Bone pathology lecture1

Babylon University Stage Fourth
College of Medicine Bone Pathology Lecture 1
Dr. Athraa Falah
Normal
Bone is a type of connective tissue, and it is unique because it is one of the few tissues that normally undergo mineralization. Biochemically, it is defined by its distinctive admixture of inorganic elements (65%) and organic matrix (35%).
The rate of mineralization can vary, but normally there is a 12- to 15-day lag time between the formation of the matrix and its mineralization. Bone that is unmineralized is known as osteoid.
Healthy bone is composed of hard, compact bone tissue and a spongy tissue with a strong honeycomb-like structure. Blood vessels transfer calcium and other nutrients to and from bone. Bone marrow fills cavities in larger bone.
The organic component includes the cells of bone and the proteins of the matrix. The bone-forming cells include the osteoprogenitor cells, osteoblasts, and osteocytes.
• Osteoprogenitor cells are pluripotent mesenchymal stem cells that are located in the vicinity of all bony surfaces. When stimulated by growth factors , they undergo cell division and produce offspring that differentiate into osteoblasts.
• Osteoblasts cells are located on the surface of bone and synthesize, transport, and arrange the many proteins of matrix . They also initiate the process of mineralization. Osteoblasts have a life span of approximately 3 months and then either undergo apoptosis, become surrounded by matrix and transform into osteocytes, or become quiescent, flattened, bone surface-lining cells.
• Osteocytes are more numerous than any other bone-forming cell. Although encased by bone, they communicate with each other and with surface cells via an intricate network of tunnels through the matrix known as canaliculi.

• The osteoclast is the cell responsible for bone resorption. It is derived from hematopoietic progenitor cells that also give rise to monocytes and macrophages. Mature multinucleated osteoclasts (containing 6 to 12 nuclei) form from fusion of circulating mononuclear precursors. They are intimately related to the bone surface, where their activity is initiated by binding to matrix adhesion proteins.
• The proteins of bone include type 1 collagen and a family of noncollagenous proteins that are derived mainly from osteoblasts.
Type 1 collagen forms the backbone of matrix and accounts for 90% of the weight of the organic component. Osteoblasts deposit collagen either in a random weave known as woven bone or in an orderly layered manner designated lamellar bone.
Normally, woven bone is seen in the fetal skeleton and is formed at growth plates. The presence of woven bone in the adult is always indicative of a pathologic state It is also formed around sites of infection and composes the matrix of bone-forming tumors.
Lamellar bone, which gradually replaces woven bone during growth, is deposited much more slowly and is stronger than woven bone.
Pathology
Diseases Associated with Decreased Bone Mass
Osteoporosis
-Osteoporosis is a disease characterized by increased porosity of the skeleton resulting from reduced bone mass.
-The associated structural changes predispose the bone to fracture.
-The disorder may be localized to a certain bone or region, as in disuse osteoporosis of a limb, or may involve the entire skeleton, as a manifestation of a metabolic bone disease.
-Generalized osteoporosis may be primary, or secondary to a large variety of conditions.
-The most common forms of osteoporosis are senile and postmenopausal osteoporosis. In these disorders, the critical loss of bone mass makes the skeleton vulnerable to fractures.
Pathogenesis.
Age-related bone loss, which may average 0.7% per year, is a normal and predictable biologic phenomenon. Both sexes are affected equally and whites more so than blacks.
Although the pathogenesis remains unknown, recent advances in elucidating the molecular biology of bone have provided new hypotheses in the pathogenesis of osteoporosis:
• Age-related changes(senile osteoporosis).
-Osteoblasts from elderly individuals have reduced replicative and biosynthetic potential when compared with osteoblasts from younger individuals.
-Also, proteins bound to the extracellular matrix lose their biologic potency over time.
• Reduced physical activity increases the rate of bone loss in experimental animals and humans because mechanical forces are important stimuli for normal bone remodeling such as that seen in an immobilized or paralyzed extremity.
• Genetic factors are also important.
-The type of vitamin D receptor molecule that is inherited accounts for approximately 75% of the maximal peak mass achieved.
-Calcium deficiency, increased PTH(parathyroid hormone) levels, and reduced levels of vitamin D also may play a role in the development of senile osteoporosis.
• The body s calcium nutritional state is important. It has been shown that adolescent girls (but not boys) have insufficient calcium intake in the diet. This calcium deficiency occurs during a period of rapid bone growth, stunting the peak bone mass ultimately achieved; thus, these individuals are at greater risk of developing osteoporosis.
• Hormonal influences. In the decade after menopause, yearly reductions in bone mass may reach up to 2% of cortical(copact) bone and 9% of cancellous(spongy) bone.
-Postmenopausal osteoporosis is characterized by a hormone-dependent acceleration of bone loss that occurs during the decade after menopause.
-Estrogen deficiency plays the major role in this phenomenon, and estrogen replacement at menopause is protective against bone loss.

