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