A failure of endochondral bone growth, usually caused by a Mendelian dominant defect, that results in shortened extremities. A mutation of the FGF-3 receptor is often involved inpathogenesis.
Achondroplasia
An enzyme that hydrolyses phosphate
esters, is secreted into the serum by osteoblasts and is used as a diagnostic marker for increased osteoblastic metabolic activity.
Alkaline phosphatase
An inflammatory, RA-like arthritis, of the spine and sacro-iliac joints, which is seronegative for rheumatoid factor. It is most common in young men in their 20s and is strongly associated with HLA-B27 antigen.
Ankylosing spondylitis
Firm fixation of a joint due to fusion of the bones.
Ankylosis
A type of crystal deposition disease in which crystals of hydroxyapatite are deposited in articular cartilage and joint capsule. Release of the crystals into the joint spacecauses severe acute arthritis. Milwaukee shoulder is a variant of apatite deposition arthritis occurring in a previously traumatized and torn rotator cuff of the shoulder.
Apatite-associated crystal deposition arthritis
Bone infarcts resulting from occlusion of small vessels, usually at the ends of the long bones, produce multiple subarticular bone defects. Pathogenesis Nitrogen embolization in divers with caisson disease, fat emboli, in transplant and other patients on steroids for immunosuppression, idiopathic in Perthe disease (avascular necrosis of the femoral head), and osteochondritis dessicans (subarticular infarcts in a variety of weight-bearing bones).
Avascular (aseptic) necrosis of bone
An arthritis of unknown etiology resulting from excessive deposition of calcium pyrophosphate dihydrate crystals bilaterally within the midzone of articular cartilage of weight-bearing joints. This condition is common in the elderly, but is usually asymptomatic and discovered as an incidental finding on x-ray. An inflammatory arthritis may occur when calcium pyrophosphate crystals are released into the joint space where they provoke an inflammatory reaction.
Calcium phosphate deposition disease (CPDD, pseudogout or chondrocalcinosis)
New growth of incompletely organized bony tissue surrounding and uniting the broken ends of bone at a
fracture site.
Callus
The second most common primary malignant tumor of bone. It occurs most often in adults age 40 to 60, often in the medullary cavity of pelvis, ribs or long bones, and is cartilaginous.
Chondrosarcoma
The type of collagen that predominates in
cartilage matrix
Type II
The mid-portion or shaft of a long bone. It is composed of an outer dense cortex and an inner medullary region
containing bone spicules and interspersed marrow.
Diaphysis
The wearing away of articular cartilage to yield
a hard, bony articulating surface.
Eburnation
Benign, cartilaginous neoplasm usually arising within the medullary cavity of bone. It is usually solitary, most common from ages 20 to 50, and most often seen in the small bones of the hand or foot. Ollier multiple enchondromatosis is a rare, non-hereditary form of this disease.
Enchondroma
Process of bone formation at cartilaginous epiphyseal growth plates.
Endochondral ossification
A region of bone, located at the ends of long bones, composed of cartilage in embryonic life, but subsequently becoming osseous with the closure of the growth plates after adolescence.
Epiphysis
A highly malignant, destructive bone tumor of childhood, arising more often in the medullary space of the diaphysis of long bones. The tumor is composed of small, poorly differentiated round cells with highly glycogenated cytoplasm, possibly of neuroectodermal origin. An 11:22 chromosomal translocation is often present.
Ewing sarcoma
Rheumatoid arthritis plus splenomegaly and leukopenia.
Felty syndrome
The formation of crevices and cracks in the articular cartilage in osteoarthritis.
Fibrillation
Rapidly enlarging, radiolucent tumor of young adults, ages 30-40, most often arising at the junction of epiphysis and metaphysis in long bones. The tumor giant cells are derived from osteoclast precursor cells.
