Bones and Joints

Chapter 20 Bones and Joints

Ivan Damjanov, MD, PhD

1 What are the main anatomic portions of tubular long bones?

The midportion of a tubular long bone is called the diaphysis. The articular portion of these bones is called epiphysis. The part of the bone between the epiphysis and the diaphysis is called the metaphysis. In growing bones of children and adolescents, the midportion of the metaphysis contains the physis or the cartilaginous growth plate. The calcifying growth plates, easily recognizable on x-ray, are called secondary ossification centers, in contrast to primary ossification centers, a term used for the subperiosteal cortical bone formation. See Fig. 20-1.

Figure 20-1 Anatomic parts of the long bone. The epiphyseal growth plate is seen only in growing bones, and it disappears after puberty.

2 Name the main bone-forming cells in the bone

Osteocytes: These mature resting cells are involved in the maintenance of the basic functional and anatomic units of the bone, called osteons. Osteocytes also participate in the maintenance of the blood concentration of calcium and phosphates.

Osteoblasts: These bone-forming cells synthesize osteoid and participate in its calcification. Osteoblasts can be stimulated by parathyroid hormone, vitamin D, and estrogens.

Osteoclasts: These bone-resorbing cells are closely related to macrophages. Thus they are derived from the same bone marrow precursors responding to granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor. In contrast to mononuclear macrophages, osteoclasts are multinucleated.

In addition to these cells, which are related to the formation, maintenance, and resorption of the bone matrix, bones contain other cells that can be found in anatomic sites, such as fibroblasts and blood vessels. The joint surface of the mature bone and the growth plate of the growing long bones contain cartilage cells. The bone marrow contains hematopoietic and fat cells.

3 What is the difference between lamellar and woven bone?

Newly formed bone, composed of haphazardly arranged strands of collagen, appears like woven cloth when examined microscopically under polarized light. Gradually, it transforms into lamellar bone, composed of parallel arrays of mineralized osteoid. Woven bone is formed in growing children, whereas lamellar bone, which is stronger and more resistant to stress, is a typical component of adult bones.

DEVELOPMENTAL ABNORMALITIES

5 What is adactyly?

A congenital abnormality characterized by an absence of fingers.

6 What is amelia?

A congenital abnormality characterized by an absence of upper or lower extremities or both.

7 Define arachnodactyly

Arachnodactyly (literally, “spiderlike fingers”) is a feature of Marfan syndrome. It can be found in other disorders involving genes that encode extracellular matrix proteins, such as Ehlers–Danlos syndrome. However, many legendary violinists, such as Paganini, and pianists, such as Rubinstein, had long fingers but were otherwise normal. Hence, long fingers are not necessarily stigmata of a congenital disorder.

8 What is syndactyly?

A congenital abnormality characterized by fusion of the fingers or the toes. It results from defective apoptosis of interdigital cells in the fetal limb buds.

9 Explain the pathogenesis of achondroplasia

An autosomal dominant form of congenital dwarfism caused by abnormal formation of the epiphysial growth plate of long tubular bones. The defect lies in the gene encoding the fibroblast growth factor receptor-3 (FGF-3), which plays a critical role in the growth of cartilage. In normal circumstances, FGF-3 inhibits the proliferation of cartilage cells, but this inhibition does not take place in people with a mutated receptor. These people have broad epiphysial growth plates composed of constantly proliferating cartilage cells that are not replaced by osteoblasts. Accordingly, tubular bones do not grow longitudinally. The affected person has short limbs, a normal trunk, and a relatively large head. Approximately 80% of all achondroplastic dwarfs have normal parents, and their disease is caused by a new mutation.

10 What is osteogenesis imperfecta (OI)?

Also known as “brittle bone disease,” OI is not a single disease. It occurs in four forms, all of which are related to the mutation of the genes encoding the chains of type I collagen. The defects in the synthesis of collagen type I cause osteopenia and make bones weak and fragile.

11 How does OI present?

Severe forms of OI, such as OI type II, may present with multiple fractures during fetal life and are usually fatal. Milder forms of OI may present with stunted growth and increased fragility of bones, predisposing affected people to fractures even after minimal injury.

12 What are the typical extraskeletal manifestations of osteogenesis imperfecta?

All tissues containing collagen type I, which is actually present in various amounts in most organs, may be affected. However, these defects remain mostly inapparent. Visible abnormalities include blue sclerae and dental defects. Hearing defects are common because of abnormalities in the middle and inner ear.

