Musculoskeletal Pathology Flashcards
What is Achondroplasia?
$ What causes it?
Impaired cartilage proliferation in the growth plate;
$ Due to an activating mutation in fibroblast growth factor receptor 3 (FGFR3); autosomal dominant
- Overexpression of FGFR3 inhibits growth.
- Most mutations are sporadic and related to increased paternal age.
$ What are the clinical features of Achondroplasia?
What is the difference between endochondral and intramembranous bone formation?
How does this disease affect mental function, life span, and infertility?
Short extremities with normal-sized head and chest - due to poor endochondral bone formation; intramembranous bone formation is not affected.
Impaired proliferation of cartilage at the growth plate
Gene mutations increase with paternal age
Endochondral bone formation is characterized by formation of a cartilage matrix, which is then replaced by bone; it is the mechanism by which long bones grow.
Intramembranous bone formation is characterized by formation of bone_ without a preexisting cartilage_ matrix; it is the mechanism by which flat bones (e.g., skull and rib cage) develop.
Mental function, life span, and fertility are not affected.
What is Osteogenesis imperfecta?
Cause?
Congenital defect of bone resorption resulting in structurally weak bone
Most commonly due to an autosomal dominant defect in collagen type I synthesis
$ Clinical features of Osteogenesis imperfecta?
Treatment?
1.. Multiple fractures of bone (can mimic child abuse, but bruising is absent)
$ 2. Blue sclera- Thinning of scleral collagen reveals underlying choroidal veins.
3. Hearing loss- Bones of them iddle ear easily fracture.
Bisphosphonates to increase bone mineralization
What is Osteopetrosis?
The cause is due to poor functioning of this cell?
$ Explain the mechanism of how the normal process involving bone goes wrong.
Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
Due to **poor osteoclast function. **deficiency of osteoclasts; “too much bone”
Multiple genetic variants exist; carbonic anhydrase II mutation leads to **loss of the acidic microenvironment required for bone resorption. **Overgrowth and sclerosis of cortical bone (“too much bone”
$ What are the clinical findings in osteopetrosis (“marble bone disease”)
- Bone fractures
- Anemia, thrombocytopenia, and leukopenia with extramedullary hematopoiesis- due to bony replacement of the marrow (myelophthisic process,
- Vision and hearing impairment-due to impingement on cranial nerves
- Hydrocephalus-due to narrowing of the foramen magnum
- $ Renal tubular acidosis- seen with carbonic anhydrase II mutation
i. Lack of carbonic anhydrase results in decreased tubular reabsorption of HC03 -,leading to metabolic acidosis.
$ What is the treatment for Osteopetrosis? Why does this treatment work?
Treatment is bone marrow transplant; osteoclasts are derived from monocytes
- Pathogenesis in this disease is a Deficiency of osteoclasts*
- Normal balance of osteoblasts making bone and osteoclasts breaking down bone is disrupted favoring increased bone formation.*
- Osteopetrosis: deficiency of osteoclasts; “too much bone”*
What is osteomalacia?
What causes this condition?
Defective mineralization of osteoid
Osteoblasts normally produce osteoid, which is then mineralized with calcium and phosphate to form bone.
Due to low levels of vitamin D, which results in low serum calcium and phosphate
Rickets is due to low vitamin D in children, resulting in abnormal bone mineralization.
Where is Vitamin D normally derived from?
How is it activated?
Vitamin Dis normally derived from the skin upon exposure to sunlight (85%) and from the diet (15%).
Activation requires 25-hydroxylation by the liver followed by 1-alpha-hydroxylation by the proximal tubule cells of the kidney.
Name 3 ways Active vitamin D raises serum calcium and phosphate.
Active vitamin D raises serum calcium and phosphate by acting on
i. Intestine- increases absorption of calcium and phosphate
ii. Kidney-increases reabsorption of calcium and phosphate
iii. Bone-increases resorption of calcium and phosphaLe
What conditions cause Vitamin D deficiency?
Vitamin D deficiency is seen with decreased sun exposure (e.g., northern latitudes), poor diet, malabsorption, liver failure, and renal failure.
$ What age does Rickets usually present? How does this condition commonly present?
Most commonly arises in children < 1 year of age; presents with:
i. Pigeon-breast deformity-inward bending of the ribs with anterior
protrusion of the sternum
ii. Frontal bossing (enlarged forehead)-due to osteoid deposition on the skull
iii.$ Rachitic rosary - due to osteoid deposition at the costochondral junction
iv. Bowing of the legs may be seen in ambulating children.
$ Lab findings in Osteomalacia in adults?
Laboratory findings include
- ↓ serum calcium
- ↓ serum phosphate
- ↑ PTH
- ↑ alkaline phosphatase (any time osteoblasts are activated)
Inadequate mineralization results in weak bone with an increased risk for fracture.
