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
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
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)
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)
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 )
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)
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
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
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
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
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
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
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)
- Often undx until presented with fragility fracture
- # give rise to: pain & disability
- Incr healthcare cost, nursing home placement, mortality incr (HAI)
- Indirect cost: hire helpers, caregiver taking leave
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)
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
16
Q
goals of tx
A
1) Prevent fractures — BMD as a marker (reduction in potential # risk)
2) Improve QOL
3) Reduce economic burden
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)
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
19
Q
Bisphosphonates MOA
Risedronate, Alendronate
A
Slow bone loss by incr osteoclast cell death
bone growth > resorption
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
21
Q
alendronate dose
A
70mg once per week (same day)
22
Q
bispho IV admin
A
Zoledronic acid (IV: 5mg 30min infusion per yr)
Once a yr (15-30mins via cannula vein)
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
ONJ risk factors
□ Comor (anemia, cancer, coag, preexist dental infection)
□ DDI (chemo, CS, denosumab, angiogenesis, bisphos)
□ Invasive dental procedure
□ Hx cancer, radiography
□ Poor oral hygiene
26
ONJ counsel
□ 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
atypical femoral # risk
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
CI for bispho
* HypoCa
* Abnormalities in oesophagus (delay emptying)
* Reflux oesophagitis
* Preg, lactation
IV: Vit D def -- replete before infusion
29
caution in bispho
- 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
monitor for bispho
* 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
duration of bispho
* 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
RANK ligand inhibitors MOA
Denosmab
* Human monoclonal Ab against RANKL
* Prevent development of osteoclast
33
Denosumab RANKL i admin
SC inj every 6mnths
- Fatty tissue of abdomen
+ 1000mg Ca + (=/> 400 IU vit D) daily
34
indication for RANKLi
* Similar or better BMD results than bisphosphonates
* Best for renal impaired (replete with vit D + Ca)
$$
35
SE for RANKLi
* Musculoskeletal aches
* Muscle, back, bone , joint pain
* NVCD
* Slight tiredness
* Incr cholesterol levels
* hypoCa
* Rarely: osteonecrosis of jaw, atypical femur fractures
* Do not discontinue: incr risk of spinal column fractures
36
CI for RANKLi
* Eczema
* Vit D deficiency (replete before inj)
* HypoCa
* Preg
* Do not discontinue suddenly: incr risk of spinal column fractures
37
caution use for RANKLi
Use with caution (replete Ca, Vit D) if severe renal impairment
Crcl <10mL/min
38
Estrogens MOA
raloxifene (60mg OD)
* Help maintain BMD (regulator) not directly impact bone
* Selective oestrogen receptor modulator
* Mixed oestrogen receptor agonist and antagonist
* Mimics effect of oestrogen on BMD in postmeno wormen
* Reduce risk of breast CA
39
estrogen indication
1) Early menopause <45yo (prevent osteo)
2) Postmenopausal women (<60yo / 10 yrs of menopausal)
40
SE of estrogen
* Risk of blood clots
* Stroke
* Hot flashes
* Breast/ endometrial cancer
* VTE
41
calcitonin MOA
* Peptide hormone secreted by parafollicular cells of thyroid gland
* Reduce blood Ca
* vs PTH incr blood Ca
* Inhibit osteoclastic bone resorption
42
calcitonin admin
Inj (IV, SC, IM), nasal spray
43
calcitonin SE, CI
* Red streaks on skin
* Inj site rxn
* Feeling of warmth
* Redness of face, neck, arms, upper chest
CI: hypersensitive, hypoCa
44
PTH therapy MOA
Teriparatide (20mcg OD)
* Stimulate new bone fomation
* Incr bone strength
PTH similar (but more ANABOLIC > anti-resorptive effect)
45
PTH admin
SC inj (OD)
- Fatty tissue of abdomen
MAX DURATION 24MNTHS in lifetime (2yrs)
Longer tx incr risk of osteosarcomas (mice)
$$$$
46
PTH SE
* hyperCa
* Minimal elevation of serum ca
* Calciphylaxis
* Worsen stable cutaneous calcification (on skin)
* Orthostatic hypoTEN
* Osteosarcoma (mice)
47
PTH CI
* Hx of bone radiation
* Previous implant or external beam radiation
* Hypersensitivity
* Pre-existing hyperCa
* Skeletal malignancy, bone metastases
* Metabolic bone diseases
* Paget's disease of bone
* hyperPTH
* Unexplained elevation of alkaline phosphatases
* Hereditary disorders predisposing of osteosarcoma
* Preg
* Crcl <30mL/min
48
sclerostin inhibitor MOA
romosozumab
* Humanised mouse monoclonal Ab against sclerostin
* Removes sclerostin (regulatory factor) of canonical Wnt signaling pathway that regulates bone growth (OSTEOBLAST)
* Incr bone formation and decr bone resorption
49
admin of romosozumab
SC inj (once a mnth)
- Fatty tissue of abdomen
USED FOR 12MNTHS (1 yr)
50
romosozumab indication
* Women at hgh risk of fractures
* Failed/ intolerant to other osteoporosis therapies
$$$$
51
SE of sclerostin inhibitor
* 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
CI for sclerostin inhibitor
* Hx of CVS events / stroke
* Within preceding yr
* Hypersensitivity
* Uncorrected hypoCa
* CrCl < 30ml/min
53
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
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
daily vit D intake
600IU/d (51-70yo)
800IU/d (>70yo)
55
adequate vit D intake
< 20-30ng/mL
(hyper: > 50-100ng/mL)
* take with food (better absorption)
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
non pharm
* 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
med review for MEDS that increase fall risk
Pt specific intervention (severity of fragility)
○ Handle bars, suff lighting, cataract, footwear
○ Medication review
drowsy, fall risk, ortho hypoTEN, anticholinergic effects:
* BZP, psychotropics, antidep, antihist (1st gen), anarex, codeine
* cataract, proper footwear, lighting, home modifications
3154 MSK
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