14 What is osteopetrosis?

Osteopetrosis, or marble bone disease, is a genetic disorder characterized by abnormal thickening of bones. It is related to some undefined defect in the function of osteoclasts, which do not resorb the bone. The bones grow but are not remodeled and ultimately obliterate the marrow spaces. Such bones are fragile and easily broken. Anemia caused by the compression of the hematopoietic bone marrow by sclerotic bone is common.

METABOLIC DISORDERS

15 Define osteopenia

Osteopenia (literally, “lack of bone”) is a radiologic term used to denote a decreased amount of bone visible on x-ray. It can be congenital or acquired and includes many pathologic entities, such as osteogenesis imperfecta, osteoporosis, and osteomalacia.

18 What are the risk factors for developing osteoporosis?

Age: Osteoporosis is an age-related disease, and its incidence increases with advanced years.

Genetic factors: Osteoporosis runs in families and is considered to be a multifactorial disease. People who have thin bones and a small skeleton are more likely to develop osteoporosis than those who have a large frame (peak bone mass).

Sex: Women are more susceptible to osteoporosis than men.

Hormones: Deficiency of estrogen in the postmenopausal period accelerates osteoporosis. Estrogen replacement therapy may retard the development of osteoporosis.

Nutritional status: Calcium and vitamin D are essential for the maintenance of the skeleton, and a deficiency of these nutrients promotes osteoporosis.

Physical activity: Reduced physical activity promotes osteoporosis.

Environmental factors: Cigarette smoking and alcohol abuse promote osteoporosis.

19 Is primary osteoporosis a single entity?

Primary osteoporosis is not a single pathologic entity. Two distinct types of primary osteoporosis are recognized:

Type 1 primary osteoporosis typically occurs in postmenopausal women. It is caused by increased activity of osteoclasts, related to decreased levels of estrogen in the circulation. Lack of estrogen is associated with an increased release of cytokines, such as interleukin (IL)-1 and IL-6, which stimulate osteoclasts.

Type 2 primary osteoporosis, known as senile osteoporosis, affects both men and women. The pathogenesis of loss is not understood. Bone loss in this form of bone atrophy is not related to an increased osteoclastic activity, and the cause of bone loss is obscure.

20 Which bones are affected most by osteoporosis?

Type 1 (postmenopausal) osteoporosis primarily affects bones that have a large cancellous compartment, such as vertebral bodies. Compression fractures of vertebral bodies are thus common in this condition.

Type 2 (senile) osteoporosis leads to thinning of the cortical portion of long bones, which become fragile. Stress fractures of weight-carrying bones, especially the femur, are common in this form of osteoporosis.

21 How is osteoporosis diagnosed clinically?

In most instances, osteoporosis is asymptomatic, and the diagnosis of this disease is usually made accidentally during a workup for another disease or following bone fracture. Radiologists can recognize osteopenia after the bone loss exceeds more than 30% to 40% of the total bone mass. Osteopenia does not necessarily mean that the bone loss is due to osteoporosis; osteomalacia can also produce the same radiologic changes. Accordingly, to document osteoporosis one must use additional methods developed to measure bone density. Such techniques (e.g., single-energy photon absorptiometry) are rarely used except in research studies in highly specialized centers.

22 Does osteoporosis cause biochemical abnormalities that can be detected in the clinical laboratory?

The typical laboratory tests used for assessing bone diseases give normal results in osteoporosis. Accordingly, one can expect that serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase will be within normal limits.

23 Can osteoporosis be diagnosed histologically by bone biopsy?

Bone biopsy is diagnostic in advanced osteoporosis. In such cases, the bone spicules are thinner than normal because of an even loss of mineral and nonmineral (osteoid) components of the bone. Unfortunately, given the great variation in the appearance of normal bone spicules, mild osteoporosis cannot be detected so easily.

24 What is osteomalacia?

Osteomalacia (literally, “softening of bones”) is a metabolic disorder characterized by inadequate mineralization of osteoid. Osteomalacia of growing children is called rickets.

26 Discuss the histologic features of osteomalacia

In osteomalacia, the bone trabeculae are of normal thickness, but they are incompletely calcified. The central core of these bone spicules is normally calcified, but their peripheral portion is composed of uncalcified osteoid. These seams of uncalcified osteoid are lined by numerous osteoblasts.

