Bone Homeostasis

Bone Homeostasis

Bone homeostasis is the process of self-repair of the bones, which are active and dynamic types of tissue that undergo continual changes. Between 5% and 7% of bone mass is recycled every week. Each day, up to 500 mg of calcium may enter or leave the skeleton of an adult. Compact bone is replaced every 10 years or so, whereas spongy bone is replaced every 3–4 years. These activities help to avoid bones becoming brit-tle, which occurs when calcium salts slowly crystal-lize over time. Brittle bones are much more likely to become fractured. Bone fracture is the most common disorder of bone homeostasis.

Bone Remodeling

The surfaces of a bone’s periosteum and endosteum experience both bone deposit and resorption in adults. Bone deposit and resorption make up the process of bone remodeling. Groups of nearby osteoblasts and osteoclasts form remodeling units. These units control bone remodeling, assisted by osteocytes, which sense bone stressors. Total bone mass is constant in healthy, younger adults. This means that rates of bone deposit and resorption are in balance. Remodeling occurs in different amounts in various bones. Although the shaft of the femur (thighbone) is remodeled slowly, its distal area is completely replaced within six months.

Bone Fracture

Bone fractures are classified as positioning, complete-ness of the fracture, and penetration of the skin by the bones. Positioning of fractures includes classifications such as nondisplaced fractures and displaced fractures. A nondisplaced fracture means the bone ends remain in their normal position and a displaced fracture means the bones are out of their normal alignment. Regarding the completeness of the fracture, a complete fracture describes one in which the bone is broken completely through (FIGURE 7- 10), whereas an incomplete fracture means the bone is not broken completely through. If a bone penetrates the skin, it is called an open or com-pound fracture (FIGURE 7-11). If not, it is called a closed or simple fracture. Fractures can also be described in terms of their location, their external appearance, and the manner in which the bone is broken:

■■ Comminuted fracture: This type is where the bone has fragmented into three or more pieces. This type is more common in elderly people, whose bones may be brittle.

■■ Compression fracture:The bone has been crushed. This type is common in porous bones such as when the condition known as osteopo-rosis exists or when a person falls from a great height, causing extreme bone trauma, an exam-ple is when vertebrae are subjected to extreme vertical stress.

■■ Depressed fracture: The broken bone portion is pressed inward, as often occurs in skull fractures.

■■ Epiphyseal fracture: The epiphysis has separated from the diaphysis along the epiphyseal plate. This type of fracture often occurs where cartilage cells are dying and the matrix is becoming calcified.

■■ Greenstick fracture: The bone breaks incompletely, with breakage occurring only on one side of the shaft, whereas the other side bends. This type of fracture is common in children, because their bones have more organic matrix, lending more flexibility than the bones of adults.

■■ Spiral fracture: Because of excessive twisting forces, a ragged bone break occurs. This type of fracture commonly occurs due to sports activities. Treatment of bone fractures requires reduction, which is the realignment of the broken bone ends. A closed or external reduction requires the physician to physically manipulate the bone ends into position. An open or internal reduction requires the bone ends to be pulled together surgically, using pins or wires. After reduction, the broken bones are immobilized by a cast or traction. In a young adult, a simple fracture of a small or medium-sized bone will heal within eight weeks. How-ever, the break of a larger, weight-bearing bone requires a much longer time to heal. In an elderly person, because of their reduced circulation, bone fractures always take longer to heal compared with younger adults. Various classifications of fractures are shown in FIGURE 7-12.

Bone Repair

For simple bone fractures, bone repair involves four primary stages (FIGURE 7-13): hematoma ­formation, formation of a fibrocartilaginous callus, formation of a bony callus, and the process of bone remodeling:

■■ Hematoma formation: The fracture of a bone causes bone and periosteum blood vessels to hemorrhage. A hematoma forms at the fracture site. This is also referred to as a fracture hematoma. Because of a lack of nutrients, bone cells die, and the area of the fracture becomes inflamed, painful, and swollen.

■■ Fibrocartilaginous callus formation: A soft fibrocartilaginous callus (soft granulation tissue) forms in a few days, with capillaries growing into the hematoma. This is also known as aninternal callus. Phagocytes engulf debris as fibroblasts, cartilage, and osteogenic cells begin bone reconstruction. Collagen fibers are produced by the fibroblasts, spanning the break and connecting the bone ends. Certain precursor cells differentiate into chondroblasts, secreting cartilage matrix. Inside the tissue repair mass, osteoblasts start to form spongy bone. Cartilage cells at the furthest point from the capillaries secrete a cartilaginous matrix, which bulges and eventually calcify. This entire repair tissue mass is called the fibrocartilaginous­ callus and splints broken bones.

■■ Bony callus formation: New bone trabeculae appear in the fibrocartilaginous callus within one week. They slowly convert it to a hard, bony callus of spongy bone. This is also known as an external callus. This process continues until a union has become firm and requires about two months. Basically,­ this process duplicates the events of endochondral ossification.

■■ Bone remodeling: The bony callus is remodeled during bony callus formation. This continues for several months. Excess material inside the med-ullary cavity and on the diaphysis is removed. Compact bone is laid down, rebuilding bone shaft walls. Eventually, the final repaired bone structure appears nearly identical to the original unbroken region, because it responds to the same forms of mechanical stress.

Bone Deposition

Areas of new bone matrix deposits are signified by oste-oid seams, unmineralized sections of thin bone matrix, only 10–12 μm in width. Between osteoid seams and older bone, an abrupt transition point exists, known as the calcification front. The osteoid seams mature for about one week before calcification occurs. Mechanical signals are involved in this calcification. In the endos-teal cavity, nearby concentrations of calcium and phos-phate ions are needed for calcification to occur. When this calcium–phosphate product is sufficient, tiny crystals of hydroxyapatites are formed. They catalyze continued crystallization of ­calcium salts. ­Additional factors include matrix proteins (which bind and con-centrate calcium) and alkaline phosphatase, an enzyme that is lost in matrix vesicles by osteoblasts, and which is critical for mineralization. Eventually, calcium salts are deposited at one time throughout the matured matrix in an ordered manner.

