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What are two hereditary diseases of the bone?
- Osteogenesis imperfecta (OI): aka brittile bone disease
- Osteopetrosis: (marble bone disease)
- There are a number of hereditary disorders of the bone that interfer with the bone growth by affecting maintenance of a normal osteoid matrix.
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What is Osteogenesis Imperfecta?
Genetic?
Most severe problem with OI?
Clinical manifestations?
Prognosis?
- Group of hereditary bone disorders with abnormal synthesis/development of type I collagen. This causes SKELETAL FRAGILITY and "brittle bone disease"
- Most are autosomal dominant (4 variants)
- In most severe forms, death results from passage through birth canal.
- Blue sclera and opalescent teeth (dentinogensis imperfecta) are components.
- Prognosis depends on type of OI and expression of the gene.
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Osteopetrosis: What is it?
affect on bone structure?
Treatment?
- aka "marble bone disease"
- Group of rare hereditary bone disorders with defective bone remodeling (osteoclast dysfunction)
- Affected bone is dense, but structurally unsound and weak.
- Prone to fracture, cranial nerve compression and infections.
- Bone marrow transplantation may re-populate functional osteoclasts (derived from monocyte precursors)
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Osteopetrosis:
Density of bone causes what?
Predisposed to what?
Compression of marrow area causes what?
- Increased unorganized bone matrix density causes them to be more brittle.
- Predisposed to infections.
- Compression on nerve roots creates nerve palsies.
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What are some acquired diseases of bone development?
- Osteoporosis
- Paget disease (osteitis deformans)
- Hyperparathyroidism
- Osteomyelitis
- Fibrous Dysplasia
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Osteoporosis:
What is it?
Who is affected? hormonal affects?
Most common sites of osteoporotic problems?
- Increased porosity of the skeleton resulting from REDUCED bone mass: increased bone FRAGILITY
- Postmenopausal females, associated with reduced estrogen. (most affected)
- Older men because of lower androgen levels w/ age
- Older people bc of reduced physical activity.
- Most common sites include vertebral bodies, pelvis, femoral neck and other WEIGHT bearing bones.
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What are the causes of primary vs secondary Osteoporosis?
- Primary: (most common) associated with aging, decrease in hormones/activity.
- Secondary: (Generalized) dude to a wide variety of pathoses. Endocrine disorders, neoplasia, gastrointestinal issues, rheumatologic disease, drugs, miscellaneous things.
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Osteoporosis:
Time of peak bone mass.
Factors influencing peak bone mass
- Peak bone mass 25-30. Decreases from there
- Physical activity, genetics and nutrition affect peak bone mass.
- Menopause and aging influence development of osteoporosis.
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Osteoporosis:
Treatment:
Prognosis:
- TX: Diet and exercise, disphosphonates, estrogen replacement or SERMS, Calcitonin, Parathyroid hormone, dietary intake of calcium and vitamin D.
- Prognosis: "Gaurded" questionable.
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Paget disease of Bone (aka?)
What is it?
overview of progression:
net effect?
- Paget disease (Osteitis deformans) Abnormal dense bone formation which is structurally weak and prone to fracture.
- Repetitive episodes of increased regional osteoclastic activity and bone resorption, followed by osteoblastic activity and bone formation, and finally by exhaustion of cellular activity.
- Net effect = gain in bone mass, but newly formed bone is disorded an lacks strength.
- Skeletal deformation caused by accumulation of excessive amounts of abnormal, unstable bone!
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Paget disease (osteitis deformans)
Age?
Monostotic vs. polyostotic?
- Affects adults over 40
- Monostotic 15% and Polystotic 85% Usually affects multiple bones. Rarely affects entire skeleton.
- Bone enlargement, pain, deformity, cranial nerve compression, bowing of bones and fractures.
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Histopathologic features of Pagets Disease (Osteitis deformans)
Mosaic pattern of bone. Radiographically, mixture of adiolucent/radiopaque areas referred to as the cotton wool pattern.
