Bone, Ossification and Repair

Bone Tissue

The bone tissue is a particular type of support connective tissue that derives from hyaline cartilage, whose extracellular matrix rich in calcium imprisons the cells that produced it. Calcium is found in the form of tricalcium phosphate, a salt that is deposited in the form of hydroxyapatite crystals. Then there are other salts such as calcium carbonate and calcium fluoride. The TO is then mineralized and this gives it special characteristics: it is a resistant tissue, but has a certain degree of flexibility and lightness. The bone tissue form the bones that make up the skeleton of vertebrates.

Macroscopic Structure

The bone consists of a central part named diaphysis and two rounded ends named epiphysis. During the development of skeleton, between diaphysis and epiphysis is present a layer of cartilage, called conjugation cartilage or growth plate. As long as this cartilage is not mineralized and ossified, bone lengthening is possible.

The bone is also almost totally coated on the outer surface of a membrane of dense and elastic connective named periosteum, consisting of collagen fibers and fibroblasts, and osteogenic cells in contact with the bone which differentiate into osteoblasts; with the the exception of epiphyseal articular surfaces that are coated with an encrustation of hyaline cartilage.

The cavities that are located within the bones are instead covered with a layer of reticular connective with osteoprogenitor cells called endosteum, thinner than the periosteum which has the function of providing nourishment and new bone cells.

Cells

The bone tissue cells are divided into:

Matrix

Even the Bone Tissue, such as all kinds of connective tissue, is made of cells and an abundant proteic matrix produced by cells of the tissue in which the cells themselves are immersed. This matrix is ​​constituted by an organic portion, and an inorganic or mineral component.

The different components of the matrix give different and interdependent properties to the tissue: the calcified fraction is responsible for the hardness of the bone, while the fibrillar is responsible for the flexibility, strength and the tensile strength of the tissue.

Organization of Bones

The Bone tissue may assume a non-lamellar organization which is found in the early stages of bone formation, in the early stages of bone repair, eg. as a result of fracture and on the insertion points of tendons. In this type of organization the collagen fibers are not organized in stratified lamellas but shall run in thick bundles intertwined with gaps irregularly dispersed in the matrix.

The lamellar organization instead is the result of the non-lamellar bone remodeling, that is found in the adult. It consists of layers of parallel lamellae overlapped each other, and the collagen fibers are oriented in the same direction in the same layer and in different directions with respect to the near lamellae. In this type of organization can be distinguished thus:

  • Compact bone formed by bony columns parallel to the major axis of the bone. Each column is in turn formed by concentric layers or lamellae (lamellar bone)
  • Spongy boneconsisting of a network of bony trabeculae separated by a maze of spaces containing the bone marrow.

Classification of bones

According to their shape the bones can be classified as follows into:

  • Long Bones when the major axis is developed in length while the smaller in width (eg the femur). In them there are three areas: the central segment or diaphysis, consisting of compact bone which borders the medullary cavity and continue with the compact bone that lines the epiphysis; the two ends or heads that are called epiphysis consist of spongy bone covered by a sheet of compact bone, and the portion between the epiphysis and diaphysis named metaphysis
  • Short Bones when the two axes are similar (such as the vertebral body). They consist of spongy bone covered by a layer of compact bone
  • Flat Bones when the thickness is significantly below the surface (such as the sternum) and there are two layers: an outer and an inner of compact bone, defined exterior and interior plank, which delimit a central part of spongy bone named diploe

Organization of the bone lamellae

The bone lamellae can be arranged in various ways; for example in the long bones some lamellae forming the outer circumferential system that encloses the bone below the periosteum. Behind the medullary cavity there are other 2-3 lamellae that form the inner circumferential system; between these two systems there are osteons, also called Haversian systems, which look like solid cylinders that have, in longitudinal direction, a cavity that contains blood vessels. The lamellae of osteons are arranged concentrically around the central channel called Haversian channel. The Volkman channels are other vascular channels which run perpendicularly to the major axis of the osteons. Finally other lamellae form a system called interstitial system of bone which is located between the osteons; They are osteons in resorption which thus take a polyhedral shape to adapt to the surfaces of the surrounding osteons.

Ossification

The formation of bone tissue or Ossification is the process of creating bone through the deposition of extracellular material and its calcification and it can occur in two ways:

  • Direct or inter-membranous Ossification
  • Indirect or chondral Ossification

The bone that is formed by the two processes have the same histological structure. Initially it will be the primary bone, which is the immature form present during embryonic development and during the reparative processes (eg. fractures). It has many osteocytes and interwoven collagen fibers, with a lower mineral content than mature bone. Following the primary bone is replaced by secondary or mature bone constituted by parallel or concentric lamellae (osteon).

