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3154 MSK > osteo > Flashcards

osteo Flashcards

1
Q

osteoporosis definition

A
  • Metabolic bone disease characterised by:
    ○ Low bone density
    ○ Microarchitecture disruption (impaired mineralisation)
    ○ Decr bone strength
    ○ Incr risk of #
  • Decr in bone mass:
    ○ Excess bone resorption
    ○ Decr bone formation

porous bone

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2
Q

pathophysiology of osteoporosis

A
  • decr bone formation (osteoblast)
  • RANKL released, bone resorption (osteoclast)
  • incr bone resorption (osteoclast)
    * secrete lysosomal enzymes, HCl
    * release Ca, PO4 into bloodstream
  • hormones
    * PTH: resorption to incr Ca
    * calcitonin: inhibit resorption, decr Ca release
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3
Q

cells involved in osteo

A
  • osteoclast (break down) – activated by RANKL
  • osteoblast (growth) – sclerostin inhibits growth factor
  • osteocyte (release RANKL and sclerostin <– PTH affects)
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4
Q

osteoporosis risk factors

A
  • Post-menopausal women (low estrogen)
  • Men ≥ 65yo
  • low serum Ca, malnutrition (<500mg/d)
    * bariatric surgery, eating d/o
  • alcohol consumption (incr RANKL - resorption/ incr oxidative stress & osteoblast)
  • smoke (incr RANKL, osteoblast)
  • physical inactivity (decr bone mass)
  • previous fragility #, hx of falls
  • low body weight, height loss (> 2cm/ yr)
  • fam hx
  • med use (long-term CS, immunosupp)
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5
Q

glucocorticoids cause 2nd osteoporosis

A

CG affect the function and numbers of the 3 major bone cell types

  • induce decr in osteoblast differentiation (less bone formation)
  • increase apoptosis of both osteoblasts and osteocytes (less formation )
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6
Q

med assoc w/ osteoporosis

A

○ Prolonged systemic CS
○ Abx: FQ
○ Antiseizure: CBP, PB, PT
○ PPI
○ GnRH agonist/ antagonist
○ heparin
○ chemo immunosuppressant
○ breast cancer therapies (decr estrogen)

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7
Q

secondary causes of osteoporosis

A
  • endocrine diseases
    * menopause
    * cushing
    * eating disorder
    * hyperPTH, hyperTHY
    * DM
    * CKD-BMD
    * hypogonadism
  • GI/ nutritional disease
    * alc liver disease, severe liver disease
    * IBD
    * pancreatic insuff
    * vit D, Ca deficiency
  • marrow-related disease
    * hemophilia, leukemia, lymphoma, sickle cell anemia
  • organ transplant, immunosupp
    * bone marrow, heart, kidney, lung, liver
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8
Q

osteo self assessment tool OSTA (post menopausal women)
(need for BMD screen)

A

age (yrs) - weight (kg)

  • High risk >20
    ○ Consider DXA scan, see if low BMD
  • Medium risk 0-20 + other risk factors present
    ○ Consider DXA scan
  • Low risk <0
    ○ Defer DXA
    ○ Consider if high risk: sig. weight loss etc
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9
Q

BMD testing

A
  • post menopause women
  • men > 65yo
  • high OSTA score >20
  • Where is scanned: (Based dx on the lower value)
    ○ Hip BMD: predictive of potential # risks
    ○ Spine BMD: assess tx response
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10
Q

BMD score
Z vs T

A
  • T-score: compare to young adult ref pop
    • How many SD lower than young pop
    • T score: -1SD is reasonable due to aging
  • Z-score: compare BMD with pt age and sex
    • Will usually have a better scoring
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11
Q

3 T-scores

A

T score ≤ -2.5 SD = osteoporosis
T score -1 to -2.5 SD = osteopenia
T score ≥ -1 SD = normal BD

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12
Q

Fracture risk assessment tool (FRAX)

