Studies on the Mechanism of Callus Cartilage Differentiation and Calcification During Fracture Healing

Ketenjian, Ara Y.; Jafri, Ali M.; Arsenis, Charolampos

doi:10.1016/s0030-5898(20)30880-4

Cited by 28 publications

(5 citation statements)

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“…The cartilage in the fracture callus is usually described as fibrocartilage (Ham & Harris 1971), though this term was used only for initial fibrous tissue around the fracture by Ketenjian et al (1978). Fibrocartilage has a well-organized matrix in which thick collagen fibrils occur in bundles with a preferred orientation (Bloom & Fawcett 1975).…”

Section: Cartilage and The Fracture Callusmentioning

confidence: 99%

The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study

Ashhurst

1986

Phil. Trans. R. Soc. Lond. B

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To examine in detail the events that lead to healing under different mechanical conditions, experimental fractures of the rabbit tibia were immobilized with either a metal compression plate or a plastic plate, to produce stable or unstable mechanical conditions respectively. To fracture the bone, a small saw cut is made in the medial cortex and three-point pressure is then applied to fracture the remaining cortical bone. A small amount of bone is removed by the saw cut. This is of no consequence when a plastic plate is used because the plate is designed so that a small gap remains between the fractured surfaces. When a compression plate is used, a gap approximately 100 pm wide remains under the plate. In addition, despite the use of compression, only part of the fractured surfaces are normally in contact, so other narrow fracture gaps may remain. The fractures were examined at experimental times from 4 days to 1 year by both light and electron microscopy. In stable mechanical conditions, a thin layer of periosteal callus starts to form within 4 days and healthy mesenchymal cells and capillaries are adjacent to the fracture. By 7 days the callus is fully developed and is covered by a new periosteum. Over the following weeks it becomes more compact as the cavities are filled by bone. The endosteal callus, if formed, is small. From 9 days onwards the fracture gaps of between 30 and 100 pm are invaded by mesenchymal cells; macrophages remove the debris and fibroblasts lay down a collagenous matrix. Capillaries are numerous. By 2 weeks, these gaps are lined by osteoblasts producing transverse layers of new bone on the fractured surfaces. The gap is rapidly filled by transversely orientated bone to achieve union by 3-4 weeks. Resorption is limited to very small, isolated regions of the fractured surfaces. The gaps between 10 and 30 μm wide appear to be too narrow for cells and capillaries to enter, and they are widened by osteoclastic action. Mesenchymal cells and capillaries then enter and bone is laid down on the surfaces of the newly excavated cavities. After union, the region is recognized as a wide band of irregularly organized bone. In compressed regions, areas of actual contact are very few, and narrow gaps can be seen. Union is achieved by direct Haversian remodelling across gaps up to 9 pm wide. Remodelling starts at about 3 weeks and it is part of the normal process that occurs after union of a fractured cortex. The events in the fractures healing under unstable mechanical conditions diverge immediately. The initial periosteal reaction is similar, but cancellous bone forms only away from the fracture gap. Mesenchymal cells in a fibrous matrix, but with very few, if any, associated capillaries, persist as a thick layer over the fracture gap. At 6 days islands of cartilage begin to develop, and by 12 days the whole central area is filled by a cartilaginous matrix containing thick and thin collagen fibrils and elastic fibres. The cartilage is replaced by bone by 3-4 weeks. At this point, healthy cells and capillaries are found near the fracture gap. A small endosteal callus may form in a similar way. The fracture gaps are now invaded. The debris is removed by macrophages, and fibroblasts produce a collagenous matrix. Osteoclasts cover the fractured surfaces, but the amount of resorption is minimal. Capillaries also enter the gap. Within 1-2 weeks the gap is filled by transverse lamellae of bone. Once the fractured cortex is united, the events are similar in both series of fractures. Resorption of any callus starts. In the periosteal callus, large cavities form particularly along the callus-cortex junction. Over the next 3 months the callus is resorbed and the cortex is extensively remodelled. By 18 weeks no callus remains. The cortical bone is compact, but large cavities filled with fat cells may occur. The overall dimensions of the bone may be larger than that of the contralateral normal tibia, but the layer of cortical bone is thinner. Thus the plate, whether of metal or plastic, affects the structure of the bone. This study serves to emphasize that the mechanical stability of a healing fracture determines the composition and size of the periosteal callus and the time at which union across a fracture gap is achieved. The fracture fragments must be mechanically stable, so that there is no movement at the fracture gap before cells can enter and lay down new bone. This may be achieved immediately, though artificially, by a metal compression plate, or slowly, though naturally, by the formation of a large callus of cancellous bone. The movements and differentiation of the cells involved in healing are discussed. This experimental fracture model will form a basis for future experimental studies of healing fractures.