Giant cell tumor of bone
A disorder of uric acid metabolism characterized by hyperuricemia, with resulting deposits of urates in joints, kidneys and soft tissues. The disorder is characterized by recurrent bouts of acute arthritis, usually in the lower extremities.
Gout
Fusiform enlargement of distal interphalangeal joints due to osteophyte formation in osteoarthritis. These painful nodular enlargements are seen mostly in women, in a familial pattern.
Hebreden nodes
A complex crystal of calcium phosphate, (Ca)10 (P04)6(OH)2. Bone and cartilage mineral is composed almost exclusively of hydroxyapatite.
Hydroxyapatite
Periosteal inflammation and fibrosis leading to enlargement and clubbing of the distal phalanges. The etiology of this condition is unknown. It is usually associated with intrathoracic neoplasms such as bronchogenic carcinoma, thymoma or mesothelioma.
Hypertrophic osteoarthropathy
A broken and dislodged osteophyte that becomes a movable body in the joint space. With time, the dislodged bone fragment becomes coated with a layer of regenerative cartilage.
Joint mouse
A systemic disease, due to spirochetal infection by Borrelia burgdorferi, characterized by a RA-like arthritis, first identified in adults and children living in a wooded village of Connecticut (Lyme) near the Connecticut river. Clinically dangerous features of Lyme disease include myocarditis, cardiac arrhythmias and encephalitis.
Lyme disease
A solitary malignant neoplasm of variable histology, composed primarily of fibroblastic cells arranged in a storiform (cartwheel) pattern, with interspersed, foamy histiocyte-like cells. The tumor occurs in a wide range of ages (10 to 80) and locations, more commonly arising in the metaphyses of long bones, but can arise in any site.
Malignant fibrous histiocytoma (MFH)
A region of rapidly growing trabecular bone underlying the base of the cartilaginous growth plate.
Metaphysis
A slowly progressive condition of unknown etiology, seen in almost everyone after the age of 50, and characterized by degeneration and thinning of articular cartilage surfaces, associated with the formation of bone spurs (osteophytes) at the articular margins.
Osteoarthritis (degenerative joint disease)
The most common benign tumor of bone, appears as a cartilage-capped lateral bony projection from the metaphysis, just below the growth plate, also known as an exostosis.
Osteochondroma
A hereditary defect in collagen type I synthesis causes deficient intramembranous and cortical bone formation.The result is fragile bones with frequent fractures and progressively worsening deformity of the weight-bearing bones.
Osteogenesis imperfecta
Precalcified bone matrix composed mostly of type I collagen
Osteoid
Small, solitary, painful cortical lesion with radiolucent central nidus surrounded by a sclerotic, hyperdense
zone of reactive bone formation.
Osteoid osteoma
Adult onset rickets. A failure of calcification resulting from inadequate serum levels of calcium or phosphate or
both occurs after the closure of the growth plates.
Osteomalacia
A chronic progressive bacterial infection localizing in bone with subsequent purulent inflammation, localized bone necrosis (sequestrum), reactive periosteal bone growth (involucrum), and deformity due to unilateral unbalanced inhibition of bone growth.
Osteomyelitis
A hereditary abnormality of osteoclasts causes defective bone resorption and a failure of bone remodeling. The result is bones that are excessively dense on x-ray due to unopposed osteoblastic activity. These bones become hard (like marble), but are brittle and more often fractured than are normal bones.
Osteopetrosis (marble bone disease)
A diffuse reduction of bone mass and x-ray density, more often occurring in post-menopausal females. This is the most common metabolic disease in the world and is the underlying cause of 350,000 vertebral and hip fractures annually in the U.S., costing an estimated 1billion dollars. Pathogenesis: bone resorption exceeds bone formation to a mild degree over a long period leading to osteopenia. There is no defect in the mechanism of bone mineralization, but instead there is a decrease in number and size of mineralized bone trabeculae.