Osteoporosis
- Reduction in trabecular bone mass
- Results in porous bone with an increased risk for fracture
What is risk of osteoporosis based on?
Risk of osteoporosis is based on peak bone mass (attained in early adulthood) and rate of bone loss that follows thereafter.
- Peak bone mass is achieved by 30 years of age and is based on (1) genetics (e.g., vitamin D receptor variants), (2) diet, and (3) exercise.
- Thereafter, slightly less than 1% of bone mass is lost each year; bone mass is lost more quickly with lack of weight-bearing exercise (e.g., space travel), poor diet,
or decreased estrogen (e.g., menopause).
Most common forms of osteoporsis?
Most common forms of osteoporosis are senile and postmenopausal.
Clincal findings in osteoporosis?
How is bone density measured?
- Bone pain and fractures in weight-bearing areas such as the vertebrae (leads to loss of height and kyphosis), hip, and distal radius
- Bone density is measured using a DEXA scan.
Most common metabolic abnormality of bone
Osteoporosis
Classification of Osteoporosis?
- (1) Primary**
(a) Most common type (80% women, 60% men)
(b) Idiopathic type in children and young adults
(c) Postmenopausal type (most common)
(d) Senile type in men and women
- (1) Primary**
** (2) Secondary**
** Secondary causes: ↑ cortisol, heparin, hypogonadism, malnutrition, space travel**
(a) Underlying disease (e.g., hypercortisolism)
(b) Drugs (e.g., heparin)
(c) Hypogonadism (e.g., hypopituitarism)
(d) Malnutrition (e.g., anorexia nervosa)
(e) Space travel
Lack of gravity reduces bone stress.
$ What do serum labs show in osteoporosis? What other disease do labs allow you, the physician, to differentiate between?
Serum calcium, phosphate, PTH, and alkaline phosphatase are normal; labs help to exclude osteomalacia (which has a similar clinical presentation).
Pathogenesis of Postmenopausal osetoporosis?
Pathogenesis of Senile osteoporosis?
Due to estrogen deficiency
(1) Increased resorption of bone by osteoclasts
* *↓ Estrogen: ↑ osteoclastic activity, ↓ osteoblastic activity**
(2) Decreased formation of bone by osteoblasts
Senile osteoporosis
** Decreased ability of osteoblasts to divide and produce osteoid**
Treatment for osteoporosis?
- Exercise. vitamin D. and calcium-limit bone loss
- Bisphosphonates-induce apoptosis of osteoclasts
- Estrogen replacement therapy is debated (currently not recommended).
- Glucocorticoids are contraindicated (worsen osteoporosis).
What is Paget’s disease of the bone?
Describe the pathogenesis?
Osteitis deformans
Imbalance between osteoclast and osteoblast function
Usually seen in late adulthood (average age> 60 years)
Etiology is unknown; possibly viral
Three distinct stages are
(1) osteoclastic,
(2) mixed osteoblastic-osteoclastic, and
(3) osteoblastic.
I. End result is thick, sclerotic bone that fractures easily.
- Paget’s disease: osteoclastic phase followed by an osteoblastic phase*
- Early phase of osteoclastic resorption of bone
Causes shaggy-appearing lytic lesions
Late phase of increased osteoblastic bone formation
(1) Markedly increased serum alkaline phosphatase* - Paget’s disease: ↑ alkaline phosphatase in osteoblastic phase*
- (2) Production of thick, weak bone (mosaic bone*
$ What are the clinical findings in Paget’s disease?
- *1. Bone pain - due to microfractures of weak, thick, vascular bone (most common complaint)**
2. Increasing hat size - Skull is commonly affected.
3. Hearing loss - impingement on cranial nerve
4. Lion-like facies - involvement of craniofacial bones - *5. $Isolated elevated alkaline phosphatase- most common cause of isolated elevated alkaline phosphatase in patients> 40 years old**
Treatment for Paget’s disease
- Calcitonin- inhibits osteoclast function
- Bisphosphonates-induces apoptosis of osteoclasts
$ Complications of Paget’s disease?
High-output cardiac failure- due to formation of AV shunts in bone
Osteosarcoma
What is osteomyelitis? Whom does it normally occur in?
Infection of marrow and bone
1. Usually occurs in children
$ What part of the bone is osteomyelitis seen in children vs. adults?
Most commonly bacterial; arises via hematogenous spread
- *1. Transient bacteremia (children) seeds metaphysis.
2. Open-wound bacteremia (adults) seeds epiphysis.**
Causes of Osteomyelitis?
