Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine > Week 4: Metabolic Bone Disease, Osteoporosis > Flashcards

Week 4: Metabolic Bone Disease, Osteoporosis Flashcards

1
Q

Define osteoporosis

A

systemic skeletal disease characterized by

  • low bone mass
  • microarchitectural deterioration of bone tissue
  • increased bone fragility and susceptibility to fracture
  • bone mineral density (BMD) below 2.5 SD below mean peak value in young adults
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Normal bone turnover

A

each cycle consists of resting bone surface, resorption, reversal, bone formation, mineralization (3 weeks of breakdown, 3 months of formation and mineralization)

  1. osteoblasts activate osteoclasts through RANKL
  2. bone resorption for about 4 weeks in a bone remodeling unit
  3. Reversal: Apoptosis of osteoclasts, release TGF-b and IGF-1 that signal osteoblasts to lay down bone
  4. Mineralization, osteoblasts become osteocyte
    - osteocytes release sclerostin, which inhibits osteoblasts
    - when osteocytes recognize abnormal bone, it removes sclerotin signaling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Concepts behind pathogenesis of osteoporosis

A
  • bone resorption is greater than bone formation

- through each cycle of bone remodeling, there is net bone loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Non modifiable risk factors for osteoporosis

A
  1. gender: females have less bone mass and smaller skeletal dimensions than men.
  2. Race: caucasians/asians have less bone mass than Hispanics who have less than Blacks
  3. Bone geometry
  4. age: decrease of bone mass ~1%/year after 35-40yo
  5. prior history of fragility fracture: vertebral fracture increases risk 5x for another
  6. Hereditary
  7. Body weight/small stature: less than 127 lbs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Modifiable risk factors for osteoporosis

A
  1. Diet: low calcium diet
  2. Estrogen: following menopause, rapid loss of bone (perhaps due to increased RANKL, IL-1, IL-6, decreased OPG)
  3. physical activity
  4. extreme exercise: fall of estrogen production if exercise induces amenorrhea
  5. cigarette smoking
  6. alcohol abuse
  7. nuliiparity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Secondary causes of osteoporosis

A
  1. failure to develop normal skeletal mass during growth due to poor nutrition or inadequate exercise
  2. endocrine deficiency or excess
    - estrogen or testosterone deficiency
    - cushing’s: excessive glucocorticoids impairs osteoblasts
    - hyperthyroidism: high thyroid hormone causes increased bone turnover and loss. more clast less blast
    - hyperPTH
  3. immobilization or weightlessness
  4. hematologic malignancies, e.g. MM, Il1 increases clast, MP-6 inhibits blasts
  5. Glitazones for DM: fibroblasts diverted from blasts to fat
  6. inherited defects on collagen synthesis
  7. systemic mastocytosis
  8. heparin therapy: activates osteoclasts
  9. idiopathic juvenile osteoporosis
  10. bariatric surgery: malabsorption, Mg and VitD deficiency
  11. solid organ transportation: chronic illness, GCs, drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Clinical features of osteoporosis

A
  1. thoracic and lumbar vertebral fractures. Most common, many asymptomatic
  2. Femur fracture
  3. distal radius fracture
    Complications of fractures
    -acute pain, chronic back pain, loss of height, kyphosis, disability, depression, mortality following hip fracture
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Assessment of osteoporosis

A
  1. Radiology
    - spine x-ray most useful
    - doesn’t distinguish osteoporosis from osteomalacia
  2. Measurement of bone mineral density
    - gold standard: dual energy x-ray absorptiometry
  3. Serum chemistry testing
    - Ca, phosphate, alkaline phosphatase, VitD, TSH, PTH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Radiological features of osteoporosis

A

Vertebral fractures

  • early: decreased BMD
  • advanced: compression of vertebral disk, fish mouthing look
  • severe: smaller vertebral bodies
  • Schmorel’s node: protrusion of disk into vertebral body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Diagnosis of osteoporosis

A
  • T score less than -2.5 in any region.
  • osteopenia: T score between -1 and -2.5
  • for every Std Dev decline, fracture risk increases 2-3x
  • z scores are matched for age and gender and based on ethnicity, but not used for dx. T scores are of interest.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Fracture risk reduction in osteoporosis

A
  • preserve/increase BMD: Ca/VitD supplements, drug therapy (HRT, anti bone resorption)
  • Fall prevention: exercises, VitD, balance exercises
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Guidelines for osteoporosis therapy

A
  • all women with T score less than -2.5
  • all women with T score less than -1.5 with risk factors other than menopause
  • all postmenopausal women who have had a fragility fracture
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Drug therapies for osteoporosis