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Paget disease (Osteitis deformans)
Symptoms? key symptom of the face?
Complications?
- 80-90% are asymptomatic, most are discoved on routine radiographs.
- Symptoms variable: include enlargement, bone pain, deformity, CN compression, hearing loss and visual disturbances, bowing of bones/fractures.
- Leontiasis ossea (lion face, overgrowth of factial/cranial bones).
- Development of sarcomas (osteosarcomas).
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Paget Disease (Osteitis deformans)
3 phases:
- Osteolytic Phase: Initial increased osteoclastic activity/bone resorption.
- Mixed Phase: osteoblastic activity and bone formation.
- Osteosclerotic Phase: Finally an apparent exhaustion of cellular activity.
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Paget disease:
Diagnosis:
Treatment?
Increased rik for development of what?
- Diagnosis: initially radiographic, then check for elevated levels of urinary hydroxyproline (increased bone resorption) and serum alkaline phosphatase (increased bone apposition).
- Tx: Calcitonin, bisphosphonates, analgesics for bone pain.
- Increased risk for development of sarcomas (especially osteosarcoma).
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Hyperparathyroidism: what is it?
What does PTH do?
Net result?
- Inappropriate secretion of PTH
- PTH plays a central role in calcium homeostasis via it's effects on: Osteoclast activation, increased calcium resorption by the kidneys, and increased synthesis of vitamin D in the kidneys resulting in increased calcium absorption from the gut.
- Net result: Elevation in serum calcium level.
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What's primary and secondary hyperparathyroidism?
- Primary: due to parathyroid hyperplasia (95%), adenoma or carcinoma. Important cause of hypercalcemia.
- Secondary: Due to renal failure (most common cause), leads to poor calcium retention and altered vitamin D metabolism. It's caused by any condition associated with a chronic depression in the serum calcium level. Low serum calcium level leads to compensatory over activity of the parathyroids.
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What clinical manifestations has been traditionally associated with primary hyperparathyroidism?
painful bones, renal stones, abdominal groans and psychic moans.
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What is the treatment for primary and secondary hyperparathyroidism (they're different)
- Primary: Remove affected gland/tumor
- Secondary: Renal transplant, Vitamin D supplementation.
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Osteomyelitis
What is it?
what is it's main cause?
What are it's three normal pathways of spreading?
- Infection spreading through the medullary spaces of bone causing inflammation of the bone and marrow.
- Usually a bacterial infection.
- 1. Hematogenous spread (esp. Staph Aureus)
- 2. Direct extension from soft tissues
- 3. Direct traumatic introduction (implantation following compound fractures or surgery)
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Chronic Osteomyelitis:
Radiographic findings?
What's the treatment of osteomyelitis?
- Ill-defined areas of radiolucency develop and may be intermixed with radiopaque sequestra.
- Non-vital bone (sequestrum) surrounded by rim of new bone (involucrum).
- Tx: drainage, antibiotics, surgical debridement.
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Fibrous dysplasia: what is it?
who does it affect?
Histopathologic appearance?
- Replacement of normal bone by fibrous CT and abnormal bony trabeculae.
- Affects adolescents and young adults.
- "Chinese characters" mix of cellular fibrous CT intermixed with elongated trabeculae of immature woven bone. Looks like ground glass.
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Fibrous Dysplasia:
Monostotic fibrous dysplasia?
Polyostotic fibrous dysplasia without endocrine involvement?
Polyostotic fibrous dysplasia in association with endocrinopathies?
- Monostotic fibrous dysplasia: involves a single bone. 70% of cases. Childhood.
- Polystotic fibrous dysplasia without endocrine involvement: (Jaffe Syndrome): multiple bones affected. Involvement is unilateral. craniofacial bones. Cafe-au-lait pigments.
- Polyostotic fibrous dysplasia with endocrinopathies (McCune-Albright syndrome): least common 3%. Cafe-au-lait spots and endocrine abnormalities.
