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Flashcards in Bone 1 Deck (30):
1

Stages of Callus formation

Hematoma Stage- hours to days
Inflammatory Stage-within 48hrs
Granulation Tissue-2-12 days
Soft Callus- one week-several months
Hard callus-one week-several months
Remodeling-several months

2

What are common osteoporotic fracture sites?

proximal humerus
spinal compression fractures
hip fractures
distal radius

reduction in trabecular bone mass despite normal bone mineralization

3

Primary osteoporosis type 1 vs 2

Primary osteoporosis
Type 1
-postmenopausal, increase of bone resorption due to estrogen decrease
Type 2
-senile osteoporosis: affects men and women 70 y/o (age related calcium deficiency)

4

How does menopause lead to osteoporosis?

1. decreased serum estrogen
2. increased IL1,IL6, and TNF levels
3. Increased expression of RANK, RANKL
4. Increased osteoclast activity

5

How does aging lead to osteoporosis?

1. decreased replicative activity of osteoprogenitor cells
2. decreased synthetic activity of osteoblasts
3. decreased biologic activity of matrix-bound growth factors
4. Reduced physical activity

6

Secondary Osteoporosis Causes

1. Endocrine
Hyperthyroidism
-accelerated turnover of bone and increased osteoclastic activity
Hypogonadism
-woman-estrogen
men-anabolic androgens
Hyperparathyroidism
-osteoclast recruitment and increased osteoclastic activity

2. Drugs
Corticosteroids
-Inhibit osteoblastic activity (suppression expression)
Alcohol
-direct inhibitor of osteoblast, may inhibit calcium absorption

3. Gastrointestinal
Malnutrition
Malabsorption
-impaired absorption of calcium, phosphate and vitamin D

4. Neoplasia
Multiple Myeloma
-Secretion of osteoclast activating factor

7

What are the symptoms of osteoporosis? What does it look like on xray/labs?

Fractures
Vertebral Fractures
Pain
Additional complication: pulmonary embolism, pneumonia

NOT detectable on x ray until 30-40% bone mass lost
Blood Calcium, Phosphorous, alkaline phosphatase levels NOT diagnostic

8

Bone densitometry-dual energy xray absorptiometry (DEXA) scans measure what

bone thickness/density at different parts of the body
-two x ray beans of different energy levels

9

WHat is the bone mineral content of of a normal, osteopenia, osteoporosis patient?

Normal: Bone mineral content not more than 1 SD below the young adult mean (T score above -1)

Osteopenia: Bone mineral content between 1SD and 2.5SD below the young adult mean (T score between-1 to-2.5)

Osteoporosis: Bone mineral density 2.5 or more below the young adult mean (T-score at or below -2.5)

10

What are the indications for bone density test?

1. woman 65 regardless additional risk factors

3. Estrogen deficient women at risk for low bone density

4. Patient treated with glucocorticoids

5. patients with asymptomatic primary or secondary hyperparathyroidism

11

What are treatments/prevention for osteoporosis?

1. exercise
2. calcium and vitamin D
3. bisphosphonates
4. estrogen replacing agents
5. recombinant PTH
6. RANK ligand inhibitor (denosumab)

12

Rickets/Osteomalacia

Etiology=vitamin D deficiency
Bone mineralization defect
Accumulation of osteoid (unmineralized bone, soft bone)

13

Osteomalacia-Adults

Loss of skeletal muscle mass(density)-osteopenia
Fractures and microfractures
-vertebral bodies and femoral neck
Bone pain
lots of osteoid

14

Rickets-children
Pathology
Symptoms
Treatment

Excess unmineralized bone-growing bones
-growth plate not adequately mineralized
-osteoclasts do not resorb growth plate cartilage
-growth plate irregular, thickened, lobulated
-loss of structural rigidity of bones

Symptoms :
1. Bowing of legs
2. Rachitic Rosary-osteoid deposition at the costochondral junction
3.Pigeon Breast Deformity-inward bending of ribs with anterior protrusion of the sternum
4. Occipital bones flattened
5. Parietal bones buckled
6. Frontal bossing (enlarged forehead)/squared appearance of head

How common:
very common!

Treatment:
vitamin D

15

Hyperparathyroidism are causes of primary and secondary hyperparathyroidism?