A
  1. Antiresorptives
    - bisphosphates: prevents release of acid for bone resorption by osteoclasts. induces apoptosis of osteoclasts
    - SERMs
    - estrogen: alter ratio of RANKL and OPG. concern for increase of Coronary heart disease and breast cancer
    - calcitonin: antiosteoclastic
  2. Anabolic agents
    - (Teraperidtide) PTH 1-34: low dose PTH stimulates osteoblasts. Requires daily subQ injections. Expensive. May case hypercalcemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Side effects of oral bisphosphonates

A
  • upper GI distress
  • flu-like syndrome
  • osteonecrosis of jaw: super rare
  • no increase in A fib
  • frozen bone/atypical fractures: can’t repair minor bone injury due to inhibited osteoclast activity -consider a drug holiday
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Zolendronic acid

A
  • once a year IV infusion
  • side effects: severe flu like symptoms, increase in Cr
  • no increase in A fib, and no osteonecrosis of jaw
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define osteomalacia and rickets

A
  • usually due to Vit D deficiency or phosphorus deficiency
  • characterized by inadequate mineralization of bone collagen
  • radiology: decreased density of bone-looks like osteoporosis
  • Rickets: in children, growth retardation and widening of epiphyses
17
Q

Causes of Vitamin D deficiency

A
  • inadequate sunlight exposure or impaired cutaneous production
  • extensive use of sunscreen
  • poor dietary intake
  • malabsorption: gastrectomy, sprue, small intestinal disease, pancreatic insufficiency
18
Q

Disorders of Vitamin D metabolism

A
  1. Accelerated loss of Vitamin D
    - increased metabolism
    - impaired enterohepatic recirculation
    - nephrotic syndrome
  2. Impaired 25 hydroxylation
    - liver disease, isoniazid
  3. Impaired 1a-hydroxylase
    - renal failure, ketoconazole
  4. target organ resistance
19
Q

Causes of phosphate deficiency

A
    1. decreased intestinal absorption
  • decreased intake
  • Al2(OH)2 excess (antacid)
    1. X linked hypophosphatemia rickets
    1. autosomonal dominant hypophosphatemic rickets
      1. hereditary hypophosphatemic rickets with hypercalcuria
      2. Fanconi
    1. Tumor induced osteomalacia
20
Q

X linked hypophosphatemia rickets

A

Normal
-Phosphatonin (FGF-23) is released from bone and inhibits Na/Phosphate transporter in kidney. It is excreted instead of reabsorbed.
Disease
-PHEX gene is mutated. Lack of ability to degrade phosphatonin
-renal phosphate wasting
-most common cause of rickets in US

21
Q

Autosomonal dominant hypophosphatemic rickets

A
  • activating mutation of FGF23. PHEX is unable to break down this mutated FGF23.
  • incomplete penetrance
  • may have delayed onset of disease
22
Q

Tumor induced osteomalacia

A
  • mesenchymal tumors
  • usually in adults
  • sporatic, acquired
  • tumor produced FGF23 acts on proximal tubule to decrease phosphate transport and decrease active Vit D synthesis
23
Q

Clinical features of osteomalacia

A
  • may have no symptoms in mild cases
  • bone pain
  • muscle weakness and pain
  • reduced BMD
  • fractures, pseudofractures (stress fractures)
  • symptoms of hypocalcemia in severe Vitamin D deficiency
24
Q

Clinical features of rickets

A

Short stature
Deformities of lower extremities (also upper extremities but less so): bow leg
Swelling of wrists (epiphysis)
Rachitic rosary (swelling of cartilage-bone junction)-costochondral junction
Skull deformities: frontal bossing, flattening of skull
Bone pain
Cupping and fraying (inadequate mineralization of bone) of diaphysis and epiphysis
Symptoms of hypocalcemia if due to severe vitamin D deficiency

25
Q

Radiographic features of osteomalacia

A
  • osteopenia
  • pseudofractures
  • biconcave vertebrae
  • deformed pelvis
  • protrusio acetabuli
26
Q

Evaluation of osteomalacia

A
  1. Labs
    - serum Ca: normal to low in Vit D def. (VDD), normal in XLH, TIO
    - phosphate: normal to low in VDD, low in XLH and TIO
    - alk phos: high in all (released by osteoclast)
    - PTH: high in VDD, normal in XLH, TIO
    - 25(OH)D: low in VDD< normal XLH, TIO
    - 1,25(OH)2D: normal to low in VDD, normal in XLH, low in TIO
    - TmPO4 (tubular maximum for phosphate): low in all
    - FGF23: normal in VDD, high XLH, TIO
    - xrays

Endocrine (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions