Metabolic Bone Diseases: 1 Flashcards

1
Q

Metabolic bone diseases

5

A
  1. Osteoporosis
  2. Paget disease of the bone
  3. Osteomalacia
  4. Rickets
  5. Renal osteodystrophy
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2
Q
  1. What is the most common bone disease in the US?

2. Osteoporosis PP?

A
  1. Most common metabolic bone disease in the US
  2. Imbalance of bone homeostasis
    - Bone resorption (osteoclast activity) outpaces bone deposition (osteoblast activity)
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3
Q

Bone remodeling: Continuous process and regulated by 2 control loops. Describe these? 2

A
  1. Negative feedback loop
    - Hormonal process that maintains calcium homeostasis
  2. Stress on the skeleton
    - Mechanical
    - Gravitational
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4
Q

Describe the hormonal control of bone homeostasis with PTH

3 steps

A
  1. Decrease in plasma calcium
  2. Release of PTH from the parathyroid
  3. Kidney, bones, GI
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5
Q

Effects of PTH

  1. Kidney? 2
  2. Bone? 2
  3. GI tract? 1
A
    • ↑ Ca resorption in the renal tubules
    • Kidneys convert Vit D to it’s active form
    • ↑ osteoclast activity
    • Release Ca2+ and PO4-
  1. GI tract ↑ absorption of Ca2+, PO4-
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6
Q

What is responsible for bone reabsorption?

A

Osteoclast activity

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7
Q

Osteoclast activity

Stimulated by? 4

A
  1. PTH,
  2. Calcitonin,
  3. GF IL-6
  4. Lack of gonadal hormones
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8
Q

Osteoclast activity

Lack of gonadal hormones affects the body how? 2

A
  1. Increased activity, vigor and lifespan of clasts

2. Low estrogen increases IL-6

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9
Q

Osteoblast activity

  1. Affect bone matric how?
  2. How do osteoblasts change with age?
A
  1. Builders of bone matrix

2. Decreased number of osteoblasts with aging

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10
Q

Thyroid gland: can stimulate or inhibit osteoclast activity

  1. How would it increase?
  2. Decrease it?
A
  1. Hyperthyroidism
    - Thyroid hormones can stimulate osteoclast activity
  2. ↑ plasma calcium
    - Thyroid gland releases calcitonin
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11
Q

Hormonal control of bone homeostasis with Ca? 3 steps

A
  1. Increased Ca2+
  2. Calcitonin released from the thyroid
  3. Kidney, bones, GI tract
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12
Q

Effects of calcitonin

  1. Kidney? 2
  2. Bones? 2
  3. GI? 1
A
    • ↓Ca2+ absorption
    • ↓PO4- absorption
    • ↓ osteoclast activity
    • ↓ release of Ca2+
  1. ↓ Ca2+ absorption
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13
Q
Risk factors (major categories) OP
9
A
  1. Age (≥ 50 years old)
  2. Gender (female)
  3. Race (white or Asian)
  4. Activity level (inactivity)
  5. Diet
  6. Hormonal
  7. Meds
  8. Family history
  9. Medical history
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14
Q

Dietary risk factors for OP? 3

A
  1. ETOH
  2. Tobacco
  3. Low calcium intake or altered ability to absorb
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15
Q

Hormonal risk factors for OP? 6

A
  1. Amenorrhea
  2. Late menarche
  3. Early menopause
  4. Post menopausal state
  5. Low testosterone
  6. Low estrogen
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16
Q

Medical conditions that may be associated with osteoporosis

9

A
  1. Rheumatologic conditions (Lupus, RA, others)
  2. Malabsorption syndromes
  3. Hypogonadism
  4. Hyperthyroidism
  5. Chronic kidney disease
  6. Chronic liver disease
  7. COPD
  8. Hyperthyroidism
  9. Neurologic disorders
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17
Q

Meds that put you at risk for OP?

12

A
  1. Heparin
  2. Warfarin +/-
  3. Cyclosporine
  4. Medroxyprogesterone acetate (Provera)
  5. Vitamin A
  6. Loop diuretics
  7. Chemotherapeutic drugs
  8. Antiseizure meds
  9. Proton pump inhibitors
  10. H2 Blockers
  11. Antidepressants (TCA’s and SSRI’s)
  12. Glucocorticoids (STEROIDS)
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18
Q

Mnemonic
OSTEOPOROSIS
12

A
  1. LOw calcium intake
  2. Seizure meds
  3. Thin build
  4. ETOH
  5. HypOgonadism
  6. Previous fracture
  7. ThyrOid excess
  8. Race (white, Asian)
  9. Other relatives with osteoporosis
  10. Steroids
  11. Inactivity
  12. Smoking
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19
Q

Prevention of osteoporosis

5

A
  1. Exercise (weight bearing and muscle strengthening)
  2. Appropriate vitamin D and calcium intake
  3. Cessation of tobacco use
  4. Avoidance of excessive alcohol intake
  5. Screening tests: Measure height, DXA
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20
Q

Standard test for the evaluation of bone mineral density?

A

DEXA (DXA) scan

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21
Q

DEXA scan: Max weight for the machine?