Growth of long bones

During the growth of the bone, trabeculae of calcified cartilage and their bony coating are reabsorbed thanks to osteoclast activity so that the first sketch of the medullary cavity of the diaphysis constitutes.
So in the long bones the first ossification occurs in the diaphysis. After a period of proliferation, chondrocytes resorb the matrix and increase in volume. Then in the matrix diffuse salts of calcium, collagen, growth factors and osteoclasts that degrade the cartilage invaded by vessels and osteoblasts of the periosteum. The spongy tissue is not reabsorbed but form the marrow. The bony sleeve form the compact lamellar bone tissue that produce more matrix, which extends at the expense of the cartilage. While the cartilage retreats and the compact bone tissue increases, the intermediate zone is called metaphysis or growth plate or conjugation cartilage. The latter for the entire period of the body development extends for interstitial growth on the side facing the epiphysis, while it is simultaneously replaced by bone on the side facing the center of diaphysis.

In conjugation cartilage distinguish different zones which, going from epiphysis to the diaphysis, are:

  • area of the cartilage in rest with isolated cells or in isogenic groups
  • area of proliferation or of seriated cartilage, in which the cartilage cells proliferate and are arranged in longitudinal columns
  • area of cell hypertrophy and enlargement of the gaps
  • area of calcified cartilage
  • area of vascular invasion and bone deposition

Subsequently, the process of ossification extends at both ends of the diaphysis, toward the epiphysis. The final balance occurs when the cartilage remains in a constant quantity. After the age of development the cartilage disappears completely. In short bones you have the same process but the cartilage radiates in all directions, not only toward the epiphysis.

Bone remodeling

After birth in both epiphyses appear the Epiphyseal or Secondary Ossification Centers, in which will be the endochondral ossification. In the epiphysis, when the cartilage cells proliferate give rise to cells that are arranged to form groups or nests, so that an epiphyseal growth in all directions is ensured. The newly formed bony trabecular are not reabsorbed as in diaphysis, but remain giving to epiphysis a spongy appearance. The periosteal sleeve extends throughout the diaphysis and increases in thickness, which allows the increase in thickness and width of the long bones, while the growth in length mainly depends by endochondral ossification of the metaphysis. Then the compact bone, which forms the wall of the diaphysis, in the adult is formed almost exclusively for perichondral ossification first and then periosteal; while the spongy bone that forms the epiphysis is formed exclusively for endochondral ossification.

The regulatory factors of bone remodeling are:

The factors that instead interfere with the process of bone remodeling are:

  • Pregnancy
  • Breast-feeding
  • Menopause
  • Various diseases including Osteoporosis

Bone remodeling
After birth in both epiphyses appear the Epiphyseal or Secondary Ossification Centers, in which will be the endochondral ossification. In the epiphysis, when the cartilage cells proliferate give rise to cells that are arranged to form groups or nests, so that an epiphyseal growth in all directions is ensured. The newly formed bony trabecular are not reabsorbed as in diaphysis, but remain giving to epiphysis a spongy appearance. The periosteal sleeve extends throughout the diaphysis and increases in thickness, which allows the increase in thickness and width of the long bones, while the growth in length mainly depends by endochondral ossification of the metaphysis. Then the compact bone, which forms the wall of the diaphysis, in the adult is formed almost exclusively for perichondral ossification first and then periosteal; while the spongy bone that forms the epiphysis is formed exclusively for endochondral ossification.

Repair of Bone Tissue

When a bone undergoes a fracture, the fragments are removed by macrophages and the wound is filled with granulation tissue, whose cells are recruited in the periosteum and endosteum. This granulation tissue acts as a blastema and generates bone replacement. In a first time in the granulation tissue differentiate some chondroblasts that produce a fibrocartilagineous callus that closes the lesion. In this callus a interwoven bone is formed, because of endochondral ossification inside and subperiosteal deposition at the periphery.
At first are formed trabecular bone which then combine with healthy bone over callus. While the ossification goes on, the fibrocartilaginous callus is replaced by a interwoven bony callus quickly replaced by osteons of mature bone. The phenomenon of remodeling ensures that the new bone tissue is arranged in the most efficient way to withstand the stresses to which it is subjected.
The replacement is more rapid when the damaged surfaces of the fractured bone are aligned properly and when the bone loss is modest. This limits the need for formation of the callus and reduces the need of remodeling.
The repair of bone tissue is a spontaneous physiological process favored by the natural spontaneous and constant turnover of the constituents. Depending on the conditions in which the body is during the reparative phase of the bone, it may be useful to integrate the diet with a supplement able to provide the body with nutrients essential for bone metabolism and in particular for the reparative process, for the reabsorption of any hematoma, for the densely vascularized and innervated periosteum and endosteal vessels.