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What are paraneoplastic syndromes that result in excess PTH-like substance?
Squamous Cell Carcinoma, Renal Cell Carcinoma
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What's the primary cause of hyperparathyroidism?
Parathyroid Adenoma
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What's the most common cause of secondary hyperparathyrodism?
Renal Failure
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What's a common clinical presentation of vitamin D deficiency?
Bone issues
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What's a common presentation of vitamin C deficiency?
Bone & Bleeding issues
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What's the connection between primary hyperparathyrodism and pancreatitis?
Activation of trypsin --> pancreatitis
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At what levels do you see symptoms of hypercalcemia? Organ calcification?
Coma/cardiac arrest?
- Symptoms > 11.5
- Organs > 13
- Coma/arrest >15
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What are functions facilitated by calcium levels?
Cell signaling, neuromuscular function, bone metabolism
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Through what mechanisms does PTH regulate calcium?
Renal tubular reabsorption, osteoclast stimulation, renal 1 hydroxylase activity
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What's the mechanism of calcitonin's suppression of Ca levels?
Inhibits osteoclasts
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What's the histological findings in bone lesions?
- Increased osteoclastic activity
- fibrous tissue replacement of bone
- thinned trabeculae
- cystic spaces
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What are brown tumors characteristic of?
- Hyperparathyroidism
- Osteoclasts, giant cells, hemorrhagic debris
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Where are metastatic calcifications found in secondary hyperparathyroidism?
Vessels, lung, heart, stomach
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What does the term Renal Osteodystrophy describe?
Bone changes secondary to chronic renal failure (atrophied bone)
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What is characteristic of osteomalacia?
Decreased bone matrix mineralization with normal matrix (vs. osteoporosis)
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What's the difference between parathyroid adenoma vs. carcinoma?
Metastases
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What are lab findings in osteoporosis?
Normal calcium, phosphate, PTH
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What's the mechanism of postmenopausal osteoperosis?
- Increased cytokine --> activation of osteoclasts
- TNF -> RANK(L)
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What's the mechanism of senile osteoporosis?
Decreased osteoblast function
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Where are the most common fractures found in osteoporosis?
- Vertebrae, weight bearing bones
- Usually asymptomatic
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What's the best way to diagnose osteoporosis?
Bone mineral densitomerty
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What's the effect of estrogen on bone?
Reduction in osteoclastogenensis;
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What are risk factors for bone fractures?
Fracture history, glucocorticoid use, cigarette smoking, alcoholism, family history of fracture, low bodyweight
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What is Osteits Deformans?
Paget Disease
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What is the gold standard for assessing bone mineral density?
- Dual-Energy x-ray absorptiometry (DXA) of spine & hip
- Osteopenia: (-1.0) - (-2.5) SD
- Osteoperosis: < -2.5 SD
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In what disease is morning joint stiffness MOST common?
Rheumatoid Arthritis
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What clinical findings are present in Rheumatoid Arthritis?
Morning stiffness, bilateral pain, MCP joint involvement, swan neck deformities
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What is a swan-neck deformity and when is it found?
Hyperextension of PIP; RA
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When are osteophytes found?
Bony outgrowths found in osteoarthritis
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What are risk factors for osteoarthritis?
Obesity, diabetes, ochronosis, hemochromatosis, trauma/overuse, bone/joint deformities
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Where are common joints of involvement for OA?
- Large: intervertebral, hips, knees
- DIP
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What's the most commn joint disorder in the US?
Osteoarthritis
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What are heberden nodules and when are they found?
Osteophytes at DIPs in OA
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What are bouchard nodules and when are they found?
Osteophytes at PIP joints found in OA
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What histological findings are characteristic of RA in the joints?
Synovial hyperplasia, lymphocytosis, involvment of smaller joints
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What are complications of HFE gene mutations?
- Hemochromatosis:
- Iron absorption, cirrhosis, cardiomyopathy, diabetes, OA
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What's the common demographic of osteosarcoma?
- 10-20 y/o
- Elderly with prior Paget's Disease/radiation exposure
- Males
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Where are common sites of involvement for Osteosarcoma?
- Young - femur or tibial metaphysis
- Old - axial or craniofacial
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What's the common gross presentation of osteosarcoma?
- Blastic/lytic masses with infiltrative margins
- Elevation of periosteum = Codman Triangle
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Where are most common metastases locations of osteosarcoma?
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What's the definition of and osteosarcoma?
Any malignant cell that produces osteoid (regardless of what else may be produced)
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What's the most common primary bone tumor?
Osteosarcoma
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What are common mutations found in osteosarcomas?
- Sporadic: RB & p53
- Familial: Rb, associated hereditary retinoblastomas
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What are common clinical symptoms of Paget Disease?
- asymptomatic
- bone pain, fractures, anterior tibial bowing, warmth & tenderness, cardiac failure
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What's a common lab presentation for paget disesase?
- Increased alkaline phosphatase (5x)
- Increased urinary hydrokyproline
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What's the most common location for Paget's disease?
- Axial skeleton (80%) - also skull, tibia, pelvis
- Polyostotic (85%)
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What's the histological pattern of Paget's disease?
Mosaic pattern from disorganized degeneration/regeneration
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What are the stages of Paget's disease?
- 1. osteolytic
- 2. mixed
- 3. osteosclerotic
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What are complications of paget's disease?
- Skeletal deformities
- Nerve compression (deafness)
- Increased vascularity (AV shunting -> high output cardiac failure)
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What neoplasmic sequelae follow Paget's diesease?
Osteosarcoma, MFH, chondrosarcoma in 10%
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What are most commonly involved sites of chondrosarcoma?
Axial skeleton (ribs, shoulder, pelvis), proximal femur & pelvis
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What are the most common etiologies of chondrosarcomas?
- Primary (85%) from previously normal bones
- Secondary (15%) from benign precursors
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What's a histological characteristic of chondrosarcoma?
2+ cells per lacuna
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What's the metastasis profile of chondrosarcoma?
- Typically slow growing (slow to metastsize)
- De-Differentiated chondrosarcomas: rapid metastases in lung, brain, bone
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What's the metastasis profile of osteosarcomas?
20% have pulmonary metastases at diagnosis
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