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Section: Cartilage and The Fracture Callusmentioning

confidence: 99%

The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study

Ashhurst

1986

Phil. Trans. R. Soc. Lond. B

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“…While there was some initial controversy, it soon became apparent that these structures are typically invested by a trilaminar membrane; thus the name, "matrix vesicles -MVs", became their accepted title. Since their initial discovery in growth plate cartilage, MVs have been found to be the locus of the first mineral deposits in intramembranous bone formation (5), in fracture callus (6)(7)(8), in developing dentin (5,9), in developing deer antler (10), in pathological calcifications in Figure 1. Sudan Black B Staining of Growth Plate Cartilage.…”

Section: Introductionmentioning

confidence: 99%

Matrix vesicles: structure, composition, formation and function in calcification

Wuthier

Lipscomb²

2011

Front Biosci

158

230

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Matrix vesicles (MVs) induce calcification during endochondral bone formation. Experimental methods for structural, compositional, and functional analysis of MVs are reviewed. MV proteins, enzymes, receptors, transporters, regulators, lipids and electrolytes are detailed. MV formation is considered from both structural and biochemical perspectives. Confocal imaging of Ca(2+) and H(+) were used to depict how living chondrocytes form MVs. Biochemical studies revealed that coordinated mitochondrial Ca(2+) and Pi metabolism produce MVs containing a nucleational complex (NC) of amorphous calcium phosphate, phosphatidylserine and annexin A5--all critical to the mechanism of mineral nucleation. Reconstitution of the NC and modeling with unilamellar vesicles reveal how the NC transforms into octacalcium phosphate, regulated by Mg(2+), Zn(2+) and annexin A5. Extravasation of intravesicular mineral is mediated by phospholipases and tissue-nonspecific alkaline phosphatase (TNAP). In the extravesicular matrix, hydroxyapatite crystal propagation is enhanced by cartilage collagens and TNAP, which destroys inhibitory PPi, and by metalloproteases that degrade proteoglycans. Other proteins also modulate mineral formation. Recent findings from single and multiple gene knockouts of TNAP, NPP1, ANK, PHOSPHO1, and Annexin A5 are reviewed.

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“…In healthy patients, this proinflammatory state is necessary for normal bone healing by enhancing extracellular matrix (ECM) synthesis, angiogenesis and recruiting mesenchymal stem cells (MSCs) to form bone. 29 , 30 Patients with DM and neuropathy may have a prolonged and unabated proinflammatory state due to continued trauma from weight-bearing on an injured limb. The normal orderly sequence of bone healing may be disrupted due to alteration in perfusion, chondrocyte imbalances, RAGEs, and increased osteoclast activity.…”

Section: Bone Health In Dm and Fracture Healing Physiologymentioning

confidence: 99%

Fractures and dislocations of the foot and ankle in people with diabetes: a literature review

Johnson

Kandasamy

Raspovic

et al. 2023

Therapeutic Advances in Endocrinology

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Diabetes (DM) increases fracture risk, and bone quality depends on type diabetes type, duration, and other comorbidities. Diabetes is associated with a 32% increased relative risk (RR) of total fractures and 24% increased RR of ankle fractures compared with patients without DM. Type 2 DM is associated with a 37% increased RR of foot fractures compared with patients without DM. The incidence of ankle fractures in the general population is 169/100,000 per year, while foot fractures occur less frequently, with an incidence of 142/100,000 per year. Biomechanical properties of bone are negatively impacted by stiff collagen, contributing to the increased risk of fragility fractures in patients with DM. Systemic elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin-1β (IL-1β), and interleukin 6 (IL-6), impact bone healing in patients with DM. Fractures in patients with DM, can be associated with poorly regulated levels of RANKL (receptor activator of nuclear transcription factor kappa-b ligand) leading to prolonged osteoclastogenesis, and net bone resorption. One of the most salient factors in treating fractures and dislocations of the foot and ankle is to recognize the difference between patients with uncomplicated and complicated DM. Complicated diabetes is defined as ‘end organ damage’, and for the purposes of this review, includes patients with neuropathy, peripheral artery disease (PAD) and/or chronic renal disease. Uncomplicated diabetes is not associated with ‘end organ damage’. Foot and ankle fractures in patients with complicated DM pose challenges, and surgery is associated with increased risks of impaired wound healing, delayed fracture healing, malunion, infection, surgical site infection, and revision surgery. While patients with uncomplicated DM can be treated like patients without DM, patients with complicated DM require close follow-up and robust fixation methods should be considered to withstand the anticipated prolonged healing period. The aims of this review are as follows: (1) to review pertinent aspects of DM bone physiology and fracture healing, (2) to review the recent literature on treatment of foot and ankle fractures in patients with complicated DM, and (3) to provide treatment protocols based on the recent published evidence.

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Studies on the Mechanism of Callus Cartilage Differentiation and Calcification During Fracture Healing

Cited by 28 publications

References 0 publications

The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study

The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study

Matrix vesicles: structure, composition, formation and function in calcification

Fractures and dislocations of the foot and ankle in people with diabetes: a literature review

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