.e., increased strength and decreased toughness of interstitial fibers together with decreased toughness of osteon fibers). To understand the respective contributions of these changes, additional models isolating one or two of each of these were also created. From the computed stress-strain curve for the fiber bundle, the yield point (ϵ, σ), ultimate point (ϵ, σ), and toughness (U) for the bundle as a whole were measured. We found that changes to all three input parameters were required for the model to capture the aging-related decline in cortical bone mechanical properties consistent with those previously reported in the literature. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the material properties of osteon and interstitial tissue, in order to further understanding of aging-related changes in bone.
Topics: Humans; Aged; Porosity; Bone and Bones; Cortical Bone; Aging; Models, Theoretical; Haversian System
PubMed: 37499524
DOI: 10.1016/j.jmbbm.2023.106029