A
  • Consider starting anti-osteoporosis tx if 10 yr probability high.
    ○ Major osteoporotic # ≥20%
    ○ Hip # ≥3%
  • Risk factors are Country specific
    ○ Previous # (vertebral, hip)
    ○ Smoke, alcohol, CS
    ○ RA
    ○ BMD
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13
Q

osteoporosis presentation

A
  • Asx
    • Often undx until presented with fragility fracture
      ○ Low impact trauma leading to # in pts
      ○ Fall from standing height/ lower
    • Spine (vertebral compression)
      ○ Height loss
      ○ Kyphosis (curved spine)
      ○ Hip (neck of femur)
      ○ Wrist (Colles) – from breaking the fall
      ○ Humerus
      ○ Pelvis (wing, sacrum)
  • # give rise to: pain & disability
    • Incr healthcare cost, nursing home placement, mortality incr (HAI)
    • Indirect cost: hire helpers, caregiver taking leave
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14
Q

When to start tx

A
  • Pt with fragility #
    * vertebral, hip, wrist, humerus, rib, pelvis
    * spontaneous/minor trauma
    * Asx vertebral # (> 20% decr in height)
  • Pt without fragility # but DXA BMD T-scores ≤-2.5
  • Osteopaenic (DXA BMD T-score -1 ~ -2.5) & no fragility # & high FRAX, potential #
    * > 3% hip #
    * ≥ 20% major orteoporotic #
  • 2nd causes of bone loss (clinical hx, PE, labs)
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15
Q

osteo tx plan

A

1) lifestyle + diet (Ca, Vit D, exercise) = osteopenia
2) antiresorptive agents - osteoporosis

bisphosphonate (first line)
RANK ligand inhibitor (renal)
estrogen agonist (postmeno)
calcitonin
anabolcic – PTH therapy, sclerostin inhibitor

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16
Q

goals of tx

A

1) Prevent fractures — BMD as a marker (reduction in potential # risk)
2) Improve QOL
3) Reduce economic burden

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17
Q

factors to consider when decide to tx

A
  • fracture risk (high)
  • past fracture
  • BMD ( T score < -2.5)
  • age (>65yo)
  • risk for falls/ bone loss (FRAX)
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18
Q

vit D and bone metabolism

A

low lvl of vit D –>decr Ca absorption

incr PTH secretion
- Ca reabsorption from renal distal tubule
- Ca reservoir of bone depleted to correct low Ca absorption in gut

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19
Q

Bisphosphonates MOA
Risedronate, Alendronate

A

Slow bone loss by incr osteoclast cell death

bone growth > resorption

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20
Q

bispho ADMIN PO

A

Risedronate, Alendronate (PO)
- Once a week (R, A)
- Once a mnth (R)

Take Oral on empty stomach with at least 240mL of plain water
Wait >30mins before taking food
Do not lie down after meds

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21
Q

alendronate dose

A

70mg once per week (same day)

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22
Q

bispho IV admin

A

Zoledronic acid (IV: 5mg 30min infusion per yr)
Once a yr (15-30mins via cannula vein)

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23
Q

bispho tx indication and duration

A

FIRST LINE (generic avail $)
Tx for > 5yrs can extend to 10yrs
* Unless FRAX > 20% can continue tx
* But if haven’t achieve goal BMD, pt not responding
* Switch drug, decr exposure to ADR

24
Q

bispho SE

A
  • Atypical femoral fractures
  • Severe bone, joint, muscle pain
  • Upper GI mucosa irritation
  • Ocular effects (iritis, uvetitis)
  • HYPOCa (stop recovery of Ca from bone)
  • Osteonecrosis of jaw, external auditory canal
    ○ Blood supply to bone decr

PO: ND, ab pain, reflux, MSK aches
IV: flu-like sx (fever, tired, headache, hypoCa)

25
Q

ONJ risk factors

A

□ Comor (anemia, cancer, coag, preexist dental infection)
□ DDI (chemo, CS, denosumab, angiogenesis, bisphos)
□ Invasive dental procedure
□ Hx cancer, radiography
□ Poor oral hygiene

26
Q

ONJ counsel

A

□ Avoid cariogenic foods
□ Dental hygiene (brush, floss)
□ Smoking cessation
□ Complete dental before start tx (mnths until fully healed)