Osteoporosis
The most common primary malignant tumor of bone; peak incidence is at age 10 to 20 (except for osteosarcoma secondary to Paget disease which occurs in the 60s to 70s). This is an x-ray-dense tumor arising in the metaphysis that invades through the cortex, causing elevation of the adjacent periosteum (Codman triangle).
Osteosarcoma
A disease of the elderly in which repeated episodes of bone resorption are closely followed by excessive and disorderly bone formation resulting in a deformed skeleton with increased bone mass.
Paget disease of bone (osteitis deformans)
An inflammatory, hypertrophic synovial projection in rheumatoid arthritis that migrates from the joint capsule out over the articular surfaces causing chondrolysis of the underlying articular cartilage.
Pannus
A destructive form of tuberculous arthritis that most frequently involves the spine.
Potts disease
Is gout of idiopathic origin, most often in males in a familial pattern, due to over-synthesis of uric acid from
purine nucleotides.
Primary gout
(Formerly referred to as acid mucopolysaccharide), this is the predominant, non-collagenous component of cartilage matrix. Proteoglycans are large molecules with a central protein core and attached polysaccharide molecules extending from the protein core as do bristles in a bottle brush.
Proteoglycan
Combined urethritis, polyarthritis and conjunctivitis of unknown etiology; associated with HLA-B27 antigen in up to 90% of patients. The condition usually follows a venereal exposure and is almost exclusively seen in males.
Reiter syndrome
The final phase in healing of a fracture site in which the dead original bone ends and inefficiently placed spicules of callus are resorbed and replaced by osteoblastic action. The final result is new lamellar bone well-oriented to withstand mechanical forces across the fracture site.
Remodeling
A systemic, autoimmune inflammatory disorder affecting primarily multiple small joints of the hands and feet with production of synovitis followed by destructive changes in the articular cartilage. Females are affected three times more commonly than males. Onset is usually in the 30s to 40s.
Rheumatoid arthritis (RA)
An immune complex found in serum and synovial
fluid of patients with RA, composed of immunoglobulin autoantibodies directed against and complexed with normal serum IgG. The titer of serum rheumatoid factor correlates directly with the severity of RA
Rheumatoid factor
A subcutaneous nodule, seen in RA, usually periarticular in location, and composed of a central zone of zone of fibrinoid necrosis surrounded by palisading histiocyte and fibroblasts.
Rheumatoid nodule
A failure of the calcification process in bone and cartilage seen in children and adolescents with functioning growth plates.
Rickets
A condition of hyperuricemia due to excessive synthesis and catabolism of purines by neoplasms with rapid cell
turnover, as occurs in acute Leukemias
Secondary gout
Usually monarticular, involving one of the large joints and is most often caused by staphylococci, streptococci, pneumococci, gonococci or tuberculous organisms. In young adults, the gonococcus predominates. Typically, the affected joint is painful, shows redness and swelling and contains purulent synovial fluid.
Septic (suppurative) arthritis
RA associated with salivary gland enlargement and dryness of the eyes and mouth. The salivary glands are
infiltrated with lymphocytes.
Sjoren Syndrome
RA in children. Rheumatoid factor is often absent.
Still disease
Overriding dislocation of articulating bone ends
Subluxation
A 30-year-old man with dwarfism is admitted to the hospital for hip replacement due to severeosteoarthritis. He has short arms and legs and a relatively large head. His parents do not showsigns of this congenital disease. This patient most likely has a spontaneous mutation in the geneencoding which of the following proteins?
(B) Fibroblast growth factor receptor
A 2-year-old boy is treated for recurrent fractures of his long bones. Physical examinationreveals blue sclerae, loose joints, abnormal teeth, and poor hearing. Molecular diagnostic studieswill most likely demonstrate a mutation in the gene encoding which of the following proteins?
