Flashcards in Exam 2- Bones Deck (51):
Which cells have the RANK receptor?
Osteoclasts and Osteoclast Precursors
What happens when RANKL binds the RANK receptor on Osteoclasts?
Binding stimulates survival and generation of Osteoclasts and increases NFKB (not for keeping bone)
What is Osteoprotegrin?
Osteoprotegrin is produced by Stromal Cells or Osteoblasts and inhibites RANKL-RANK receptor interaction
What is M-CSF?
M-CSF is a cytokine produced by osteoblasts or stromal cells that results in the generation and survival of osteoclasts --> increased bone resorption and increased plasma Ca levels
What is the function of the WNT/Beta-Catenin Pathway?
WNT is produced from stromal cells and binds Osteoblasts (through LRP5 and LRP6) to increase secretion of Osteoprotegrin, blocking RANK-RANKL interaction
**Note that a LOF mutation in LRP5/6 --> Osteoporosis and a GOF mutation in LRP5/6 --> Drastic increase in bone mass
What is the main component of the bone's organic matrix?
Type 1 Collagen
What is Woven Bone?
Random Collagen deposition, pathologic, seen in rapid bone growth (ex-healing a fracture)
What are the subtyes of Lamellar Bone? Describe its characteristics
1. Compact Bone
2. Spongy Bone
-Stronger bone with ordered collagen deposition; replaces woven bone
What will be increased with increased Osteoblast activity?
Osteopontin (osteocalcin) and Alkaline Phosphatase
RANK Ligand is located on which cells?
Osteoblasts and Marrow Stroma Cells
The end of a bone (distal to the growth plate) is the
The area beneath the growth plate is call the
The central region of a long bone is the
What is dystosis?
LOCAL problems in migration of mesenchyme and its condensation
Ex- bradydactyly because of HOXD13 defect
What is dysplasia?
GLOBAL defect in regulation of skeletal organogenesis
What is the defect causing Cleidocranial Dysplasia and describe the symptoms
RUNX2 transcription factor defect
-Short stature, abnormal clavicles, wormian bones, too many teeth
What is the cause of Achondroplasia?
FGFR3 mutation --> GOF that inhibits cartilage growth because of decreased chondrocyte proliferation in growth plates
Continuation of appositional and intramembranous bone formation in Achondroplasia results in what?
Thick cortical bone
What are the physical characteristics of Achondroplasia?
Short proximal limbs, normal trunk length, big forehead and head, depressed root of nose
Normal life span, intelligence and reproductive status
What is the cause of Thanatophoric Dwarfism and describe the symptoms
FGFR3 GOF mutation (same as Achondroplasia)
-See short, bowed limbs, frontal bossing with macrocephaly, bell shaped chest (so respiratory failure) and CLOVERLEAF Skull
What is Osteoporosis Pseudoglioma Syndrome?
Disease caused by LOF mutation of LRP5 that causes skeletal fragility and loss of vision
What is the cause of Osteopetrosis (Marble Bone Disease)?
Disease of decreased osteoclast bone resorption caused by a defect in RANKL, LRP5 GOF mutation, or Carbonic Anhydrase II (CAII) deficiency (so cannot acidify pit)
AD- benign, AR- malignant
What are the clinical findings of Osteopetrosis?
1. Extramedullary hematopoiesis --> hepatosplenomegaly
2. Bulbous long bones (erlenmeyer flask deformity)
3. Narrow neural foramina (mild cranial nerve defects)
4. Brittle Bones, multiple fractures
5. Mild anemia
**TREAT- with Bone Marrow Transplant
What is the cause of Osteogenisis Imperfecta?
Mutation in the alpha 1 or alpha 2 chains of TYPE 1 COLLAGEN
What are the clinical characteristics of Osteogenisis Imperfecta?
1. Brittle bones and multiple fractures (may decrease after puberty)
2. Blue Sclerae
3. Hearing Loss
4. Loose joints
What are mucopolysaccharidoses?
Defects in enzymes degrading dermatan sulfate, heparan sulfate and keratan sulfate --> abnormal hyaline cartilage --> malformed bones
What are some potential causes of Osteoporosis?
1. Nutritional (lack of Ca)
2. Menopause (increased RANK/RANKL expression --> increased osteoclast activity)
3. Physical Activity (space flight)
4. Aging (decreased replication of progenitor cells and synthetic activity of osteoblasts)
5. Vitamin D Receptor Polymorphism
6. Drugs, diabetes, malignancy, liver/ GI disease
What is osteoporosis?