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Fibrous dysplasia treatment
Observation?
Surgical reduction?
- Observation: many will stabilize at puberty
- Surgical reduction: Usually delayed until after skeletal maturity.
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Osteosarcoma:
What is it?
Mean age of onset?
Symptoms? Characteristic feature?
Most common site?
- Mesenchymal malignancy that produces osteoid and bone.
- Most common bone cancer in children, mean age 18
- Pain and swelling of affected bone. Painful enlarging mass. Radiographic "sunburst" appearance.
- Codman's triangle is a characteristic feature. The formation of an acute angle between the neoplastic bone and cortex.
- Most common site is the knee 60%, hip 15%, shoulder 10%, face 8%
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Osteoarthritis: (aka?)
what is it?
Age related?
Systemic affect?
what does it develop from/fundamental feature?
- aka "degenerative joint disease"
- Most common joint disorder
- Age related, usually people over 50
- involvement of one or a few joints usually.
- Fundamental feature: Stems from degeneration of articular cartilage (bone changes are secondary)
- Mechanical stresses play a major role.
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What are two clinical findings of Osteoarthritic joints?
- "joint mice" fragments of dislodged bone and cartilage that float free in the joint space.
- At margins of the joint, small bony outgrowths termed osteophytes arise and help to further inflame the surrounding synovial membrane.
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Gout: what is it?
Results in (3 things)
what gender/body part is most affected?
What is the second most affected organ?
- Gout is a disease of uric acid accumulation.
- Results in:
- 1. Episodic, acute arthritis.
- 2. tophus (tophi) formation (deposits of urate crystals in articular surface which penetrate joint surface and surrounding bone)
- 3. kidney damage.
- Adult males, great toe (90%)
- Kidney is the second most affected organ (after joints): pyelonephritis, nephrosclerosis, uric acid renal stones)
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Treatment of Gout:
- Diet modification
- Colchicine, allopurinol,
- NSAIDs for pain.
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Muscular dystrophy
What is it?
Heterogenous group of heritable disease with spontaneous, progressive degeneration of muscle fibers. Vary from mild motor weaknesses to sever life-threating alterations.
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What is Duchenne Muscular dystrophy?
inheritance?
What is dystrophin?
- Most common and devastating form of muscular dystrophy.
- X-linked condition
- Caused by the absence of DYSTROPHIN a key structural protein in skeletal and cardiac muscle.
- Dystrophin: a protein that attaches muscle fibers to the cell membrane, plays an important role in the structure and function of the myocyte.
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Muscular dystrophy:
when do symptoms begin, age of onset?
symptoms?
Treatment?
- Signs usually begin by 3-5 years of age
- Weakness of pelvic and shoulder areas, progressive atrophy and deterioration of muscle.
- No treatment available, most patients in wheelchair by early teens and die before age 30 of disease related complications (pneumonia, cardiac or respiratory disease.
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Myasthenia Gravis:
Type of disease?
How is it caused?
gender predominance?
Symptoms/progression of disease?
initial presentation/symptom?
- Acquired, autoimmune disease.
- Auto antibodies produced which results in a destruction of acetylcholine receptors in the neuromuscular junction.
- manifested by weakness and prominent fatigability of voluntary muscles.
- Problems with eye muscles and muscles of mastication may be initial presentation.
- Weakness worsens with repeated contractions, symptoms worse in later days.
- Female predominance, any age, insidious onset.
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Myasthenia gravis:
Which muscles are most severly affected?
eye muscle problems?
- The most active muscles generally are the most severely affected, such as the muscles involved in eye movement, facial expression, chewing, swallowing and respiration.
- Muscle weakness becomes evident with small, frequently utilized muscles:
- eyelids (ptosis: drooping of eyelids)
- eye movement muscles (diplopia: double vision).
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Myasthenia Gravis
Treatment:
- Cholinesterase inhibitors (improves transmission by not destroying Ach), Imunosuppression, thymectomy may induce remission.
- Spontaneous remission in some cases.
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