(C) Collagen
A 9-year-old boy is evaluated for signs of precocious puberty. Laboratory tests demonstrate a21-hydroxylase deficiency and increased serum levels of androgens. A CT scan revealsenlargement of the adrenal glands bilaterally. If this patient is untreated, short stature will resultas a consequence of which of the following mechanisms of disease?
(B) Premature epiphyseal plate closure
A 17-year-old girl suffers a spiral fracture of her right tibia, and the leg is casted.Unfortunately, the fracture does not heal correctly due to excessive motion and interposition ofsoft tissue at the fracture site. Which of the following represents the most likely complication ofnonunion in this patient?
(E) Pseudoarthrosis = non-unions
(X) A 50-year-old woman presents with lower back pain of 3 weeks in duration. Radiologicstudies reveal several discrete lytic lesions in the lumbar back and pelvis. Laboratory studiesshow elevated serum levels of alkaline phosphatase. Serum calcium, serum protein, andperipheral blood smears are normal. Aspiration biopsy of a pelvic lesion shows keratin-positivecells. Which of the following is the most likely diagnosis?
(B) Metastatic carcinoma
A 6-year-old child with mild hydrocephalus suffers chronic infections and dies of intractablechronic anemia. At autopsy, his bones are dense and misshapen. The femur in particular showsobliteration of the marrow space. Histologically, the bones demonstrate disorganization of bonytrabeculae by retention of primary spongiosa and further obliteration of the marrow spaces bysecondary spongiosa (shown). Hematopoietic bone marrow cells are sparse. The disorder is caused by mutations in genes that regulate which of the following cell types?
(E) Osteoclasts
A 33-year-old woman presents with a spontaneous fracture of her femoral head. She hassuffered from Crohn disease for 20 years. Multiple surgical procedures have resulted in removalof much of her small bowel. She has had profound weight loss over the last 10 years. The bone ispinned. Histologically, the resected femoral head shows bony trabeculae that are covered by athicker than normal layer of osteoid (shown). In this section, the osteoid is stained red, andmineralized bone is stained black. Which of the following best describes the pathogenesis of this lesion?
(B) Impaired mineralization of osteoid
An 18-year-old man presents with bone pain about his knee that he has had for 6 weeks.Radiologic studies reveal a lytic lesion of the distal end of the femur, which arises in themetaphysis, extends into the proximal diaphysis, and elevates the periosteum. Serum levels ofalkaline phosphatase are markedly elevated. The lesion is removed, and the cut surface of thesurgical specimen is shown. Molecular studies of this tumor would most likely reveal a mutationin the gene encoding which of the following proteins?
(C) Rb tumor suppressor protein
A 10-year-old boy complains of increasing pain in his left hip. He began limping shortly afterplaying a baseball game at school. He is afebrile. An x-ray of the femoral head shows a fractureand irregular densities of the cancellous bone. You make a diagnosis of Legg-Calvé-Perthesdisease. Which of the following best describes the pathologic findings in this patient?
(D) Avascular osteonecrosis
A 50-year-old man presents with a 2-day history of left leg pain. His temperature is 38.7°C(103°F). He has a harsh systolic murmur and echocardiographic evidence of bacterialendocarditis. If this patient has developed hematogenous osteomyelitis, his bone infectionwould most likely be found in which of the following anatomic locations?
(B) Metaphysis of a long bone
A 74-year-old, obese woman (BMI = 33 kg/m2) complains of chronic pain in her back, knees,and fingers. The pain typically subsides at rest. On physical examination, the distalinterphalangeal joints are enlarged and tender. Which of the following best describes thepathogenesis of joint pain in this patient?
(D) Degeneration of articular cartilage
A 60-year-old woman with arthritis suffers a massive stroke and expires. At autopsy, theproximal phalangeal joint tissue shows pannus, synovial cell hyperplasia, and lymphoid follicles.Which of the following best describes the pathogenesis of pannus formation in this patient?