Morphology.
In postmenopausal osteoporosis, the increase in osteoclast activity affects mainly bones or portions of bones that have increased surface area, such as the cancellous(spongy) compartment of vertebral bodies. The osteoporotic trabeculae are thinned and lose their interconnections, leading to progressive microfractures and eventual vertebral collapse.
In senile osteoporosis, the osteoporotic cortex is thinned by subperiosteal and endosteal resorption and the haversian systems are widened
Clinical Course.
The clinical manifestations depend on which bones are involved.
Vertebral fractures that frequently occur in the thoracic and lumbar regions are painful. Multi-level fractures can cause significant loss of height and various deformities, including lumbar lordosis and kyphoscoliosis.
Complications of overt fractures of the femoral neck, pelvis, or spine, such as pulmonary embolism and pneumonia, are frequent and result in 40,000 to 50,000 deaths per year.
The prevention and treatment of senile and postmenopausal osteoporosis include exercise, appropriate calcium and vitamin D intake, and pharmacologic agents, including estrogen replacing agents, bisphosphonates, and recombinant PTH.
Infections—Osteomyelitis
Pyogenic Osteomylitis
Pyogenic osteomyelitis is almost always caused by bacteria. Organisms may reach the bone by (1) hematogenous spread, (2) extension from a contiguous site, and (3) direct implantation. Most cases of osteomyelitis are hematogenous in origin and develop in the long bones or vertebral bodies in otherwise healthy individuals.
Staphylococcus aureus is responsible for 80% to 90% of the cases of pyogenic osteomyelitis in which an organism is recovered.
Morphology.
The morphologic changes in osteomyelitis depend on the stage (acute, subacute, or chronic) and location of the infection.
Once localized in bone, the bacteria proliferate and induce an acute inflammatory reaction and cause cell death. The entrapped bone undergoes necrosis within the first 48 hours, and the bacteria and inflammation spread within the shaft of the bone.
In children, sizable subperiosteal abscesses may form, which can trek for long distances along the bone surface. Lifting of the periosteum further impairs the blood supply to the affected region, and both suppurative and ischemic injury may cause segmental bone necrosis; the dead piece of bone is known as the sequestrum.
Rupture of the periosteum leads to an abscess in the surrounding soft tissue and the eventual formation of a draining sinus.
Over time, the host response develops, and after the first week of infection chronic inflammatory cells become more numerous. Reactive woven or lamellar bone may be deposited, and when it forms a sleeve of living tissue around a segment of devitalized bone, it is known as an involucrum.
Clinical Course.
Clinically, hematogenous osteomyelitis may manifest as an acute systemic illness with malaise, fever, chills, leukocytosis, and throbbing pain, often intense, over the affected region.
The presentation may be subtler with only unexplained fever, particularly in infants, or only localized pain in the absence of fever in the adult.
The combination of antibiotics and surgical drainage is usually curative. In 5% to 25% of cases, acute osteomyelitis fails to resolve and persists as chronic infection.