27 What are the typical clinical laboratory findings in osteomalacia?

Vitamin D deficiency is associated initially with low blood levels of calcium and phosphate and a normal level of parathyroid hormone (PTH). PTH elevation that occurs subsequently may raise the blood levels of phosphate. Increased activity of osteoblasts is associated with an elevation of blood alkaline phosphatase.

28 What are the clinical features of osteomalacia?

Clinical symptoms of osteomalacia are nonspecific and usually include vague deep skeletal pain, gradual deformity of weight-carrying bones (e.g., deformity of femur and tibia), and a predisposition to fractures. X-rays show osteopenia and radiolucent bands (pseudofractures or Looser’s zones). Vertebral bodies are typically biconcave because of the central compression of softened vertebrae by intervertebral disks. In contrast to osteoporosis, which is irreversible, the changes of osteomalacia can be reversed by supplementing the diet with adequate amounts of vitamin D and by normalizing the metabolism of calcium.

29 How does hyperparathyroidism affect the bones?

Hyperparathyroidism is associated with increased bone resorption and replacement of bone trabeculae with fibrous tissue. Histologically, the affected bones contain increased numbers of osteoclasts. These multinucleated cells are most prominent inside the lacunae (i.e., invaginations of the bone trabeculae undergoing resorption). The weakened trabeculae fracture and cause bleeding. The fibrous tissue replacing the bone will therefore contain not only fibroblasts but also hemosiderin-laden macrophages.

30 Are the bone lesions of hyperparathyroidism localized or diffuse?

Although the parathyroid hormone affects the entire skeleton, some bones react more prominently than others. The skeletal changes are thus diffuse, but locally they may present in the form of tumoral swelling and cystic bone destruction. Three pathologic lesions are typically recognized:

Osteitis fibrosa: Fibrous tissue replacing bone trabeculae in numerous bones or the entire skeleton.

Osteitis fibrosa cystica (von Recklinghausen disease): Cystic lesions caused by extensive resorption of cortical bone and subsequent cystic expansion of the bone defect.

Brown tumor of hyperparathyroidism: Expansile, tumorlike proliferations of osteoclasts, resembling neoplastic giant cell tumors of bones. Because of early diagnosis and better treatment of hyperparathyroidism, brown tumors are rare today.

31 Where are the changes caused by hyperparathyroidism best recognized?

Hyperparathyroidism leads to the resorption of cortical bone, which is more affected than the cancellous bone. The most typical changes are seen in the middle phalanges of the index and middle fingers.

32 What is renal osteodystrophy?

The term renal osteodystrophy is used to describe a set of changes seen in the bones of patients suffering from chronic renal insufficiency. It is not a unique pathologic entity, and the diagnosis is usually made only by correlating the clinical, x-ray, laboratory, and pathologic findings.

33 What are the pathologic features of renal osteodystrophy?

In most instances, the bone changes are a combination of those seen in osteomalacia and hyperparathyroidism. In a dynamic renal osteodystrophy, there is also osteoporosis. Some cases show marked osteosclerosis alternating with osteoporosis, a pattern described by British radiologists as “rugger (rugby) jersey spine.”

34 Why do patients on chronic renal dialysis have bone disease?

Patients on chronic renal dialysis show deposition of aluminum and iron in the bones. Aluminum, derived from dialysis solutions, inhibits mineralization of osteoid and contributes to osteomalacia. Deposits of amyloid derived from b2 microglobulin are also found in such patients.

35 What is Paget disease of bone?

Paget disease of bone (also known as osteitis deformans) is a disease of unknown etiology, characterized by abnormal remodeling and thickening of bones. Viral particles have been found in the bone cells on electron microscopy, but the significance of this finding is unknown.

36 How common is Paget disease?

Approximately 1% of all Caucasian men older than 50 years have some signs of Paget disease; however, the condition is rare in other races. The importance of Paget disease lies in the fact that it is one of the predisposing factors for bone sarcoma in adults.

38 What are the clinical features of Paget disease?

Paget disease is usually asymptomatic and is incidentally discovered as thickening of bones during routine radiologic examinations or following unexplained elevation of alkaline phosphatase in the blood. The disease may be monostotic or polyostotic. Thickened bone may cause enlargement of the head (e.g., hats do not fit anymore), deafness or visual disturbances (because of the compression of cranial nerves), or sciatica (due to compression of lumbar nerve roots). Although the bones are thick, they are brittle and prone to fractures (chalkstick fractures). Bow leg deformities are common. Most of the laboratory findings (including serum calcium, phosphate, and parathyroid hormone) are within normal limits, but the blood alkaline phosphatase levels are elevated. The urine may contain increased amounts of calcium in the osteolytic phase of the disease.

