osteo Flashcards
osteoporosis definition
- 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
pathophysiology of osteoporosis
- 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
cells involved in osteo
- osteoclast (break down) – activated by RANKL
- osteoblast (growth) – sclerostin inhibits growth factor
- osteocyte (release RANKL and sclerostin <– PTH affects)
osteoporosis risk factors
- 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)
glucocorticoids cause 2nd osteoporosis
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 )
med assoc w/ osteoporosis
○ Prolonged systemic CS
○ Abx: FQ
○ Antiseizure: CBP, PB, PT
○ PPI
○ GnRH agonist/ antagonist
○ heparin
○ chemo immunosuppressant
○ breast cancer therapies (decr estrogen)
secondary causes of osteoporosis
- 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
osteo self assessment tool OSTA (post menopausal women)
(need for BMD screen)
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
BMD testing
- 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
BMD score
Z vs T
- 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
3 T-scores
T score ≤ -2.5 SD = osteoporosis
T score -1 to -2.5 SD = osteopenia
T score ≥ -1 SD = normal BD
Fracture risk assessment tool (FRAX)
- 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
osteoporosis presentation
- 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
When to start tx
- 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)
osteo tx plan
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
goals of tx
1) Prevent fractures — BMD as a marker (reduction in potential # risk)
2) Improve QOL
3) Reduce economic burden
factors to consider when decide to tx
- fracture risk (high)
- past fracture
- BMD ( T score < -2.5)
- age (>65yo)
- risk for falls/ bone loss (FRAX)
vit D and bone metabolism
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
Bisphosphonates MOA
Risedronate, Alendronate
Slow bone loss by incr osteoclast cell death
bone growth > resorption
bispho ADMIN PO
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
alendronate dose
70mg once per week (same day)
bispho IV admin
Zoledronic acid (IV: 5mg 30min infusion per yr)
Once a yr (15-30mins via cannula vein)
bispho tx indication and duration
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
bispho SE
- 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)
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
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
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 #)
CI for bispho
- HypoCa
- Abnormalities in oesophagus (delay emptying)
- Reflux oesophagitis
- Preg, lactation
IV: Vit D def – replete before infusion
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
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
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)
RANK ligand inhibitors MOA
Denosmab
* Human monoclonal Ab against RANKL
* Prevent development of osteoclast
Denosumab RANKL i admin
SC inj every 6mnths
- Fatty tissue of abdomen
+ 1000mg Ca + (=/> 400 IU vit D) daily
indication for RANKLi
- Similar or better BMD results than bisphosphonates
- Best for renal impaired (replete with vit D + Ca)
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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
CI for RANKLi
- Eczema
- Vit D deficiency (replete before inj)
- HypoCa
- Preg
- Do not discontinue suddenly: incr risk of spinal column fractures
caution use for RANKLi
Use with caution (replete Ca, Vit D) if severe renal impairment
Crcl <10mL/min
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
estrogen indication
1) Early menopause <45yo (prevent osteo)
2) Postmenopausal women (<60yo / 10 yrs of menopausal)
SE of estrogen
- Risk of blood clots
- Stroke
- Hot flashes
- Breast/ endometrial cancer
- VTE
calcitonin MOA
- Peptide hormone secreted by parafollicular cells of thyroid gland
- Reduce blood Ca
- vs PTH incr blood Ca
- Inhibit osteoclastic bone resorption
calcitonin admin
Inj (IV, SC, IM), nasal spray
calcitonin SE, CI
- Red streaks on skin
- Inj site rxn
- Feeling of warmth
- Redness of face, neck, arms, upper chest
CI: hypersensitive, hypoCa
PTH therapy MOA
Teriparatide (20mcg OD)
- Stimulate new bone fomation
- Incr bone strength
PTH similar (but more ANABOLIC > anti-resorptive effect)
PTH admin
SC inj (OD)
- Fatty tissue of abdomen
MAX DURATION 24MNTHS in lifetime (2yrs)
Longer tx incr risk of osteosarcomas (mice)
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PTH SE
- hyperCa
- Minimal elevation of serum ca
- Calciphylaxis
- Worsen stable cutaneous calcification (on skin)
- Orthostatic hypoTEN
- Osteosarcoma (mice)
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
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
admin of romosozumab
SC inj (once a mnth)
- Fatty tissue of abdomen
USED FOR 12MNTHS (1 yr)
romosozumab indication
- Women at hgh risk of fractures
- Failed/ intolerant to other osteoporosis therapies
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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
CI for sclerostin inhibitor
- Hx of CVS events / stroke
- Within preceding yr
- Hypersensitivity
- Uncorrected hypoCa
- CrCl < 30ml/min
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!!
daily vit D intake
600IU/d (51-70yo)
800IU/d (>70yo)
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
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
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
