Читать книгу Fractures in the Horse - Группа авторов - Страница 28

Bone matrix is a two‐phase composite consisting of an organic component, which is synthesized and secreted by osteoblasts, and mineral. The matrix of lamellar bone makes up more than 90% of its volume, the rest being cells, cell processes and blood vessels.

The matrix undergoes mineralization as soon as it is secreted and reaches 70–80% of its final mineral density (around 65% dry weight) within approximately three weeks. Remaining water within the matrix is then progressively substituted by mineral over the ensuing months or years, resulting in the steady increase in mineral density of the bone as it ages. This is easily appreciated on microradiographs in which the relative age of different areas of the cross‐section of the bone can be determined by their radiopacity (Figure 2.4). Regulation of mineral volume fraction varies between and within bones and influences material properties such as stiffness and toughness, which have important functional consequences.

The principal structural component of the organic phase is type I collagen whose fibres are configured to form one of several different microstructures.

Woven bone describes a microstructure that is associated with relatively loosely packed, large diameter collagen fibres that are orientated haphazardly within the matrix. It has a high density of osteocytes, which vary in size, orientation and distribution. It mineralizes rapidly although relatively unevenly. Woven bone is formed relatively quickly and is usually present in bone undergoing rapid expansion (e.g. embryos and neonates) or in fracture callus. It is relatively weak.

Figure 2.4 Microradiograph of a 100 μm thick, undecalcified section of cortical bone from the proximal diaphysis of the humerus of a two‐year‐old Thoroughbred racehorse that had suffered a catastrophic fracture. Different grey levels reflect mineral density of the matrix. Note lightly mineralized periosteal new bone to the right (dark grey), moderately mineralized ‘young’ secondary osteons (variable densities of grey) and most densely mineralized primary bone (which appears almost white).

Conversely, collagen fibres in lamellar bone are laid down in a highly organized fashion around a plexus of blood vessels. Organic matrix is deposited as thin sheets, or lamellae, each approximately 5 μm thick. The orientation of collagen fibres is largely parallel within each lamella and may be the same or vary between successive lamellae. Osteocytes are present in lower density than woven bone, but are more evenly distributed and are of consistent size and orientation. Lamellar bone may be deposited around part or the entire outer circumference and inner endosteal surface of a bone (circumferential lamellar bone) or may form as concentric lamellae within the small tubular subunits of osteons (Figure 2.5). Osteons are formed during the primary growth of bone around a small central Haversian canal that contains neurovascular components. Lamellar bone has superior mechanical properties to woven bone but is formed more slowly.

A combination of these different matrix organizations is found in a microstructure that is common in long bones of the distal limbs of horses and other animals that have evolved to ambulate soon after birth. Woven bone is deposited at the periosteal surface to form waves or folds that grow out radially several hundred micrometres before branching out circumferentially. Adjacent folds meet to form bridges or domes that enclose a small volume of periosteal soft tissue, which usually includes several blood vessels. Lamellar bone then forms on the interior surface of the woven bone, replacing the soft tissue, to form primary osteons that are elongated around the circumference of the bone and which often contain multiple vessels and associated canals (Figure 2.6). This microstructure is referred to as laminar or plexiform bone and it reflects an evolutionary compromise whereby the rate of bone apposition is accelerated with little detriment to material properties [11].

Figure 2.5 Composite photomicrograph of a transverse section through the lateral margin of the cortex from the mid‐diaphysis of the third metacarpal bone from a two‐year‐old Thoroughbred racehorse. Fluorescent dyes administered systemically to the horse at different times before it died demarcate the mineralization front at the time of administration. Several different bone microstructures are present: (i) circumferential lamellar bone (top left), (ii) Plexiform bone and primary osteons (top right) and (iii) secondary osteons at different stages of formation (bottom half of image). Periosteal surface to the top and palmar to the left. Field width is approximately 10 mm.

Figure 2.6 Diagrammatic illustration of plexiform bone, based on the histological appearance of a transverse section through the cortex of the third metacarpal bone from a neonatal Thoroughbred. Plexiform bone develops around a woven bone template (light shade). Buds of woven bone (dark shade) grow radially outwards for approximately 300 μm from the periosteal surface before expanding circumferentially to join with neighbouring radial struts, thereby forming a three‐dimensional mesh of successive layers of bone linked by radial struts. The spaces that remain within the network fill more slowly with lamellar bone to form primary osteons.

Source: Riggs and Evans [10]. Reproduced with permission of John Wiley & Sons.

