Osteoporosis Flashcards
What is the pathophysiology behind osteoporosis?
Bone loss is faster than bone generation, resulting in weak and brittle bones
Cell types implicated
- Osteoblasts: Responsible for bone matrix synthesis (generate new bone matrix and osteocytes)
and subsequent mineralization
- Osteocytes: initiate formation or resorption responses
- Osteoclasts: Responsible for maintaining mineralised bones, remodelling and mechanosensing
Over time, rate of bone mass decline gets faster - Even worse once women reach menopause
What are some possible causes for decreased bone mass?
- Age
- Menopause – ↓ estrogen results in ↑osteoclast resorption and ↓ osteoblastic bone deposition
- Low serum Ca – causes equilibrium of serum Ca and bone Ca to shift, with Ca moving out of bone
- Alcohol consumption
- Smoking
- Physical inactivity
- Medication use – glucocorticoids, immunosuppressants, antiseizures (esp phenobarbital and phenytoin), aromatase inhibitors, GnRH agonists and antagonists, heparin, chemotherapy
- Secondary to other diseases
What are the clinical manifestations of osteoporosis?
Asymptomatic, often undiagnosed until presented with fragility fracture
- Spine – vertebral compression: height loss, kyphosis (hunchback)
- Hip – neck of femur fracture, IT fracture
- Wrist – Colles fracture
- Humerus
- Pelvis
How should it be decided if patients should go for BMD screening?
Should assess post-menopausal women, men ≥65yo – especially if any risk factors present
OSTA Risk Assessment
- High risk (>20) – consider DXA scan as the chance of finding osteoporosis is high in this group
- Medium risk (0-20) – consider DXA scan if any other risk factors for osteoporosis is present
- Low risk (0) – consider deferring DXA
- OSTA Score=0.2 ×[Body weight (kg)-Age (years)]
Female: Low: > -1, Intermediate: -1 to -4, High: < -4 Male: Low: > -1, Intermediate: -1 to -6, High: < -6
How is osteoporosis diagnosed?
Hx of fragility fracture
- Occurs spontaneously or from minor trauma that would not ordinarily result in a fracture
- Asymptomatic vertebral fracture can be identified as a >20% decrease in vertebral height
Bone mineral density (BMD) measurement using DXA hip and/or spine
- Dual-energy X-ray absorptiometry
- T-score
- Z-score
Clinical Hx, physical exam and labs also done to exclude secondary causes of bone loss (esp if Z-score ≤ -2 SD)
- SCr – check for CKD-MBD
- CBC – check malignancy & malabsorption
- 25-OH Vit D – check baseline (>20ng/mL optimal)
- Corrected Ca (elevated may suggest hyperparathyroidism, decreased may suggest malabsorption, vitamin D deficiency)
How is T-score for osteoporosis interpreted?
Compares BMD against a young adult reference population
→ ≤ -2.5 SD → osteoporosis
→ -1 to -2.5 SD → osteopenia
→ ≥ -1 SD → normal bone density
How is Z-score for osteoporosis interpreted?
Compares BMD against expected BMD for the patient’s age and sex
→ ≤ -2 SD suggests coexisting problems (e.g. glucocorticoid therapy or alcoholism) that can contribute to osteoporosis
When should osteoporosis treatment start?
- Patients presenting with fragility fracture or
- Patients without fragility fracture but DXA BMD T-score ≤ -2.5 or
- Patients without fragility fractures but osteopenic DXA BMD T-score (-1 to -2.5) and high fracture risk (FRAX)
What is the MOA of the bisphosphonates?
Slow bone loss by increasing osteoclast cell death
How are bisphosphonates used in osteoporosis therapy?
Tx duration for low fracture risk
- PO: 5 years
- IV: 3 years
Tx duration for low fracture risk
- PO: 10 years
- IV: 6 years
Check BMD Q2-3 years – if satisfactory, can consider drug holiday (ie stop bisphosphonate)
If drug holiday, check BMD again in another 2-3 years and see if to restart Tx
How should PO bisphosphonates be taken?
PO Admin Instructions (prevent GI irritation): Take on an empty stomach first thing in the morning. Take tablet with ≥240ml of plain water (approx. 1 mug). Wait ≥30 min before consuming anything.
→ Normal tab – Do not chew or crush
→ Effervescent tab – Dissolve in the water and wait for fizzing to stop (can stir to speed up dissolution). Drink the solution, then drink extra plain water after than (≥30ml). Do not swallow the undissolved tablet whole, chew the tablet or leave the tablet to dissolve in mouth
What are the side effects of the bisphosphonates?
→ Significant: atypical femoral fractures (w prolonged use), severe bon/joint/muscle pain, upper GI irritation, ocular effects, hypocalcaemia, osteonecrosis of jaw and external auditory canal
→ PO: nausea, abdominal pain, heartburn-like symptoms (check admin technique)
→ IV: flu-like symptoms
What are the contraindications for bisphosphonates?
Hypocalcaemia, abnormalities of the oesophagus which may delay emptying, severe renal impairment (CrCl < 30ml/min), pregnancy and lactation
Precautions: active upper GI disease, risk factors for osteonecrosis of jaw or external auditory canal
What is the MOA of denosumab?
Human monoclonal antibody against RANKL – prevents development of osteoclasts
How is denosumab dosed?
SC injection Q6/12 – Co-administer 1000mg Ca + ≥400 IU vitamin D daily
DO NOT discontinue – may increase risk of spinal column fractures