□ if develops ONJ during tx
* Consult dental surgeon
* Stop bisphosphonate + oral surgery

27
Q

atypical femoral # risk

A

Discontinue as it can affect bone healing

  • If pt has fragility # when to initiate bisphosphonate??
    • 1-2 wk or 3-4wk ltr/ when pt is able to sit upright
  • If pt develop fragility # even when on bisphosphonates
    • Check for underlying reason, 2nd causes, other risk factors, pt admin technique
    • discontinue based on risk-benefit (pt may be at risk of more #)
28
Q

CI for bispho

A
  • HypoCa
  • Abnormalities in oesophagus (delay emptying)
  • Reflux oesophagitis
  • Preg, lactation

IV: Vit D def – replete before infusion

29
Q

caution in bispho

A
  • Active upper GI disease
  • Risk factor for developing osteonecrosis of jaw or ext auditory canal
  • Severe renal impairment
    • (PO) Crcl <30mL/min
    • (IV renal worsens) Crcl < 35mL/min
30
Q

monitor for bispho

A
  • Ca levels (2.2-2.7mmol/L)
  • vit D levels (≥20-30 ng/mL but < 50-100ng/mL)
  • CrCl, Ca, PTH
  • BMD every 2 yrs
  • SE: esophageal/ GIT discomfort, bone pain
31
Q

duration of bispho

A
  • 3yr (IV), 5yr (PO)
    * BMD stable
    * no previous fragility #
    * # risk low FRAX
  • Extend if:
    * high # risk FRAX score
  • Restarted after 2yr (BMD decr > 4 - 5% / tx criteria met again)
    * High # risk T-score < -3%: 6yr (IV), 10yr (PO)
32
Q

RANK ligand inhibitors MOA

A

Denosmab
* Human monoclonal Ab against RANKL
* Prevent development of osteoclast

33
Q

Denosumab RANKL i admin

A

SC inj every 6mnths
- Fatty tissue of abdomen

+ 1000mg Ca + (=/> 400 IU vit D) daily

34
Q

indication for RANKLi

A
  • Similar or better BMD results than bisphosphonates
  • Best for renal impaired (replete with vit D + Ca)

$$

35
Q

SE for RANKLi

A
  • Musculoskeletal aches
    • Muscle, back, bone , joint pain
  • NVCD
  • Slight tiredness
  • Incr cholesterol levels
  • hypoCa
  • Rarely: osteonecrosis of jaw, atypical femur fractures
  • Do not discontinue: incr risk of spinal column fractures
36
Q

CI for RANKLi

A
  • Eczema
  • Vit D deficiency (replete before inj)
  • HypoCa
  • Preg
  • Do not discontinue suddenly: incr risk of spinal column fractures
37
Q

caution use for RANKLi

A

Use with caution (replete Ca, Vit D) if severe renal impairment
Crcl <10mL/min

38
Q

Estrogens MOA

A

raloxifene (60mg OD)

  • Help maintain BMD (regulator) not directly impact bone
  • Selective oestrogen receptor modulator
    • Mixed oestrogen receptor agonist and antagonist
    • Mimics effect of oestrogen on BMD in postmeno wormen
    • Reduce risk of breast CA
39
Q

estrogen indication

A

1) Early menopause <45yo (prevent osteo)
2) Postmenopausal women (<60yo / 10 yrs of menopausal)

40
Q

SE of estrogen

A
  • Risk of blood clots
    • Stroke
  • Hot flashes
  • Breast/ endometrial cancer
  • VTE
41
Q

calcitonin MOA

A
  • Peptide hormone secreted by parafollicular cells of thyroid gland
  • Reduce blood Ca
    • vs PTH incr blood Ca
  • Inhibit osteoclastic bone resorption
42
Q

calcitonin admin

A

Inj (IV, SC, IM), nasal spray

43
Q

calcitonin SE, CI

A
  • Red streaks on skin
  • Inj site rxn
  • Feeling of warmth
  • Redness of face, neck, arms, upper chest