(A) Chronic inflammation of synovium
A 9-year-old boy complains of 2 weeks of pain in the hip. His temperature is 38°C (101°F).Laboratory studies show an elevated erythrocyte sedimentation rate. An x-ray reveals a mottledradiolucent defect in the upper femur, with abundant periosteal new bone formation. Fine-needleaspiration returns numerous neutrophils and cocci. Staphylococcus aureus is cultured from thebone lesion. A biopsy shows a fragment of necrotic bone embedded in fibrinopurulent exudate.Which of the following terms best describes the necrotic bone?
(A) Sequestrum
A 40-year-old woman complains of morning stiffness in her hands. On physical examination,her finger joints are painful, swollen, and warm. X-ray examination of the hands shows narrowing of the joint spaces and erosion of joint surfaces of the metacarpal/phalangeal joints.The adjacent bones show osteoporosis. A synovial biopsy is shown. Laboratory studies conducted on a blood sample from this patient will most likely show polyclonal antibodiesdirected against which of the following proteins?
(E) Fc portion of IgG
A 55-year-old man presents with pain in the left arm. Laboratory studies show elevatedserum levels of calcium and parathyroid hormone. An x-ray of the left arm reveals multiple smallbone cysts and pathologic fractures. Biopsy of the affected bone discloses numerous giant cellsin a cellular and fibrous stroma. The patient undergoes removal of a parathyroid adenoma.Which of the following best describes the pathogenesis of bone pain and pathologic fractures inthis patient?
(E) Increased bone resorption
A 67-year-old man from England develops bow-legs and leg pain over a period of 5 years.He also complains of progressive hearing loss over the last 2 years. A bone biopsy shows amosaic pattern with prominent cement lines and increased osteoblastic and osteoclastic activity.Serum electrolyte levels are normal. This patient is at increased risk for developing which of thefollowing diseases?
(C) Osteogenic sarcoma (Paget's disease)
A 60-year-old man with a history of gout presents with multiple rubbery nodules on hishands (shown). Which of the following best explains the pathogenesis of this patient's underlyingcondition?
(B) Impaired renal excretion of uric acid
A 23-year-old man complains of stiffness and pain in his lower back that causes him toawaken at night. He first noticed morning stiffness in his lower back during his college years. Healso describes occasional pain in his right eye and sensitivity to light. An x-ray of the sacroiliacregion shows fusion of the small joint spaces in the posterior spine and ossification of theintervertebral discs. Serologic tests for rheumatoid factor and antinuclear antibodies are negative.This patient most likely expresses which of the following human leukocyte antigen (HLA)haplotypes?
(D) B27
A 28-year-old man complains of burning pain on urination, as well as pain in his fingers andleft eye. He also relates a recent episode of bacillary diarrhea contracted during a visit to Mexico.Physical examination confirms arthritis and conjunctivitis. The patient responds well to treatmentwith NSAIDs. Which of the following is the most likely diagnosis?
(E) Reiter syndrome p566
An 85-year-old man presents with a 3-week history of painful swelling of his right knee.Aspiration of joint fluid returns numerous neutrophils and crystals, which are described asrhomboid and “coffin-like.” Chemical analysis shows that these crystals are composed ofcalcium pyrophosphate. Which of the following is the most likely diagnosis?
(C) Pseudogout
A 10-year-old boy complains of pain in his hands and feet. His temperature is 38°C (101°F).Physical examination reveals a faint pericardial friction rub. His spleen, liver, and axillary lymphnodes are enlarged. Which of the following is the most likely diagnosis?
(A) Juvenile arthritis (Still diease)
A 58-year-old woman fractures her hip after slipping on an icy sidewalk. An x-ray showsgeneralized osteopenia. Bone biopsy reveals attenuated bony trabeculae and a normal ratio ofmineral-to-matrix. Serum calcium and phosphorus levels are normal. Which of the following best explains the pathogenesis of osteopenia in this postmenopausal woman?