A

300 pounds (some newer machines support up to 400 pounds)

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22
Q

DEXA (DXA) scan indications

3

A
  1. Anyone currently being treated or considering pharmacologic therapy for osteoporosis
  2. Anyone not receiving therapy in whom evidence of bone loss would lead to treatment
  3. Screening for osteoporosis
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23
Q

DEXA (DXA) scan: Screening guidelines

5

A
  1. All women ≥ 65 and men ≥ 70 regardless of risk factors
  2. Younger postmenopausal women and men (50-70 years) with risk factors
  3. Adults with fragility fractures
  4. Adults who have a condition associated with low bone mass (rheumatoid arthritis)
  5. Adults who take medications associated with bone loss (steroids)
24
Q

What is your T score?

A

Bone mineral density compared to what is normally expected in a young healthy adult (at their peak BMD) based on gender.

25
Q
  1. Osteopenia T score?
  2. Osteoporosis?
  3. Severe osteoporosis?
A
  1. -1 to -2.5
  2. Less than -2.5
  3. Less than -2.5 plus fragility fracture(s)
26
Q

Z-score is different than the T-score

Used in the following populations? 3

A
  1. Premenopausal women
  2. Men younger then 50 years
  3. Children
27
Q

Z score

  1. -2.0 or lower?
  2. Above -2.0?

Dx of osteoporosis in this group should not be based on BMD results alone

A
  1. -2.0 or lower
    defined as “below the expected range for age”
  2. Above -2.0
    “within the expected range for age”
28
Q

Quantitative calcaneal ultrasonography

  1. Effective at predicting what?
  2. Advantages? 3
  3. Used for what?
A
  1. Effective at predicting
    - femoral neck,
    - hip and
    - spine fractures
    • Lower cost than DXA
    • Portable
    • No exposure to radiation
  2. Used as a screening test not for diagnosis of osteoporosis
29
Q

Screening: Vertebral imaging (NOF recommendations)
1. If bone density testing is not available? 2

  1. Consider in patients with T-score -1.5 in? 3
A
  1. If bone density testing is not available
    - All women ≥ 70
    - All men ≥ 80
  2. Consider in patients with T-score -1.5
    - Women 65-69
    - Men 75-79
    - Once the initial test is done repeat if suspect new vertebral fracture, loss of height or new back pain or postural change
30
Q

When should you repeat the vertebral imaging? 4

A

repeat if suspect

  • new vertebral fracture,
  • loss of height or
  • new back pain or
  • postural change
31
Q

Screening: Vertebral imaging (NOF recommendations)

6

A
  1. Postmenopausal women 50-64 and
  2. men 50-69 with specific risk factors
  3. Low trauma fx,
  4. historical height loss of 1.5” or more,
  5. prospective height loss of 0.8” or more,
  6. recent or ongoing long term glucocorticoid treatment
32
Q

Osteoporosis Work up

5

A
  1. History
  2. Physical exam
  3. Lab
  4. +/- X-rays
  5. DXA scan
33
Q

OP Hx questions?

4

A
  1. Include questioning to determine if there is any history of disease that may affect bone metabolism
  2. Family history
  3. Any history of low vitamin D, prior bone density testing, prior fractures
  4. Medication review
34
Q

OP signs and symptoms? 3

A
  1. Usually asymptomatic unless there is a fracture.
  2. Gradual loss of height
  3. Dowager’s hump
35
Q

OP Work up continued: Lab

8

A
  1. CBC
  2. CMP
  3. Serum magnesium
  4. TSH
  5. 25-OH Vitamin D
  6. PTH
  7. Testosterone (in younger men)
  8. 24 H urine calcium
36
Q

Work up: X-rays

  1. For who?
  2. In asymptomic pts with?
  3. Cannot be used to dx?
A
  1. In symptomatic patients
  2. In asymptomatic patients if a vertebral fracture is suspected (or recent loss of height)
  3. Cannot be used to diagnose osteoporosis but can suggest osteopenia
37
Q

Nonpharmacologic Treatment

3

A
  1. Calcium
  2. Vitamin D
  3. Exercise
38
Q

Ca2+
1200 mg daily (from diet and supplements)
SE? 4

A

Side effects

  1. Nephrolithiasis
  2. Dyspepsia
  3. Constipation
  4. Interfere with the absorption of iron and thyroid hormone
39
Q

Calcium citrate vs. calcium carbonate

  1. Calcium citrate when?
  2. Also less likely to cause what?
A
  1. When concomitant use of acid suppressing meds (H2 blockers and PPIs)
    - Citrate is better absorbed
  2. Citrate may be less likely to cause kidney stones
40
Q

Vitamin D
800 IU vitamin D3 supplementation daily is recommended
SE? 3

A

May need more if initial vit D levels are low

Side effects
Excessive vit D levels can cause 
1. hyperpcalcemia, 
2. hypercalciuria, 
3. kidney stones
41
Q