Accretion of new bone at periosteal and/or endosteal surfaces can increase the thickness, overall diameter and mass of the bone. Alternatively, accretion at one surface and simultaneous resorption at another can alter the geometric properties of the bone, increasing its overall diameter for a similar mass of tissue or redistributing a similar mass around the circumference of the shaft (Figure 2.7). Both processes are termed modelling and occur during growth and as a response to changes in the bone's mechanical environment.

Figure 2.7 The geometric properties of bone can be modified through the coordinated action of osteoblasts and osteoclasts, which deposit (red areas in the diagram) and resorb (grey areas) bone at existing surfaces to alter the overall geometry of the bone. This process is called modelling.

Groups of osteoclasts may be recruited to foci on the surface of or within the bone matrix and stimulated to resorb tissue, either as surface layers or as tunnels through the matrix. In the latter case, osteoclasts cut tubes, ‘resorption canals’ approximately 250 μm in diameter, through the bone. The canals are typically orientated parallel to the long axis of the bone, extend over several millimetres and may branch several times (Figure 2.8). Under normal circumstances, osteoclasts and osteoblasts work in synchrony, the latter following the resorptive front, forming fresh matrix on the recently ‘cut’ surface. Osteoid is deposited as sheets, lamellae, in which collagen fibres are aligned in parallel (Figure 2.5). Successive lamellae, between which the alignment of collagen fibres relative to the long axis of the bone may vary, form layers on the surface of bone or around the inner circumference of the resorption canals until only a small central hole that contains blood vessels and lymphatics (the Haversian canal) remains. The resultant structure is called a secondary osteon. This process, whereby osteoclasts are activated and bone is resorbed and subsequently replaced at the same location with fresh tissue, is called remodelling, and the functional unit of cells that performs it is referred to as a basic multicellular unit (BMU). The deepest margin of resorption, where new bone abuts pre‐existing tissue, is called the reversal line and is demarcated by a line of cement, a thin layer of amorphous matrix that joins fresh bone to old. This is an important structural feature in relation to a bone's ability to resist fatigue as it acts to ‘capture’ small cracks that may develop within bone and so prevent their further extension.

Figure 2.8 Diagrammatic representation of an isolated secondary osteon complex in longitudinal (left) and transverse sections, illustrating its branching course and different stages of development. The branch to the right illustrates a group of mobilized osteoclasts that are resorbing bone in a coordinated manner to form a tunnel. Osteoblasts follow secrete successive layers of osteoid on the walls of the tunnel, progressively filling it in to form a secondary osteon.

Source: Riggs and Evans [10]. Reproduced with permission of John Wiley & Sons.

Remodelled bone, containing a high proportion of secondary osteons, is typically weaker and less stiff than the primary tissue that it replaced. This begs the question of the functional (evolutionary) value of remodelling. For many years, the primary physiological role of remodelling was thought to relate to mineral homeostasis: resorption of bone provides a rapid supply of calcium ions from the skeleton to meet systemic metabolic requirements. More recently, focus has shifted to the role of remodelling in maintaining the structural integrity of bone as a load‐bearing tissue: it is a mechanism whereby damaged matrix can be removed and replaced with fresh, healthy tissue [12, 13]. A large proportion of researchers interested in the effects of loading on bone support the concept of microdamage as a common phenomenon. Minute cracks (micrometres in length) in bone matrix, regularly illustrated in publications and frequently associated with previous loading, are purported to represent localized damage as a consequence of loading [14, 15]. In addition, there is growing support for the hypothesis that damage to the matrix induces apoptosis of surrounding osteocytes, which in turn acts as a stimulus for localized recruitment and activation of osteoclasts [16]. This provides an elegant physiological mechanism whereby remodelling is specifically targeted to repair damage at varying scales of magnitude: bone that contains cracks is removed and replaced with healthy tissue. However, this hypothesis is not universally accepted and some argue that, in most cases, ‘microdamage’ is no more than an artefact created by the techniques used to study it and that there is no evidence that remodelling is directly coupled to damage [17]. Boyde has provided evidence from clinical material from a number of species, including the horse, to illustrate that when they do occur, microcracks can be effectively managed physiologically and mechanically through alternative means that include bonding cracks by filling them with mineral‐rich matrix and ‘bandaging’ trabeculae with surface new bone [17]. It is not inconceivable that both mechanisms of repair occur, the balance being determined by the loading environment.

Remodelling also provides a mechanism through which bone can be ‘fine‐tuned’ so that its microstructure, as well as macrostructure, is modified to best match prevailing mechanical demands: a form of ‘microadaptation’. For instance, primary bone in the caudal cortex of the equine radius, which contains predominantly longitudinally orientated collagen fibres, is largely remodelled within the first two to three years of life and replaced with secondary osteons containing predominantly transversely orientated fibres, which are more suited to resist the compressive strains that predominate at this location [18].