The Composition and Development of Bone

Levesque 1 The Composition and Development of Bone Bone is a rigid organ which provides the framework and support for the human body. It is formed while still in the foetus from a cartilaginous precursor. During development, the composition of the cartilage changes into bone and becomes more solid. Bone is designed to withstand the strain of day to day physical activity. However sometimes the strain exceeds the bone’s limitations, which is precisely why living bone has the ability to repair itself. This essay will discuss the composition, development, structure, and healing of bone. Bone is composed of organic matter, mineral and water. At the molecular level, the organic matter consists of 90% of Type I collagen molecules. These molecules are organized into three stretched helical amino acid chains which are twisted into triple helixes, each approximately 300 nm in length and 1.5 nm in diameter. Every third amino acid is made up of glycine, which amounts to 33% of the makeup of collagen. Another 20% resides in high levels of proline and hydroxyproline. Triple helixes, or triplets, are organized into bundles called microfibrils. These are about 20 nm in diameter when initially created, but grow to about 90 nm. The average young adult will have a microfibril with a diameter of 75 nm. Microfibrils bundle together to form fibres which again bundle to form quasi-hexagonal packing. Due to the organized arrangement of the fibres, the ionic and hydrophobic interactions between neighbouring amino acids chains, and a certain amount of cross-linking between molecules, the collagen is insoluble under normal circumstances. Other factors assisting in this are the strong aldehyde cross-links formed between the lysine and hydroxylysine of adjacent collagen molecules as well as the intramolecular hydrogen bonds that stabilizes the microfibrils. The remaining 10% of the organic matter include mucopolysaccharides and non-collagenous proteins, such as osteocalcin (Turner-Walker, 2008). The bulk of a bone’s strength comes from its mineral component, hydroxyapatite. It is a form of calcium phosphate and is recognized as being stoichiometrically imperfect and contains carbonate. Its composition correspondent to Ca (PO₄)₆(OH) , also called bioapatite. Hydroxyapatite crystals are plate-like in morphology and its dimensions are currently estimated to be 35 nm by 5nm and a thickness of 2-3 nm. As the bone matures, the hydroxyapatite crystals will increase in size. The hydroxyapatite crystals are embedded in the collagen matrix where their c-axes are parallel to the long axis of the collagen fibres. The site Levesque 2 of primary mineralization for the hydroxyapatite crystals is found within gaps between the collagen fibres. The secondary mineralization, the majority of the mineral load, progressively fills the interfibrillar spaces. The non-collagenous protein osteocalcin binds to both hydroxyapatite and collagen molecules. It ultimately strengthens the union between the two (Turner-Walker, 2008). The overall structure of the bone consists of the shaft which is called the diaphysis, and the ends of the bone which are the epiphyses. Healthy bones are made up of two distinct components: cortical and spongy bone. The cortical, or compact bone, makes up the dense outer layer which provides the essential strength of the bone. Compact bone at joints can be covered by cartilage during life which is then called subchondral bone. Spongy bone, also known as cancellous or trabecular bone is lightweight and porous. It is within the cancellous bone that the red marrow forms. During growth, the red marrow will recede to give way to the yellow marrow which is found in the medullar cavity. The outer surface of the bone is either covered with cartilage or a thin tissue called periosteum. The periosteum is a tough membrane which nourishes the bone. The inner surface of the bone is covered with a membrane called endosteum. Both of these membranes are referred to as osteogenic tissue since they contain bone-forming cells (White, 2005). In utero, bone will form using one of two processes, the intramembranous or endochondral ossification. Intramembranous bone begins developing from the embryonic connective tissue. This occurs in flat cranial bones, the clavicle, and the bone collar surrounding the shaft of cartilage models. Endochondral ossification begins forming around week 5 of post-fertilization with the formation of hyaline cartilage models from embryonic connective tissue. As the cartilage expands, the central part dehydrates and will then enlarge, die, and calcify. Simultaneously, blood vessels will bring bone-forming cells to the waist of the cartilage model. A collar of bone forms around the cartilage shaft within the intramembranous ossification. This forms the new periosteum membrane around the bone collar which now supports the tubular shaft for the cartilage model. The core of the bone continues to degenerate and calcify. Blood vessels go through the bone collar to enter the