NOF 2014 guidelines for pharmacologic treatment

6

A
1. Age 50 and older
and
2. Hip or vertebral fracture
or
3. T-scores 
≤ -2.5 (measured at femoral neck, total hip or lumbar spine)
  1. T-score
    - 1.0 to -2.5 in postmenopausal women and men age 50 and older
  2. Plus 10 year hip fx probability ≥ 3%
  3. or a 10 y major osteoporosis fracture probability of ≥ 20%
42
Q

Pharmacologic options for treatment of osteoporosis

7

A
  1. Bisphosphonates
  2. Calcitonin
  3. Estrogen agonist/antagonist (raloxifene, Evista)
  4. Hormone therapy
  5. Parathyroid hormone 1-34 (teriparatide)
  6. RANKL inhibitor (denosumab)
  7. Tissue selective estrogen complex (conjugated estrogens/bazedoxifene, Duaveetm)
43
Q

Bisphosphonates

Which drugs are these? 4

A
  1. Alendronate (Fosamax)
  2. Risedronate (Actonel)
  3. Zoledronic acid (Reclast)
  4. Ibandronate (Boniva)
44
Q

Bisphosphonates: Mechanism of action

Bisphosphonates
a
Half life: 
1. In plasma?
2. In bone?
A

Inhibit bone resorption by decreasing the number and function of osteoclasts

Half Life

  1. In plasma: 1 hour
  2. In bone: may persist for a lifetime
45
Q

Bisphosphonates: Pharmacokinetics

  1. Absorption?
  2. Cleared?
  3. Remaining amount taken up by?
A
  1. Only 1-5% of the oral dose is absorbed
  2. 70% of the absorbed dose is then cleared renally
  3. The remaining 30% is taken up by the bone
46
Q

Bisphosphonates: pretreatment screening and testing

6

A
  1. GFR needs to be > 30-35 ml/min
  2. Correct calcium and vitamin D deficiencies prior to administration
    25 OH Vit D levels should be > 25-30 ng/ml (62-75 nmol/L)
  3. Review history and symptoms for any abnormalities of the esophagus (stricture or achalasia) or delayed gastric emptying
  4. Ability to remain upright for 30-60 min post oral dose
  5. Recent fracture (wait 4-6 weeks to start rx)
  6. Plans for dental extractions or implants?
    - May increase risk for osteonecrosis of the jaw
47
Q

Oral bisphosphonates: contraindications

4

A
  1. Barrett’s esophagus
  2. Active upper GI disease
  3. DC if symptoms of esophagitis occurs
  4. If GFR is not greater then 30-35 ml/min
48
Q

Aldronate (Fosamax)

  1. Advanatges? 3
  2. Take how often?
A
  1. Generic, low cost
  2. Greater increase in BMD then Actonel at all sites after 12 months of therapy
  3. Well tolerated and effective for 5-10 y

No difference in incidence of 2
-Daily or weekly

49
Q

Risedronate (Actonel)

  1. Advantage? 2
  2. How often?
A
  1. May have less GI side effects
  2. Well tolerated and effective for up to 7 y

Daily, weekly or monthly

50
Q

What are the IV therapy biphophanates? 2

When would you use these? 2

A
  1. Zoledronic Acid 5mg/year
    (Reclast)
  2. Ibandronate (Boniva)
  3. If cannot tolerate oral therapy or if failure to respond to oral therapy
  4. No evidence that it decreases hip fracture
51
Q

Bisphosphonates: Side effects

A
  1. GI
  2. Hypocalcemia (more common with IV)
  3. Musculoskeletal pain
  4. Ocular
  5. Atypical fracture
  6. Osteonecrosis of the jaw
  7. Flu-like symptoms post IV infusion
52
Q

Bisphosphonates: Side effects

GI? 3 (possibly 4)

A
  1. Reflux,
  2. esophagitis,
  3. ulcers
  4. Esophageal cancer(?)
53
Q

Biphosphanates Ocular SE?
5

What kind of atypical fxs? 2

A
  1. Eye pain,
  2. blurred vision,
  3. conjunctivitis,
  4. uveitis,
  5. scleritis
  6. Subtrochanteric
  7. Lateral
54
Q

Bisphosphonates side effects: Osteonecrosis of the jaw
Risk Factors?
8

A
  1. IV bisphosphonates
  2. Anticancer therapy
  3. Dental extractions
  4. Dental implants
  5. Poorly fitting dentures
  6. Glucocorticoids
  7. Smoking
  8. Pre-existing dental disease
55
Q

Bisphosphonates:
Duration of therapy
1. Aldronate (Fosamax) and Risedronate (Actonel)
-When do you reassess need?

  1. When would you d/c therapy?
  2. When would you continue it?
A
  1. 5 years
  2. Low risk, no fractures, T score > -2.5 may consider discontinuation of therapy
  3. High risk, T score ≤ -3.5 continue therapy for up to 10 years
56
Q

Estrogen agonist/antagonist (SERMs): Raloxifene (Evista)
1. Indicated for?

  1. Less effective then?
A
  1. Indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
  2. Less effective than estrogen and bisphosphonates
57
Q

Raloxifene (Evista)

  1. Dose?
  2. SE? 3
A

60mg once daily

Side effects:

  1. DVT,
  2. hot flashes,
  3. endometrial cancer