Osteogenic sarcomas develop at an increased rate in patients suffering from Paget disease. In the polyostotic form of Paget disease, these tumors may be multifocal.

39 Describe how clinical laboratory data help in the diagnosis of metabolic bone diseases

The clinical laboratory has an invaluable role in the study of bone diseases that present radiologically as osteopenia or osteopenia combined with osteosclerosis. The complete workup of the patient will typically require information on the serum calcium, phosphate, and alkaline phosphatase, which then can be supplemented with more expensive tests, such as measurement of PTH and vitamin D in blood. Typical findings are listed in Table 20-1.

TABLE 20-1 Laboratory Findings in Metabolic Bone Diseases

FRACTURES

40 Are all fractures caused by trauma?

Most, but not all, fractures are caused by obvious trauma incurred through a fall or extraneous force. Fractures related to repeated minor or inapparent trauma (e.g., prolonged march and sports injuries) are called stress fractures. Fractures that occur in pathologically altered bones, during normal activity and seemingly unrelated to trauma, are called pathologic fractures.

41 List three examples of pathologic fractures

Fracture of the femur invaded by tumor

Fracture of leg bones in Paget disease

Compression fracture of vertebrae in osteoporosis

42 What is the difference between complete and incomplete fractures?

Complete fractures result in bone fragments that are separated from each other. Comminuted fracture is a complete fracture in which the bone is broken into numerous fragments. Displaced fracture denotes that the fractured bone parts have moved out of alignment. In incomplete fractures, the continuity of bones is not disrupted. These are also called greenstick fractures. Spiral fracture of the long bones is another form of incomplete fracture.

43 What is the difference between closed and open fractures?

Closed (simple) fracture: The overlying soft tissue and skin are intact.

Open (compound) fracture: The gaping fracture site communicates with the outside world and is typically infected.

44 What is callus?

Callus is the Latin name for the hardening of the skin, such as on feet constantly traumatized by tight shoes. The same term is used in bone pathology for the hardening of the connective tissue that fills the gap between two bone fragments at the site of fracture.

45 How do bone fractures heal?

The healing of bone fractures is a continuous process that can be divided into three stages:

Provisional callus (procallus): It forms during the first week after fracture and is composed of granulation tissue, newly formed cartilage, and osteoid. It is typically fusiform, filling the defect caused by fracture, but also bulging over the edges of the fractured bone fragments.

Fibrocartilaginous callus: Formed during the second week from the procallus, it consists of more abundant collagenous matrix, cartilage, and osteoid that is in the process of calcification.

Fibroosseous callus: It is composed of haphazardly arranged bone spicules surrounded by connective tissue. Over time, the bone spicules are reformed and realigned to correspond to preexisting bone lost by fracture.

46 What is osteonecrosis?

Osteonecrosis is a clinical term used for localized death of bone due to infarcts. Thus, this lesion is also called avascular necrosis: To emphasize that these lesions are not caused by infection, they are also called aseptic necrosis.

Foci of osteonecrosis can be found in many locations and may be solitary or multiple. Depending on their anatomic location, they can be classified as:

Medullary: It involves the bone marrow and internal cancellous bone of long and short bones.

Cortical: It involves the subchondral or subperiosteal cortex of long bones.

47 What are the main causes of osteonecrosis?

Although it is assumed that osteonecrosis results from ischemia, its true cause is not evident in most cases, and in such instances the disease is considered to be idiopathic. For example, it is not known why chronic alcoholics often develop osteonecrosis of the head of the femur. Idiopathic osteonecrosis necessitates approximately 50,000 femoral head replacements annually in the United States.

Idiopathic osteonecroses in children and adolescents often have clinical eponyms. For example, osteonecrosis of the head of the femur, typically found in 3- to 10-year-old boys, is known as Legg–Calvé–Perthes disease. Osteonecrosis of the epiphysial tubercle of the tibia is known as Osgood–Schlatter disease.

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Jul 23, 2016 | Posted by admin in PATHOLOGY & LABORATORY MEDICINE | Comments Off

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