thigh and smallest (stapes) inside the ear.
Bones, together with skeletal muscles, tendons, and joints, allow three-dimensional movement of the body. They provide protection to multiple internal organs, for example, lungs and heart inside the rib cage. Bone marrow is the site of production of all types of blood cells (a process called hematopoiesis). Another function is the storage of nutrients: lipids, serving as a reservoir for energy; and minerals, especially calcium and phosphorus, which are required for multiple cellular actions throughout the body. Bones also have a role in transduction of sound, maintenance of acid base balance, and detoxification of heavy metals.
Structure
Compact, or cortical, bone forms the outer covering of most bones. It is denser than trabecular bone and is responsible for facilitating bones’ main functions. It makes up 80 percent of the total bone mass in the body. Trabecular, or cancellous, bone is a spongy network that is highly vascularized. It contains the bone marrow, which is the primary site of blood cell formation. Examples include ends of long bones.
Cells
Osteoblasts are the immature cell types and are responsible for formation of new bone. They produce certain chemicals (alkaline phosphatase and prostaglandins), which favor the mineralization of bone, and they themselves mature into adult bone cells. Osteocytes are the mature cells. They manufacture the bone matrix in the surrounding space and maintain the calcium stores. The primary function of osteoclasts is the recycling of bone. They produce certain enzymes like acid phosphatase, which break down the mineral surface and allow for the remodeling of bone by osteoblasts.
Types
Depending upon anatomy, the following is true:
Long bones have a central shaft, known as the diaphysis, and the ends with the growth plates, known as epiphyses. The compact bone is thick and covers the spongy bone. Their characteristic feature is that they are much longer than they are wide. Long bones include most of the limb bones like the humerus, radius, and ulna (of the upper limb) and the femur, tibia, and fibula (of the lower limb), including those of the hands and feet, namely, metacarpals and meta tarsals.
Short bones have a thin, compact bone surrounding the spongy bone. They have roughly the same width as their length. Short bones include those of the ankle and wrist joints, called carpals and tarsals.
Flat bones have two parallel layers of compact bone covering the spongy bone. These include the skull bones (cranium), breast bone (sternum), hip bone (pelvis), and ribs.
Irregular bones are mostly made up of cancellous bone and have a thin covering of compact bone. The bones of spine (vertebrae), sacrum and lower jaw (mandible) are irregular bones.
Sesamoid bones are fixed within tendons. They are either short bones or irregular. The knee cap (patella) is a sesamoid bone and it is embedded in the quadriceps tendon.
Depending upon embryonic development, the following is true:
Intramembranous bones are the flat bones (for example, skull bones) and some irregular bones (e.g., the jaw bone, “mandible”).
Endochondrial bones can be long (limb bones, e.g., femur), short (wrist and ankle bones), and irregular bones (vertebrae); all undergo endochondrial ossification.
Development
Bone development, known as osteogenesis, starts early on in the fetal age by unspecialized mesenchymal stem cells (MSCs), which later develop into the precursors of bone cells known as osteoprogenitor cells. By the end of week eight of gestation, the basic structure of the skeleton is laid down. At this stage the skeletal structure is either made up of thin membranes or soft flexible cartilage. During the third month, the hardening of this fragile fetal skeleton begins through ossification. Bone formation and remodeling continues throughout life.
Ossification can occur by one of two processes. The first is intramembranous ossification, which involves mineralization of the sheet-like membranes made up of connective tissue. Initially, some of the stem cells differentiate into osteoblasts. These osteoblasts lay down a highly vascularized spongy bone tissue in the center. With time, these osteoblasts mature into osteocytes and lay down the hard, dense bony matrix. Mineralization results in the formation of cortical bone. The outermost membranous sheet forms the periosteum (outermost single-layered covering of the bone).
The other form of ossification is endochondral ossification. Bones developed in this manner have an initial model made of hyaline cartilage. This cartilage later ossifies, during the third month of gestation. The outermost layer of hyaline cartilage is infiltrated by blood vessels and osteoblast, leading to formation of periosteum. Osteoblasts then penetrate the cartilage in the diaphysis (shaft of a long bone) and replace it with cancellous bone, forming a primary ossification center. This newly formed cancellous bone is later broken down to form the medullary cavity. The ends of the bones, called epiphyses are the sites of secondary ossification centers, which only produce the spongy bone, and not the medullary cavity. The spongy bone at the secondary center ossifies after birth. A layer of hyaline cartilage is retained over the surface of epiphysis (articular cartilage), and between the epiphysis and diaphysis (epiphyseal cartilage). Articular cartilage forms part of a joint. Epiphyseal cartilage serves as a growth region.
Even though the length of bones stops increasing at a certain point, they are capable of growing in thickness throughout life. The action of bone cells is under the control of hormones and paracrine signaling—the process of communication between adjacent cells. Osteoblast action is stimulated by growth hormone, thyroid hormone, estrogen, and androgens. Osteoclast action is stimulated by a chemical (interleukin-6) secreted by osteoblasts and it is inhibited by the hormone calcitonin.
Figure 1 Structure of a long bone
Source: Blausen Gallery 2014. Wikidiversity Journal of Medicine.
Regeneration
Regeneration is a process by which the cells of living tissues are renewed after any loss or damage to the configuration or functional ability of that specific tissue. This process is essential for a healthy, effective functioning of all the body systems in conjunction with each other. Almost all tissues of the body are capable of regenerating on their own after an injury.
Endogenous bone regeneration is a complicated process that is required for the repair of any bones that might be damaged due to trauma, infection, or malignancy—with this process being most effective in fracture healing. It is affected by environmental factors, and a healthy blood supply is imperative to the intrinsic mechanisms responsible for bone healing. These involve a number of signaling pathways that re-orchestrate the process of intramembranous and endochondral ossification. The osteoprogenitor cells, which arise from the mesenchymal stem cells (MSCs), lie at the root of this entire mechanism. When a portion of bone is damaged or injured due to any reason, the osteoprogenitor cells—contained within the periosteum and the bone marrow—give rise to the osteoblasts, which, after proliferation, deposit the bone matrix around themselves and cause mineralization, forming a new bone in its place. Unlike the soft-tissue regeneration process, bones heal without the formation of a scar, hence ensuring the unhindered functioning of the movement apparatus of the body.
However, there are situations in which the intrinsic ability of the MSCs falls short of that required for a certain condition like a large bone traumatic injury, a serious infection, osteoporosis, the healing required after the resection of a bone tumor, or when the blood supply to the bone is compromised. In these conditions, the botched regeneration effort results in the bones becoming scarred, leading to mal-union. Nowadays, there are multiple methods to enhance this impaired regeneration of bone; some are under intensive research, and some are already being practiced. These include the following.
Bone