characteristics of osteoporosis
1) low bone density
2) microarchitecture disruption (impaired mineralisation)
3) decreased bone strength
4) increased risk of fractures
processes contributing to decrease bone mass
1) Decreased bone formation
2) Excessive bone resorption
causes of decreased bone mass
1) age
2) menopause
3) low serum Ca
- increased oxidative stress -> increased osteoblast apoptosis
4) alcohol consumption, smoking
- increased RANKL activation -> increased osteoclast growth -> increased bone resorption
5) secondary causes
- glucocorticoid use induced osteoporosis
** inhibit decrease in osteoblast differentiation and increase death of osteoblast and osteocytes
clinical presentation of osteoporosis
- asymptomatic, no pain until fracture actually happen
- often undiagnosed until pt present w low-trauma fragility fracture
-spine: height loss due to compression, kyphosis (forward rounding of upper back)
what to look out for osteoporosis
1) family history of osteoporosis or fragility fractures
2) previous fragility fracture
3) low body weight
4) advanced age
5) height loss (Decrease by > 2cm over the past few years)
6) early menopause (<45yo)
7) presence of diseases that can lower bone density
8) diet (low Ca intake < 500mg/day)
9) excessive alcohol intake (>2 units/day)
10) smoker
11) prolonged immobility
12) history of falls
diagnosis components for osteoporosis
1) history of fragility fracture
2) bone mineral density (BMD) measurement
history of fragility fracture for osteoporosis
- vertebral, hip, wrist, humerus, rib, pelvis
- occur spontaneously or from minor trauma that would not normally result in fracture
BMD measurement for osteoporosis
1) indication
- post menopausal women
** classifications using OSTA tool
–> high risk (>20): do DXA scan
–> medium risk (0-20): do DXA scan if presence of other risk factors - men > 65 yo
2) how to do BMD measurement?
- DXA hip and/or spine
3) T-score
- ≤ -2.5 SD: osteoporosis
- -1 to -2.5 SD: osteopenia (do FRAX)
- ≥ -1 SD: normal bone density
4) Z-score
- ≤ -2 SD indicates coexisting problems that contribute to osteoporosis
indication for treatment initiation for osteoporosis
1) fragility fracture
2) no fragility fracture but DXA T-score ≤ -2.5 SD
3) no fragility fracture and osteopaenic but high risk fracture cuz FRAX scoring indicates 10-yr probability for major osteoporotic fracture ≥ 20% or hip fracture ≥ 3%
what to do when initiating treatment for osteoporosis
check serum Ca and 25(OH) Vit D levels
- serum 25(OH) Vit D should be 20-50 mg/dL
- correct serum Ca levels before initiating therapy with Ca and Vit D supplement
treatment algorithm for osteoporosis
1st line: PO bisphosphonates
2nd line: IV bisphosphonates, denosumab
alternative therapies: antiresorptive agents (oestrogen, calcitonin), anabolic agents (romosozumab, parathyroid hormone therapies)
types of bisphosphonates
1) PO (cheapest)
- risedronate 35mg q weekly
- alendronate 50mg q weekly
2) IV
- zoledronic acid 5mg q year as 30 mins IV infusion
- ensure adequate hydration prior to administration
bisphosphonates PO dosing administration
- take oral on empty stomach w at least 240mL plain water and wait 30 mins before taking food cuz F severely affected by food and drinks
- avoid lying down for 30 mins after taking drug to prevent acid reflux
- X take with Ca, Al, Mg, Fe containing products within 2 hrs of meds
MOA of bisphosphonates
slow bone loss by increasing osteoclast cell death
bisphosphonates AE - significant
1) atypical femoral fractures after prolonged use
- discontinue therapy
2) severe bone/joint/muscle pain, upper GI mucosa irritation, ocular effects (iritis, uveitis), hypocalcemia
3) osteonecrosis of jaw (ONJ)
- risk factors
** invasive dental procedures while on bisphosphonates
** history of cancer/radiotherapy
** poor oral hygiene - counselling points
** smoking cessation
** avoid invasive dental procedures
** good oral hygiene - discontinue therapy based on risk/benefit and consult dentist
4) osteonecrosis of external auditory canal
bisphosphonates AE - PO related
N, abdominal pain, heart-burn like symptoms
bisphosphonates AE - IV related
flu-like symptoms
bisphosphonates CI
1) hypocalcemia
2) abnormalities of esophagus which may delay emptying
3) severe renal impairment (CrCl < 30)
4) pregnancy, lactation
5) for PO: inability to stand/sit up for ≥ 30 mins (bedbound, dementia)
bisphosphonates precautions
1) Active upper GI disease
2) risk factors for developing ONJ or osteonecrosis of external auditory canal
bisphosphonates treatment duration
1) low fracture risk
- PO 5 yrs
- IV 3 yrs
- restart treatment after 2 yrs if BMD decrease by > 4-5% or treatment criteria met
2) high risk fracturs
- requirements: 10 yr total risk of fractures > 20%, previous vertebra fracture
- PO 10 years
- IV 6 years
denosumab MOA
- human mab against RANKL
- prevent development of osteoclast
denosumab efficacy vs bisphosphonates
similar or better bone density results
dosing instructions for denosumab
- subcu injection every 6 monthly
- co-administer 1000mg Ca + ≥ 400 IU Vit D daily
denosumab AE
- muscle, back, bone, joint pain
- N/V/C/D, slight tiredness, increased cholesterol level
- ONJ or atypical femur fracture
- X discontinue cuz increased risk of spinal column fracture (counsel so pt won’t default appointment)