- Staphylococcus aureus-most common cause (90% of cases)
- N gonorrhoeae-sexually active young adults
- **Salmonella paratyhpi **-sickle cell disease
- Pseudomonas- Most often due to puncture of foot through rubber footwear, diabetics or IV drug abusers
- Pasteurella-associated with cat or dog bite/scratches
- Mycobacterium tuberculosis-usually involves vertebrae (Port disease)
Neutrophils enzymatically destroy bone
Findings in osteomyelitis?
How is diagnosis made?
Bone pain with systemic signs of infection (e.g., fever and leukocytosis)
** Lytic focus** (abscess) surrounded by sclerosis of bone on x-ray; lytic focus is called sequestrum, and sclerosis is called involucrum.
Diagnosis is made by blood culture.
Avascular (Aseptic) necrosis
Cause?
Complications?
A. Ischemic necrosis of bone and bone marrow
B. Causes include trauma or fracture (most common), steroids, siclde cell anemia, and caisson disease.
C. Osteoarthritis and fracture are major complications.
3 major causes of aseptic necrosis of bone?
Causes
(1) Corticosteroids (35%)
(2) Alcohol (22%)
(3) Other causes (43%)
(a) Idiopathic
(b) Fractures
Aseptic necrosis: femoral head most common site
What is Osteochondrosis?
Aseptic necrosis of ossification centers in children
Legg-Calvé-Perthes disease
** Legg-Calvé-Perthes disease: aseptic necrosis of femoral head ossification center**
(1) Aseptic necrosis involving the femoral head ossification center
(2) Occurs most often in boys 3 to 10 years of age
(3) Presents with pain in the knee or a limp
(4) Secondary osteoarthritis is common.
Fibrous dysplasia
Fibrous dysplasia is a lesion in which portions of the bone are replaced by fibrous connective tissue and poorly formed trabecular bone.
Fibrous dysplasia may occur in single or multiple bones (monostotic and polyostotic fibrous dysplasia, respectively). The polyostotic form of fibrous dysplasia is known as McCune-Albright syndrome (or Albright syndrome, MIM #174800) and is associated with endocrine abnormalities and café-au-lait spots
Defect in osteoblastic differentiation and maturation, Skeletal developmental anomaly
Defect in bone-forming mesenchyme with replacement of medullary bone by fibrous tissue
Defect in osteoblastic differentiation and maturation
Fibrous dysplasia: medullary bone replaced by fibrous tissue with cyst formation
Cysts may develop in the fibrous tissue matrix that manifests as a defect in osteoblastic differentiation and maturation.
Occurs between 10 and 30 years of age
Clinical findings
Pain overlying the bone
Swelling of bone
Complications: pathologic fracture, osteogenic sarcoma, fibrosarcoma
Most common site of fibrous dysplasia?
ribs most common site
Albright’s syndrome.
Polyostotic bone involvement is associated with Albright’s syndrome.
** Albright’s syndrome: polyostotic bone involvement; café au lait spots; precocious puberty**
Café au lait spots on skin Precocious sexual development
Clinical findings
Pain overlying the bone Swelling of bone
What would imaging of an osteoid osteoma show?
Imaging reveals a bony mass (< 2 cm) with a radiolucent core (osteoid).
A) Full (look at the femur) and B) coned views of the midshaft of the femur demonstrate a dense sclerotic zone of cortical thickening laterally, which contains a small oval lucent nidus (arrow).
A 15 year old boy presents to your clinic with a limp. He complains of pain in his hip. No relief is obtained with NSAIDs. Diagnosis?
$ How do you distinguish between osteoid osteoma and osteoblastoma?
Osteoblastoma is similar to osteoid osteoma but is larger (> 2 cm), arises in vertebrae, and presents as bone pain that does not respond to aspirin.
rare benign bone-forming tumor of unknown etiology.
The radiographic findings of osteoblastoma are variable. Above, an expansile, eccentric mass in the proximal humerus causes thinning of the cortex (arrows)
Draw the major components of a long bone.
Imaging of Osteosarcoma?
$ Biopsy?
Imaging reveals a destructive mass with a ‘sunburst’ appearance and lifting of the periosteum
Biopsy reveals $ pleomorphic cells that produce osteoid
malignant osteoid (arrows) with pleomorphic malignant osteoblasts.
Diagnosis?
OSTEOSARCOMA
Imaging reveals a destructive mass with a ‘sunburst’ appearance and lifting of the periosteum (Codman triangle
$ Diagnosis?
$ ‘Soap-bubble’ appearance on x-ray
Locally aggressive tumor; may recur
Giant cell tumor
$Interpret these findings under polarized light.
Pseudogout resembles gout clinically, but is due to deposition of calcium pyrophosphate dihydrate (CPPD);
synovial fluid shows rhomboid-shaped crystals
with weakly positive birefringence under polarized light.
