Bone - Important Concepts Flashcards
Endochondrial ossification
Bones of axial and appendicular skeleton and base of skull.
Cartilage (Chondrocytes) –> Woven bone (osteoclasts and osteoblasts) –> Lamellar bone
In adults, woven bone occurs after fractures and in Paget disease.
Membranous ossification
Bones of calvarious and facial bones Woven bone (osteoclasts and osteoblasts) --> lamellar bone (unlike endochondrial ossification which has a cartilage phase first)
What do osteoblasts differentiate from?
What do osteoclasts differentiate from?
Mesenchymal stem cells in the periosteum ( membrane that covers the outer surface of all bones,[1] except at the joints of long bones)
Monocytes / macrophages
What are osteoclasts?
Multinucleated cells - they dissolve bone by secreting acids and collagenases.
Low effects of PTH versus high effects?
Low levels - anabolic effects
Chronic high PTH - catabolic effects - osteitis fibrosis cystica
Estrogen effects on bone?
Inhibits apoptosis in osteoblasts
Induces apoptosis in osteoclasts
What happens with estrogen deficiency?
Excess remodeling cycles and bone resorption –> osteoporosis
Failure of longitudinal bone growth and endochondrial ossification
Achondroplasia, caused by FGFR-3 mutation on chromosome 4, which constitutively activates it, autosomal dominant. Membranous ossification is not affected so large head relative to limbs.
Achondroplasia
Achondroplasia, caused by FGFR-3 mutation on chromosome 4, which constitutively activates it, autosomal dominant. Membranous ossification is not affected so large head relative to limbs.
Associated with advanced paternal age. >85% of mutations occur sporadically.
For osteoporosis what will lab values look like?
Normal
How is osteoporosis diagnosed?
DEXA scan with T score < -2.5
Type I osteoporosis
Postmenopausal - increased bone resorption due to decreased estrogen levels.
Associated with femoral neck fracture, distal radius / Colles fractures
Type II osteoporosis
Senile osteoporosis - affects men and women > 70 years old.
Treatment of osteoporosis
Bisphosphonates, PTH, SERMs
Rarely calcitonin, denosumab (monoclonal antibody against RANKL)
Failure of normal bone resorption due to defective osteoclasts. Thickened, dense bones prone to fracture. Pancytopenia. Extramedullary hematopoiesis. Cranial nerve impingement.
Osteopetrosis (marble bone disease)
Osteopetrosis (marble bone disease)
Failure of normal bone resorption due to defective osteoclasts. Thickened, dense bones prone to fracture. Pancytopenia. Extramedullary hematopoiesis. Cranial nerve impingement.
Mutations such as carbonic anhydrase II impair ability of osteoclast to generate acidic environment necessary for bone resorption.
Cure with bone marrow transplant - osteoclasts are derived from monocytes.
X ray showing bone-in-bone appearance
Osteopetrosis
How can you cure osteopetrosis?
Bone marrow transplant - osteoclasts are derived from monocytes