Pathology of the musculoskeletal system

Question 1

Classification of primary osteoporosis

Answer 1

• Senile

- Postmenopausal: due to decreased estrogen

Question 2

Etiology of secondary osteoporosis

Answer 2

• Endocrine disorders: hyperparathyroidism, hypo/hyperthyroidism, hypogonadism, pituitary tumors
• GI disorders: malnutrition, malabsorption
• Drugs: antiocoagulants, chemotherapy

Question 3

Osteoporosis: pathogenesis

Answer 3

• Age: decreased osteoblast activity with age
• Hormonal: decline in estrogen -> increased cytokine production -> increased RANK-RANKL activity -> suppression of OPG -> increased osteoclast activity
• Physical activity: induces bone remodelling
• Genetic: vitamin D polymorphisms
• Glucocorticoid therapy: increased resorption and decreased bone synthesis

Question 4

Rickets and osteomalacia: pathogenesis

Answer 4

• Diet lacking calcium and vitamin D
• Limited sunlight exposure

Less common causes:

• Renal disorders caused decreased synthesis of 1,25 (OH)2-D
• Phosphate depletion
• Malabsorption disorders

Question 5

Clinical features of Rickets

Answer 5

• Occurs in children

- Deranged bone growth produces skeletal deformities, such as pigeon-breast

Question 6

Clinical features of Osteomalacia

Answer 6

• In adults
• The formed bone is undermineralized, causing weak bones with increased risk for fractures
• Decreased calcium and phosphate
• Increased serum PTH
• Elevated ALP

Question 7

Etiology/types of osteomyelitis

Answer 7

• Pyogenic osteomyelitis: caused by bacteria, usually S. aureus
• Tuberculosis osteomyelitis: complication of pulmonary TB

Question 8

Stages of Paget disease (3)

Answer 8

1. Osteolytic stage: hyperactive, regional osteclast activity and bone resorption; osteoclasts are abnormally large
2. Mixed osteoclastic-osteoblastic stage: lots of bone formation by osteoblasts; marrow is replaced by CT
3. Osteosclerotic stage: exhaustion of cellular activity by osteoclasts; cortex is softened and prone to deformation and fracture

Question 9

Paget disease: clinical features

Answer 9

• Usually affects the axial skeleton or proximal femur
• Symptoms are usually mild, but may include bone pain, hearing loss and lion-like face
• Isolated increased APP

Question 10

Paget disease: pathogenesis

Answer 10

• Rather unknown, but paramyxovirus infection is suggested

Question 11

Bone-forming tumors

Answer 11

• Osteoma: benign, usually seen on the surface of facial bones
• Osteoid osteoma: arises in the cortex of long bones; osteoblasts surrounded by a rim of reactive bone; < 2 cm large
• Osteoblastoma
• Osteosarcoma

Question 12

Osteoid osteoma vs. osteoblastoma

Answer 12

Osteoid osteoma

• In the cortex of long bones
• < 2 cm
• Pain is resolved with aspirin

Osteoblastoma

• In the vertebral column
• > 2 cm
• Pain is not resolved by aspirin

Question 13

Osteosarcoma: etiology, pathogenesis and morphology

Answer 13

• Proliferation of osteoblasts
• Peak incidence among teenagers
• Risk factors: RB gene mutation, Paget’s disease, radiation
• Usually arises in the metaphysis of long bones
• Pathologic fractures are seen with bone pain and swelling

Question 14

Cartilage-forming tumors and their major features

Answer 14

• Osteochondroma: benign cartilage-covered outgrowths attached by a bony stalk
• Chondroma: benign tumor of hyaline cartilage usually seen in small bones of hand and feet
• Chondrosarcoma: malignant tumor producing cartilage; usually seen in the pelvis or central skeleton; painful, progressively enlarging masses

Question 15

Giant cell tumor of bone: major features

Answer 15

• Contains multinucleated giant cells and stromal cells
• In young adults
• Arises in the epiphysis of long bones, usually around the knee
• “Soap bubble” appearance on x-rays

Question 16

Ewing sarcoma and primitive neuroectodermal tumor: major features

Answer 16

• Basically the same tumor, with the same chromosomal abnormality (t(11;22)); they only differ in their degree of differentiation
• Arise from neuroectoderm
• Found in the medullary cavity of the diaphysis of long bones

Question 17

Sources of metastases to the bone

Answer 17

In adults: prostate, breast, kidney, lung
In children: neuroblastoma, Wilms’ tumor, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma

• Usually involves the axial skeleton

Question 18

Causes of muscular atrophy

Answer 18

• Neuropathic atrophy: loss of innervation
• Atrophy caused by disuse: bed rest, immobilization
• Glucocorticoids: Cushing syndrome
• Endogenous hypercortisolism
• Myopathy atrophy

Question 19

Types of muscular dystrophy

Answer 19

• Duchenne and Becker muscular dystrophy
• Autosomal muscular dystrophies: affect specific muscle groups
• Myotonic dystrophy: the main symptom of autosomal muscular dystrophies; AD inheritance associated with CTH trinucleotide repeats

Question 20

Tenosynovial Giant Cell tumor: types and their differences

Answer 20

TGCT is a collective term for closely-related benign neoplasms of the synovium. The main ones are pigmented villonodular synovitis and giant cell tumor of tendon sheath.

• PVNS: diffusely involves joints; monoarticular arthritis; pain, locking and swelling; aggressive lesions erode into adjacent bone and tissue
• GCT: single tendon sheath nodule; solitary, slowly growing painless mass; usually involves wrist and finger tendon sheaths