cartilage model and multiply, directing periosteal osteoblasts into the cartilage model. By week 8 of foetal development, these bone-forming cells are arranged along the edges of calcified cartilage at the ends of the shaft, the primary ossification centres. While they create new bone, the blood absorbs the disintegrating calcified cartilage and in so replaces cartilage with endochondral bone. Calcified cartilage as well as some endochondral bone is Levesque 3 subsequently absorbed to form the medullary or marrow cavity. The marrow cavity then fills with red marrow in foetus. The cartilage will continue to be replaced with bone for the rest of the individual’s time of growth, which is roughly the next 16 to 25 years (Kapit and Elson, 2002). Secondary centres of ossification begin to form in the first few years after birth. These centres are located in the epiphyses as the blood vessels penetrate the cartilage there. The cartilage that remains between the epiphyses and diaphysis becomes the epiphyseal plate. This cartilage continues to grow as its ends are ossified, a process which makes the individual grow taller. Eventually, the epiphyseal plate will fuse, concluding the longitudinal growth period (Kapit and Elson, 2002). Osteoclasts reabsorb unnecessary bone in order to make room for fresh bone. Osteoblasts are the cells responsible for producing and depositing bone material. Just beneath the periosteum they create prebone tissue known as osteoid. The osteoid is an organic matrix rich in collagen which is later calcified when crystals of hydroxyapatite are deposited in the matrix. (White, 2005). When osteoblasts have completed their required bone formation, the majority of them perform a cell programmed death referred to as apoptosis. The remaining osteoblast become osteocytes or bone lining cells. Osteocytes are the cells which give the signal of when to create or reabsorb bone, and they are the most abundant type of bone cell (Waldron, 2009). Bones which forms at a higher speed than usual do not develop in the normal way, this type of bone is known as woven or fibre bone. Woven bone is not as dense or as well organized as normal bone due to the irregularity in the thickness and orientation of the collagen microfibrils. Woven bone is associated with fracture callus, neoplasms (cancer), infections found beneath the periosteum, or more commonly, during the initial growth of the skeleton (Turner-Walker, 2008). Primary bone can be divided into three categories: primary lamellar, primary osteon, and plexiform. Lamellar, or normal bone is organized circumferentially around the endosteal and periosteal surface. It is dense due to its multiple layers. An osteon is when lamellar bone surrounds a central canal which conveys a blood vessel forming a concentric structure. Plexiform is similar to cancellous bone, but is highly organized. Haversian systems are the arrangement of cortical osteons. They are supplied with blood through the central canal, as well as the Volkmann canals. The Volkmann canals allow the blood to pass from the Levesque 4 periosteum to link with the Haversian systems. Primary osteons form during the initial bone development, but are later replaced by secondary osteons which are larger (Waldron, 2009). As bone tissue matures, osteons change in density and cross-section which can be observed in histological sections of biological tissues. The study of histology can help determine the age at death of an individual based on calculating the remodelling rate from the cortical bone. The remodelling rate can be calculated by recording the number of intact osteon density, fragmentary osteon density, remodelling osteons, average osteonal crosssectional area, average osteonal cross-section diameter, average area of Haversian canal, and percentage of osteonal bone (Turner-Walker and Mays, 2008). Pfeiffer et al. (1995) discovered that histological analyses would vary depending on where the sample originated. Samples were taken from the different quadrants of the femur: anterior, posterior, medial and lateral. The study found that there were divergences between the periosteal and endosteal bone in the femur. This could be due to the differences in mechanical loading. Further studies by Maat et al. (2006) has suggested that the method performed better when the transverse section was taken at the most anterior portion of the femur diaphysis and at points 25° to the left and to the right (a wedge-shaped section). Furthermore, they studied the percentage of non-remodelled circumferential lamellar bone near to periosteal surface as opposed to counting the whole and partial osteons. It was also found that sex did not play a factor in the determination of age at death, though the margin of error was +/- 11 years (Maat et al. 2006). Despite these results, many osteologists prefer the use of rib sections as opposed to femur sections because theribs have the benefit of not being a load bearing bone which could potentially skew the results. Nevertheless, there are many factors influencing the