CI: hypersensitive, hypoCa

44
Q

PTH therapy MOA

A

Teriparatide (20mcg OD)

  • Stimulate new bone fomation
  • Incr bone strength

PTH similar (but more ANABOLIC > anti-resorptive effect)

45
Q

PTH admin

A

SC inj (OD)
- Fatty tissue of abdomen
MAX DURATION 24MNTHS in lifetime (2yrs)
Longer tx incr risk of osteosarcomas (mice)

$$$$

46
Q

PTH SE

A
  • hyperCa
    • Minimal elevation of serum ca
  • Calciphylaxis
  • Worsen stable cutaneous calcification (on skin)
  • Orthostatic hypoTEN
  • Osteosarcoma (mice)
47
Q

PTH CI

A
  • Hx of bone radiation
    • Previous implant or external beam radiation
  • Hypersensitivity
  • Pre-existing hyperCa
  • Skeletal malignancy, bone metastases
    • Metabolic bone diseases
    • Paget’s disease of bone
    • hyperPTH
  • Unexplained elevation of alkaline phosphatases
  • Hereditary disorders predisposing of osteosarcoma
  • Preg
  • Crcl <30mL/min
48
Q

sclerostin inhibitor MOA

A

romosozumab
* Humanised mouse monoclonal Ab against sclerostin
* Removes sclerostin (regulatory factor) of canonical Wnt signaling pathway that regulates bone growth (OSTEOBLAST)
* Incr bone formation and decr bone resorption

49
Q

admin of romosozumab

A

SC inj (once a mnth)
- Fatty tissue of abdomen
USED FOR 12MNTHS (1 yr)

50
Q

romosozumab indication

A
  • Women at hgh risk of fractures
  • Failed/ intolerant to other osteoporosis therapies
    $$$$
51
Q

SE of sclerostin inhibitor

A
  • CVS and stroke events in high risk pts
  • MI
  • Transient hypoCa
  • Hypersensitivity
    • Angioedema, erythema multiforme, urticaria, dermatitis (rash)

Rare:
* Osteonecrosis of jaw
* Atypical femur fractures

52
Q

CI for sclerostin inhibitor

A
  • Hx of CVS events / stroke
    • Within preceding yr
  • Hypersensitivity
  • Uncorrected hypoCa
  • CrCl < 30ml/min
53
Q

adequate Ca intake
hypoCa: < 2.2-2.7 mmol/L

  • Ca requires vit D, low pH and small doses > 1 large dose for better absorption
  • take with food, produce the acid
A

Ca intake: 800-1000 mg/day (18-50yo)
Indication: give suppl if dietary < 700 mg/day (tofu, milk, hard cheese)

DDI:

  • Decr Ca absorption (incr pH): PPI, high fibre diet
  • Decr other drug absorption: Fe, tetracycline, FQ, bisphosphonate, thyroid suppl.
    = Space apart from bisphophonate!!
54
Q

daily vit D intake

A

600IU/d (51-70yo)
800IU/d (>70yo)

55
Q

adequate vit D intake
< 20-30ng/mL

(hyper: > 50-100ng/mL)
* take with food (better absorption)

A

600-800IU/day cholecalciferol

DDI: rifampicin, anticonvulsants (PT, VA, CBP)

cholestyramine, orlistat (binds to fat, vit D is fat soluble) = SPACE OUT

Al containing pdts

56
Q

non pharm

A
  • Exercises (Tai Chi, elastic band, walking)
    • Weight bearing 30mins daily
    • Muscle strengthening, balance 2-3x/ wk
  • Smoking cessation, alcohol, caffeine intake
  • Reduce risks for fall
  • Ca, vit D lvls
57
Q

med review for MEDS that increase fall risk

Pt specific intervention (severity of fragility)
○ Handle bars, suff lighting, cataract, footwear
○ Medication review

A

drowsy, fall risk, ortho hypoTEN, anticholinergic effects:
* BZP, psychotropics, antidep, antihist (1st gen), anarex, codeine

  • cataract, proper footwear, lighting, home modifications

3154 MSK (9 decks)

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