Term
| What is mechanotransduction? |
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Definition
| osteocytes-osteoblasts surrounded by newly deposited organicmatrix- detect mechanical forces and translate them into biologic activity |
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Term
| What are the cytokines and growth factors that regulate human osteoclast differentiation? |
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Definition
macrophage colony-stimulating factor (M-CSF)
IL-1, TNF |
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Term
| How does the osteoclast remove the mineral from bone? |
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Definition
| generating an acidic environment utilizing a proton pump system and digests the organic component by releasing proteases |
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Term
| What genes determine skeletal morphogenesis? |
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Definition
| Homeobox genes, which encode trc factors essential for the normal development of the skeleton |
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Term
| What is enchondral ossification and when does it begin? |
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Definition
8th week of gestation
cartilage is removed by osteoclast-type cells forming the medullary canal. This process progresses along the length of the bone |
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Term
| What is the primary center of ossification? |
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Definition
| periosteum in the mid-shaft that generates osteoblasts that deposit the beginnings of the cortex |
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Term
| Secondary center of ossification |
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Definition
| similar to primary but occurs in the epiphysis, resulting in the removal of cartilage and deposition of bone in a centrifugal fashion |
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Term
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Definition
the plate of cartilage anlage that becomes entrapped between the expanding primary and secondary centers of ossification
aka physis |
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Term
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Definition
| developmental anomalies resulting from localized problems in the migration of the mesenchymal cells and the formation of the condensations |
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Term
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Definition
Mutations in the regulators of skeletal organogenesis, such as signaling molecules and matrix components
-affect cartilage and bone tissues globally |
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Term
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Definition
MOST COMMON disease of the growth plate and is a major cause of dwarfism
-caused by mutation in FGF receptor 3 that causes constitutive activation of FGFR3 and thereby suppresses growth |
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Term
| What is the most common LETHAL FORM of dwarfism? |
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Definition
Thanatophoric Dwarfism
-gain of function mutation of FGFR3 diff from mutation in achondroplasia
-frequently die at birth or shortly after |
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Term
| Inactivating mutation in LRP5 causes what? |
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Definition
OSTEOPOROSIS PSUEDOGLIOMA SYNDROME
skeleton is severely osteoporotic resulting in fractures due to insufficient bone formation.
LRP5 is necessary for OBs to secrete OPG which blocks RANKL from RANK thus regulating OC proliferation |
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Term
| Osteogenesis Imperfecta (brittle bone disease) OI |
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Definition
Caused by deficiencies in synthesis of TYPE I COLLAGEN
MOST COMMON inherited disorder of connective tissue
Blue sclerae, hearing loss, dental imperfections
*basic abnormality in all forms of OI is TOO LITTLE BONE |
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Term
| What type of OI is lethal? |
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Definition
TYPE II
perinatal lethal- death in utero or within days of birth
autosomal recessive inheritance |
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Term
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Definition
TYPE II COLLAGEN
-short trunk, severely shortened extremities, relatively enlarged cranium, flattened face |
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Term
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Definition
TYPE II COLLAGEN
-same as achondrogenesis II |
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Term
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Definition
TYPE II COLLAGEN
-myopia, retinal detachment, hearing loss, flattened face, premature osteoarthritis |
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Term
| Multiple epiphyseal dysplasia |
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Definition
TYPE 9 COLLAGEN
-short or normal stature, small epiphyses, early-onset osteoarthritis |
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Term
| Schmid metaphyseal chondrodysplasia |
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Definition
TYPE 10 COLLAGEN
-mildly short stature, bowing of lower extremities, coxa vara, metaphyseal flaring |
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Term
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Definition
group of lysosomal storage diseases that are caused by deficiencies in the enzymes that degrade dermatan sulfate, heparan sulfate, and keratan sulfate
-many of the skeletal manifestations result from abnormalities of hyaline catilage |
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Term
Osteopetrosis
Marble bone disease
Albers-Schonberg disease |
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Definition
Impaired formation or function of OSTEOCLASTS
-bones are abnormally brittle and fracture easily
-MOST COMMON VARIANTS: autosomal recessive severe type and the autosomal dominant mild type |
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Term
| Morphology of Osteopetrosis |
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Definition
ERLENMEYER FLASK DEFORMITY
long bones are bulbous and misshapen
deposited bone is not remodeled and tends to be woven in architecture |
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Term
| Three phases of Paget's Disease |
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Definition
1. osteolytic phase
2. mixed phase: osteoclastic-osteoblastic stage, ends with a predominance of osteoblastic activity
3. osteosclerotic phase
NET EFFECT: gain of bone mass but new bone is disordered and architecturally unsound |
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Term
| Hallmark mophology of Paget's |
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Definition
MOSAIC PATTERN OF LAMELLAR BONE
In the end bone becomes a "caricarture" of itself
-larger than normal and composed of coarsely thickened trabeculae and cortices that are soft and porous and lack structural stability |
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Term
| Clinical features of Paget's |
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Definition
VARIABLE
1. PAIN localized to affected bone caused by microfractures that compress spinal and cranial nerve roots
2. leontiasis ossea - enlargement of the craniofacial skeleton, so heavy can't hold head up
3. chalkstick-type fractures: usually occur in the long bones of the LE
4. weight bearing causes anterior bowing of the femurs and tibiae and distorts femoral heads |
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Term
| What tumors are associated with Paget's? |
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Definition
| Giant-cell tumor, giant-cell reparative granuloma, extra-osseous masses of hematopoiesis and SARCOMA |
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Term
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Definition
Associated with hyperparathyroidism
-Bone loss predisposes to microfractures and secondary hemorrhages that elicit an influx of macrophages and an ingrowth of reparative fibrous tissues creating a MASS of reactive tissue
-brown color is the result of the vascularity, hemorrhage and hemosiderin deposition |
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Term
| von Recklinghausen disease of bone |
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Definition
| combined picture of increased bone cell activity, peritrabecular fibrosis, and cystic brown tumors is the hallmark of severe hyperparathyroidism and is also known as generalized osteitis fibrosa cystica |
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Term
| 5 skeletal changes found in renal osteodystrophy |
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Definition
1. increased OC bone resorption - mimic osteitis fibrosa cystica
2. delayed matrix mineralization - osteomalacia
3. osteosclerosis
4. growth retardation
5. osteoporosis |
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Term
| Pathogenesis of renal osteodystrophy |
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Definition
1. Phosphate retention
2. secondary hyperparathyroidism - phosphate induces PTH
3. hypocalcemia- develops as levels of vitamin D fall because decreased conversion to active 1,25-(OH)2D3 in kidneys (renal hydroxylase is inhibited)
4. metabolic acidosis - stimulates bone resorption
5. aluminum deposition- interferes with deposition of calcium hydroxyapatite resulting in osteomalacia
6. amyloid deposition |
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