Bone Resorption

Bone resorption occurs because of osteoclast activ-ities, including the creation of grooves or depressions as bone matrix is broken down. Osteoclast borders use their irregular shape to stick to the bone and seal off areas of bone destruction. They secrete lysosomal enzymes, digesting protons and the organic matrix. In the resorption bays, the high acidity converts ­calcium salts into soluble forms. Dead osteocytes and deminer-alized matrix may be phagocytized by the osteoclasts. Endocytosis occurs to the digested growth factors, matrix end products, and dissolved minerals. These are moved, via transcytosis, across the osteoclasts to be released at the opposite end, entering the intersti-tial fluid and blood. Osteoclasts undergo ­apoptosis after a certain bone area has been resorbed. Both parathyroid­ hormone (PTH) and protein from the immune system’s­ T cells play a role.

Control of Bone Remodeling

Bone remodeling is controlled by genetic factors, a negative­ feedback hormonal loop, and in response to gravitational and mechanical forces. The ­negative feed-back hormonal loop maintains calcium ion homeo-stasis in the blood. Ionic calcium is essential­ for nerve impulse transmission, blood coagulation, ­muscle con-traction, cell division, and secretion by glands as well as nerve cells. More than 99% of the body’s 1,200–1,400 g of calcium is present in the bones. The remainder is primarily in the cells and a small amount is in the blood. Hormonal controls keep blood calcium ions in a range between 9 and 11 mg/dL (100 mL) of blood. Vitamin­ D metabolites control­ calcium absorp-tion from the intestine. ­Children under age 10 need 400–800 mg of ­calcium in their daily diet, whereas people between ages 11 and 24 require 1,200–1,500 mg.

Parathyroid Hormone

PTH is released by the parathyroid glands. It is the primary hormonal controller of bone remodeling, although calcitonin is also involved to a lesser degree, elevated levels of calcium ions in the blood stimulate the secretion of the hormone calcitonin. The parathy-roid glands are embedded in the thyroid gland in the neck. PTH is released when blood levels of ionic cal-cium decline, stimulating osteoclasts to resorb bone and releasing calcium into the blood. Osteoclasts break down old as well as new bone matrix. Rising blood calcium causes PTH release to stop, reversing its effects and lowering blood calcium. Blood calcium homeostasis is, therefore, maintained. However, if blood calcium levels are low for a long time, the bones lose minerals and develop large, irregular holes.

Both bone density and bone turnover react to a variety of hormones. The adipose tissue releases the hormone leptin, which helps to regulate bone density, weight, and energy balance. Leptin appears to inhibit the actions of osteoblasts, via mediation by the hypothal-amus, activating sympathetic nerves that serve bones. The balance between bone destruction and formation are regulated by interactive processes of the brain, skel-eton, and intestine. Serotonin mediates these processes and is primarily manufactured in the intestine­. It can-not enter the brain because of the blood–brain barrier. Serotonin is secreted during eating, circulating to the bones to interfere with osteoblast activity. Because bone turnover is reduced after eating, calcium may be held in bones while new calcium is moving into the blood-stream. Serotonin uptake inhibitors make excessive serotonin available to bone cells, resulting in lower bone density and higher potential for fracture.

Bone remodeling is also controlled by gravity and mechanical stressors. According to Wolff’s law, bones grow or remodel in response to demands placed on them. The anatomy of a bone is related to its com-mon stressors. A bone is stressed when muscles pull on it or weight bears down on it. These stressors are usually not centered and cause bending of the bone. On one side, the bone is compressed by bending, whereas on the other side, it experiences tension (stretching). Long bones are, therefore, thickest at the midpoint of the diaphysis because this is where bending stresses are strongest. Toward the center of the bone, compression and tension are lowest because of their opposition of each other’s effects. Without causing any serious complications, a bone can be hollowed out for lightness, which means using spongy bone rather than compact bone. Wolff’s law has several other points:

■■ Curved bones are thickest at the point where they are most likely to break.

■■ Whether you are right or left handed (handedness) determines the bones of the most-used upper limb to be thicker than those of the less-used upper limb. Large increases in bone strength occur from vigorous exercise of the most-used upper limb.

■■ Where heavy and active muscles attach, large and bony projections develop.

■■ Spongy bone trabeculae form a supportive frame work along compression lines.

■■ When bones are not stressed, such as in a fetus or an immobilized patient, the bones lack normal features. Deformation of a bone causes an electrical current, with compressed and stretched regions having oppo-site charges. Therefore, it is believed by some experts that electrical signals are in control of bone remodel-ing. Within the canaliculi, the flowing of fluids appears to provide stimuli that control bone remodeling.

Both hormonal and mechanical factors affect the skeleton continuously. Hormonal controls, in response to changing levels of blood calcium, deter-mine when (and if ) remodeling occurs. The location where remodeling occurs is determined by mechanical stressors. When bone is required to be broken down to increase blood calcium, PTH is released, targeting osteoclasts. Mechanical forces determine which of the osteoclasts will be most sensitive to PTH. Therefore, bone in areas of lowest stress is broken down because it is temporarily not essential to the body.

1. Describe the borders created by osteoclast activity and their significance.

2. For maintaining blood calcium levels needed for bone homeostasis, is PTH or mechanical stressors more important as a stimulus?

3. Differentiate between bone growth and bone remodeling.