Increased parathyroid hormone level
Primary: Adenoma, Hyperplasia, Carcinoma
Secondary: Prolonged hypocalcemia stimulates PTH hypersecretion

16

Hyperparathyroidism results in increased PTH what does this do?
What are the symptoms

1. sensed by osteoblast receptors
2. release mediators of osteoclastogenesis
3. increased osteoclast activity
4. bone resorption

1. decreased bone mass
2. pain
3. fractures-stress fractures

17

How does this hyperparathyroidism appear histologically?

dissecting osteitis
railroad tracks

18

What type of tumor can hyperparathyroidism lead to?

brown tumor

19

What is osteitis fibrosa cystica?

hyperparathyroidism
-bone replaced with fibrous tissue and cystic change

20

Paget's disease
Etiology
Histology

Disease caused by osteoclast dysfunction
-characterized by excessive breakdown of bone tissue followed by abnormal bone formation
-affecting MEN 2:1
-mid adulthood
-axial skeleton, proximal femur involved up to 80% of patients

Etiology:
1. slow virus infection
-Paramyxovirus (remains hypothesis)
-Induces IL6 secretion, increased RANK expression
-stimulates osteoclast activity
2. Genetic
-gene mutation leading RNK mediated osteoclast stimulation
-Mutations in RANKL and RANK/OPG

Histology:
1. mosaic pattern of bone -prominent cement lines


21

What are the three stages of Paget Disease?

1. Osteolytic (osteoclasts)
2. Osteolytic-osteoblastic (mixed osteoclasts + osteoblasts)
3. osteosclerotic (osteoblasts)

22

what are the symptoms of paget's disease? HOw do you diagnosis it?

Symptoms:
1. Pain in affected bones
-microfractures
-bone overgrowth compressing nerves, spinal roots
2. Platybasia-flattening of the skull base impinging on foramen magnum
3. Leontiasis ossea
4. secondary arthritis
5. thickening of skull
6. bowing of tibia




23

What can paget's disease lead to?

1. High output cardiac failure
-hypervascularity of Pagetic bones-polyostotic-increased blood flow
-elevated resting cardiac index beyond normal range 2.5-4 L/min per m2

2. Sarcoma
-5-10%
-osteosarcoma, fibrosarcoma

24

HOw do you diagnosis it?WHat are the labs in paget's disease f

Diagnosis:
radiographs-bone scan-increased osteoblast activity

Labs:
elevated serum alkaline phosphatase
-serum calcium , phosphorus unaffected

25

What is the treatment of paget disease?

Acetaminophen Nsaids
Bisphosphonates- (induce apoptosis of osteoclasts)
Calcitonin-(inhibits osteoclast function)

26

Osteogenesis Imperfecta
Defect
Symptoms
Goals of treatmetn

brittle bone disease
Defect in extracellular structural protein
-type 1 collagen (mutation for the alpha 1 and alpha 2 chains of the collagen molecule)

Symptoms:
1. Too little bone
2. Hearing loss
3. Dental imperfection (blue yellow-teeth)
4. blue sclera

Treatment
1. maximize mobility/function
2. minimize fracture risk
3. pain control
4. psychosocial

27

What are the types of osteogenesis imperfecta?

Type 1-mildest form
-autosomal dominant
Type 2-lethal, perinatal disease
-autosomal recessive
Type 3- progressive, most severely deforming type
-usually autosomal dominant
Type 4-similar to type 1 (normal sclerae)
-autosomal dominant

28

Achondroplasia

-Most common disease of growth plate
---Dwarfism
-Autosomal dominant
-80% new mutations
-failure of longitudinal bone growth (endochondral ossification)-short limbs
-membranous ossification not affected-large head


Defect in signal transduction system-Mutation in FGF receptor 3
1. Activating mutation of FGFR3
-FGFR3 normally inhibits cartilage proliferation
2. constant activation
3. Inhibits chondrocyte differentiation and proliferation
4. Retards growth plate development

29

Osteonecrosis (avascular necrosis)

bone death (infarction)
-bone and bone marrow
Gross: subchondral wedge shaped pale yellow area
Histology:dead bone-empty lacunae
Pathogenesis: Ischemia-Mechanical, corticosteroids, thrombosis/embolism, vessel injury(vasculitis, radiation), vascular compression
Etiology: trauma, corticosteroids, infection dysbarism, radiation therapy, connective tissue disorders, sickle cell anemia, tumors, pregnancy, gaucher disease, idiopathic

30

What causes osteonecrosis of the Jaw?

high dose IV disphosphonates
Predisposing factors: dental disease, dental surgery, periodontitis, poor dental hygiene, treatment with chemo or corticosteroids