(A) Increased osteoclast activity
A 16-year-old boy presents with a swelling on his left tibia. An x-ray of the leg shows adestructive process, with indistinct borders and an “onion-skin” pattern of periosteal bone.Histologic examination of a biopsy reveals uniform small cells with round, dark blue nuclei(shown). A PAS stain demonstrates abundant intracellular glycogen. Immunohistochemistry forleukocyte common antigen is negative. Which of the following is the most likely chromosomal abnormality in this tumor?
(B) t(11;22)
(X) A 2-year-old boy presents with a rash. On physical examination, he has a crusty, red skinlesion at the hairline and on the extensor surfaces of his extremities and abdomen. Exophthalmosis noted. An x-ray film of the head shows multiple, radiolucent lesions in the skull. A biopsy ofone of the skull lesions shows large, plump cells with pale, eosinophilic, foamy cytoplasm andconvoluted nuclei (shown). What is the most likely diagnosis?
(A) Ewing sarcoma
(B) Giant-cell tumor of bone
(C) Hand-Schüller-Christian disease
(D) Large B-cell lymphoma
(E) Multiple myeloma
A 17-year-old boy fractures his left tibia in a skiing accident. One year later, an x-ray of theleg discloses reactive bone formation in the calf muscle at the site of injury. Which of thefollowing is the most likely diagnosis?
(A) Myositis ossificans
A 16-year-old boy presents with a 2-week history of pain in his right leg. He says that he hasbeen taking aspirin to relieve the pain. An x-ray of the leg shows a 1-cm sharply demarcated,radiolucent lesion in the diaphysis of the tibia surrounded by dense, sclerotic bone. The lesion issurgically removed, and the gross specimen is shown. Microscopically, the tumor shows irregular trabeculae of woven bone surrounded by osteoblasts, osteoclasts, and fibrovascular marrow. What is the appropriate diagnosis?
(A) Chondroblastoma
(B) Giant-cell tumor of bone
(C) Osteoblastoma
(D) Osteoid osteoma
(E) Solitary chondroma
D) Osteoid osteoma
A 68-year-old woman presents with a lump in the soft tissue of her neck. Physicalexamination reveals a 0.5-cm subcutaneous tumor. Biopsy of the mass shows a benign neoplasm.The patient is told that she has the most common soft tissue tumor. What is the appropriatediagnosis?
(D) Lipoma
(X) A 56-year-old woman receives high-dose radiation therapy for thyroid carcinoma. One yearlater, the patient presents with a subcutaneous mass at the site of irradiation. A photomicrographof the biopsy is shown. Which of the following is the most likely diagnosis?
(X) A 40-year-old woman presents with pain and swelling in her left elbow that has lasted 6months. Physical examination reveals a 0.5-cm soft tissue mass. Biopsy of the mass discloses abiphasic histologic pattern consisting of cuboidal epithelial and spindle-shaped mesenchymalcells. Which of the following is the most likely diagnosis?
A 50-year-old man complains of fever and severe pain in his great toe of 24 hours induration. The pain developed in the morning and became so severe that he could not walk.Laboratory findings include leukocytosis, hyperuricemia, and hyperlipidemia. An x-ray of theaffected joint reveals punched-out lesions in the juxta-articular bone. An aspirate of joint fluidreturns urate crystals and neutrophils. Which of the following would be the most likelypathologic finding within the periarticular soft tissue of this patient?
(E) Tophus
A 35-year-old woman has multiple cartilaginous lesions in her long and short bones. Aradiograph of the hand (shown) reveals bulbous swellings. A biopsy shows abnormally arrangedhyaline cartilage, with scattered zones of proliferation. This patient is at risk for which of thefollowing bone diseases?
(D) Osteosarcoma
A 24-year-old man on chronic steroid therapy for severe asthma presents with a 6-monthhistory of increasing hip pain. This patient most likely exhibits symptoms of which of thefollowing metabolic bone diseases?
