Flashcards in Congenital and Acquired Disease of Bone Development Deck (55):
____ is bone that has not been mineralized
What are osteoprogenitor cells?
Pluripotential mesenchymal stem cells. Under CBFA-1 stimulation they can become osteoblasts. They can also become macrophages.
____ sense mechanical stress and regulate serum calcium and phosphorous
_____ mediates osteoclasts and have PTH receptors
Composition of osteoid
type 1 collagen, 90% of organic part
Role of osteoblasts
synthesize osteoid, initiate mineralization, become surrounded by matrix and become osteocytes, mediate osteoclast activity, have PTH receptors
_____ are incased in bone and communicate through canaliculi
Osteoclasts require what cytokines for differentiation?
IL1,3,6,11, GM-CSF, M-CSF
Where do osteoclasts reside?
resorption pits, howship lacunae
____ are multinucleated cells responsible for resorption and remodeling.
What pararcine signals allow precursor cells to produce functional osteoclasts?
Osteoblast/ stromal cell membrane-associated RANK ligand (RANKL) binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction in the background of macrophage colony-stimulating factor (M-CSF) causes the precursor cells to produce functional osteoclasts
what does osteoprotegerin do?
Stromal cells also secrete osteoprotegerin (OPG) which acts as a decoy receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently OPG prevents bone resorption by inhibiting osteoclast differentiation
_____ is the cartilage between ossification centers.
Growth plate is in which part of the bone?
Why are children more prone to osteomyelitis?
richer blood supply
Describe the blood supply in growing bone vs mature bone
Growing: blood is supplied to growth plate in epiphysis.In mature bone, metaphyseal vessels penetrate the cartilage plate
OI is a family of diseases having in common mutations in _____.
type 1 collagen genes
What are the classic subtypes of OI
1- too litte pro-a1 made. 2-Pro-a1 is too short (lethal in urtero. 3) triple helix doesnt form well. 4) pro-a2 is too short
OI mode of inheritance
most are AD; 2 is either recessive or new AD
What are the 4 major clinical criteria of OI?
osteoporosis, blue sclerae, dintinenesis imperfecta, premature otosclerosis
Is OI the only thing you see blue sclera with?
No- things like ehlers danlos and rarely anemia, RA, and myasthenia gravis
What are the 2 clinical types of OI?
congenital and tarda
_____ is the most common cause of inherited dwarfism and is AD.
What causes achondroplasia?
reduction in chondrocytes at growth plate,
What is the specific mutation associated with achondroplasia?
receptor for fibroblast growth factor 3
What do limbs look like with achondroplasia?
short extremities with abnormally wide ends. normal trunk, large head with large forehead, deep set nose, prominent supraorbital ridges
What is a danger to life with achondroplasia?
deformity at the foramen magnum where minor trauma can cause compression of brain stem.
_____ is a known risk factor for new mutations with achondroplasia.
advanced paternal age
What do xrays of osteopetrosis show?
long bones without medullary cavities and misshapen, bulbous ends. Diffusely sclerotic.
What causes osteopetrosis?
a failure of osteoclasts to resorb bone tissue, resulting in bone marrow
becoming occluded by weak, woven bone. The bone is brittle (breakable) and crowds marrow; patients are typically neutropenic and anemic.
Bones in osteopetrosis lack a _____.
Describe the ARO variant of osteopetrosis and how it is treated.
The most severe form of human osteopetrosis is the
malignant, infantile, autosomal recessive variant (ARO). ARO occurs because of specific mutations in genes responsible for osteoclast function. Despite a decrease in resorption, osteoclast numbers are normal or increased. These ‘‘osteoclast-rich’’ cases suggest that the osteoclast defect does not affect osteoclast formation but rather lies in their mature functional capacity. Providing osteoclast precursors via bone marrow
transplantation successfully treats these patients.
Describe osteopetrosis caused by LOF RANK mutation
very low number of osteoclast in bone
What is the role of RANK in osteoclasts?
Osteoclasts and their precursors bear a membrane receptor called RANK which activates the NF-kB signaling pathway and is instrumental in osteoclast differentiation. Activation occurs when the ligand of RANK is present. RANKL is synthesized by osteoblasts and mesenchymal stem cells.
______ is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk
What are some major risk factors for osteoporosis?
age over 70, menopause before 45, hypogonadism, fragility fracture, hip fracture in parents, GC, malabsorption, high bone turnover, anorexia, BMI<18, immobilization, chronic renal failure, transplantation
What are some moderate risk factors for osteoporosis?
estrogen deficiency, low calcium intake, primary hyperparathyroidism, RA, hyperthyroidism, diabetes mellitus, smoking, alcohol excess, anticonvulsants, bechterew disease
What is involved in the pathogenesis of osteoporosis?
Increased bone loss due to formation that does not match resorption or increased number of remodeling units. With menopause, there is increased IL1,6,and TNF, decreased estrogen, and increased RANK and osteoclast activity. With aging, there is decreased replicative activity of progenior cells, physical activity, activity of osteoblasts.
What might you see with osteoporosis on X ray and histology?
compression fractures, thin trabeculae with microfractures
____ is associated with high early mortality with osteoporosis.
What is Paget disease?
Unbalanced and excessive osteoclast and osteoblast function; increased bone turnover
What are different patterns of pagets disease?
Osteolytic, mixed osteolytic-osteoblastic, osteoblastic and burnt-out stages
What does Paget's do to the bone?
Mosaic pattern of lamellar bone; skull and long bones; deforms bones
Etiology of Paget's
Painful, mid-adulthood; Northern Europeans
People with Pagets are predisposed to
osteogenic sarcoma, chondrosarcoma, and malignant fibrous histiocytoma
Key clinical points of Pagets
thick skull, deafness, kyphosis, pain, bowed legs
A young patients that has osteosarcoma can present in older age with ____
______ is failure of the bone to mineralize properly in adults.
What should you consider first as the cause of osteomalacia?
Vitamin D or calcium
What does osteomalacia/Rickets look like histologically?
Surfaces of bony trabeculae are covered by thicker than normal layer of osteoid
Look at renal osteodystrophy slide?
what is this?!
What causes primary hyperparathyroidism? Secondary?
Primary: adenoma. Secondary: prolonged hypocalcemia
What does hyperparathyroidism result in?
stimulation of osteoclast and bone resorption
What are 3 different things that can result from hyperparathyroidism?
– Osteoclasts bore into center of trabeculae
– X-ray: railroad tracks along length of bone and decrease in bone density (osteopenia)
Brown tumors: microfractures and hemorrhage; hemosiderin deposition; fibrosis
Osteitis fibrosa cystica: Increased bone activity + peritrabecular fibrosis + cystic brown tumors