A disease of decreased bone mass and increased porosity --> increased risk of fractures
**May be described as osteopenia (decreased bone mass) to the point of risk for fracture
What determines most hereditary osteoporosis?
Vit D receptor, Collagen 1A1 and the Estrogen Receptor
How does decreased estrogen result in Osteoporosis in post-menopausal women?
Decreased Estrogen --> increased inflammatory cytokines that increase RANKL and decrease OPG
**Estrogen replacement is effective treatment, but increases risk of breast cancer
What are common causes of secondary osteoporosis?
1. Hyperparathyroidism (most commonly caused by parathyroid adenoma)
3. Multiple Myeloma
4. Vit. D Defficiency (ricketts and osteomylasia)
What is Dual-energy absorptiometry used for?
Detection of Osteoporosis
Describe the clinical features of Hyperparathyroidism
1. Increased osteoclast fxn --> subperiosteal resorption that thins the cortices
2. Loss of lamina dura around teeth
3. Bone loss on radial aspect of middle phalanges of index and middle finger
4. General Osteopenia
5. Brown Tumor- bone that is replaced by fibrovascular tissue (fractures will result in hemorrhage and you see granulation tissue and hemosiderin)
What is renal osteodystrophy?
-Altered OC/OB activity --> osteomalacia (delayed mineralization), osteosclerosis and osteoporosis
-Decreased activation of Vit D
What are the stages of Paget's Disease?
1. Osteolytic Stage- loss of bone mass due to osteoclasts (see very thick cortex with "V shaped blade of grass" lesion
2. Mixed Stage- Prominent Osteoblasts and Osteoclasts
3. Osteosclerotic Stage- mosaic pattern of lamellar bone- jigsaw puzzle like cement lines
What is the important histological finding of Paget's Disease?
Bone mosaic with disorganized lamellae (look like swirls)
What are the clinical findings of Paget's Disease?
1. Pain from microfractures
2. Increased Alkaline Phosphatase
3. Normal Ca and PO4
4. Bone Overgrowth causing
-Cranial Nerve Palsy
-Heavy skull that is hard to hold up
-Severe secondary osteoarthritis
-Chalk stick-type fracture
Paget's Disease can cause what clinical problems?
1. High-output cardiac failure
2. Tumors (benign and malignant)
What is used to treat Paget's Disease?
Calcitonin and Biphosphonates
Describe the order of healing after a fracture
Soft Tissue Callus (procallus) --> Boney Callus
Procallus- hematoma/fibrin framework that activates osteoprogenitor cells; is not rigid and can be easily disrupted
Boney Callus- made of woven bone +/- cartilage for enchondral ossification
What is avascular necrosis (osteonecrosis) and what are the common causes?
-Infarction of bone and marrow due to vessel injury; the dead bone/fat is replaced by Calcium Soaps
-Causes: *Corticosteroids, infection, dysbarsim, pregnancy, sickle cell disease
What is a medullary infarct?
Subtype of avascular necrosis; can be small or large; large are painful (ex- dysbarism, sickle cell)
What is a Subchondral Infarct?
Subtype of avascular necrosis that results in a WEDGE SHAPED subchondral bone crack; secondary collapse may --> osteoarthritis
How would osteomyelitis appear on an X-Ray?
As a lytic bone lesion with surrounding sclerosis
What are the bacterial causes of osteomyelitis?
1. S aureus
2. E coli, Pseudomonas, Klebsiella (infections of IV drug users)
3. H flue and Group B Strep (infants)
4. Salmonella (Sickle Cell Patients)
Describe the common locations for osteomyelitis for different age groups
1. Neonate- Metaphysis or Epiphysis
2. Children- Metaphysis
Adult- Epiphyses and subchondral bone
What is a Brodie Abscess?
A small intraosseous abscess often in the cortex walled off by reactive bone
What is Sclerosing Osteomyelitis of Garre
Osteomyelitis in the jaw with extensive new bone formation
A draining sinus of pyogenic osteomyelitis can develop into what?
Squamous Cell Carcinoma
What is the clinical characteristics of TB Osteomyelitis?
1. Occurs in immunosuppressed
2. Pott's Disease: Lumbar and Thoracic Spine --> breaks through discs to other vertebrae --> scoliosis and kyphosis