results from a histological study such as genetics, ethnicity, activity patterns, diet and hormonal influences (Turner-Walker and Mays, 2008). Living bone is constructed to withstand a large amount of mechanical force due to its rigidity and slight elasticity. The bone is also equipped to heal and remodel itself when it fractures. The first phase of healing is the inflammatory stage where the haematoma coagulates 6 to 8 hours after the initial break (Bennike, 2008). While the tissue debris is being removed by macrophages and other cells, the osteoblasts synthesize type I collagen, the released fibroblast growth factor stimulates the proliferation of fibroblast, and there is new vessel formation to allow more blood to reach the site of injury. This stage lasts up to 72 hours, and is followed by the repairing stage which can last approximately another two Levesque 5 weeks. The formation of osteoblasts within the haematoma leads to the creation of cartilage. The haematoma is converted into a fibrous callus which is linked with the surrounding bone tissue. Osteoblasts in the endosteum produce woven bone in the medullary cavity while the periosteal osteoblasts create a sub-periosteal callus, or woven bone. The healing can initially be perceived by the rounding of the edges of the bone. Halfway through the reparative stage, the remodelling stage begins with the calcification of the callus. The slow process will turn the fibrous callus into normal bone with the anatomically correct histological structure. The remodelling of cancellous bone takes place on the trabeculae which makes the bone thicker. Healing is said to be complete when the marrow cells fill the medullary cavity (Waldron, 2009). The remodelling stage takes the longest amount of time, 6 weeks in children, and 6 months in older adults (Bennike, 2008). Although Waldron (2009) explains that remodelling can continue for up to seven years at which time there will be practically no trace of the fracture remaining. There are multiple factors which can affect the healing rate such as age, vascular supply, fracture type, location of the fracture on the bone, soft tissue interposition, and the type of bone. Spiral fractures heal faster than horizontal fracture, just as the metaphysis and cancellous bone heal faster than the diaphysis and cortical bone. Infections are also known to delay healing due to the pathological processes. It is very important to keep the bone immobile during the healing process since movement stimulates fibrous callus formations which take longer to heal (Bennike, 2008). Although it is common to find well-aligned healed fractures in the archaeological context, a study by Schultz (1967; cited in Bennike, 2008) found that wild gibbons with broken bones could heal naturally without any medical attention or serious misalignment. This supports the idea that some fractures can heal well without medical assistance. Although fractures which do not heal properly can lead to more serious complications such as osteomyelitis, pseudoarthrosis, avascular necrosis of bone, neuropathy, articular changes, and bone shortening to name a few (Bennike, 2008). In summary, bone is made up of minerals and organic matter which mostly consists of collagen fibres. These fibres bundle together multiple times to increase its strength. Bones are designed to endure large amounts of mechanical stress, although they do have their limits. When the bone fractures, the same elements which created the bones during development resurface to create the woven bone before replacing it with normal bone. The bone will remodel itself to return to its former state and proceed with its previous task of supporting the Levesque 6 frame of the body, storing calcium, and forming red blood cells. Bone is a versatile and adaptive organ. Levesque 7 Bibliography Bennike, P., 2008. Trauma. In: R. Pinhasi & S. Mays, eds. Advances in Human Paleopathology. Chichester, England ; Hoboken, NJ: John Wiley and Sons, Ltd, pp. 309-328. Kapit, W. & Elson, L. M., 2002. The Anatomy Coloring Book. 3rd ed. San Francisco: Benjamin Cummings. Maat, G. J. R., Maes, A., Aarents, J. & Nagelkerke, N. J. D., 2006. Histological Age Prediction from the Femur in a Contemporary Dutch Sample. Journal of Forensic Science, Volume 51, pp. 230-237. Pfeiffer, S., Lazenby, R. & Chiang, J., 1995. Brief Communication: Cortical remodeling data are affected by sampling location. American Journal of Physical Anthropology, Volume 96, pp. 89-92. Turner-Walker, G. & Mays, S., 2008. Histological studies on ancient bone. In: R. Pinhasi & S. Mays, eds. Advances in Human Paleopathology. Chichester, England ; Hoboken, NJ: John Wiley and Sons, Ltd, pp. 121-146. Turney-Walker, G., 2008. The chemical and microbial degradation of bones and teeth. In: R. Pinhasi & S. Mays, eds. Advances in Human Paleopathology. Chichester, England ; Hoboken, NJ: John Wiley and Sons, Ltd, pp. 3-29. Waldron, T., 2009. Paleopathology. Cambridge: Cambridge University Press. White, T. D., 2005. The Human Bone Manual. Oxford: Academic Press.