Disorders of Bone Health Including Osteoporosis Flashcards
What is Osteoporosis?
Progressive systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
Bone physiology?
Bone undergoes a continual remodelling cycle at distinct sites called bone remodelling units. This contributes to calcium homeostasis and also to skeletal repair.
~10% of the adult skeleton is remodelled each year
Three cell types contribute to bone homeostasis
- osteoblasts are bone forming cells
- osteoclasts are responsible for bone breakdown/resorption
- osteocytes are mature bone cells within the bone matrix, help to maintain bone and act as mechanosensors
With increasing age, there is increased osteocalst activity which is not matched by increased osteoblast activity. This imbalance of bone breakdown and formation leads to osteoporosis.
Bone Microarchitecture Influences Bone Strength. how does this associate with age?
What are the factors for Peak bone mass vs Bone loss?
Peak Bone Mass:
Genetics (70-80 %)
Body Weight
Sex hormones
Diet
Exercise
Bone Loss:
Sex hormone deficiency
Body weight
Genetics
Diet
Immobility
Diseases ( eg rheumatoid arthritis)
Drugs especially glucocorticoids, aromatase inhibitors
Who is at risk and who to treat?
Target therapeutic intervention
at those at high risk of low impact fracture. Assess fracture risk.
How to use risk factor assessment?
Who to assess?
- Anyone >age 50 years with risk factors
- Anyone under 50 years with very strong clinical risk factors eg
-Early menopause
-Glucocorticoids
When to refer for DXA?
* Anyone with a 10 year risk assessment for any OP fracture of at least 10%
Clinical Risk Factors for Fragility Fracture?
Non-modifiable
Age
Gender
Ethnicity
Previous fracture
Family history
Menopause ≤ 45 years
co-existing disease
Modifiable:
BMD
Alcohol
Weight
Smoking
Physical inactivity
Pharmacological risk factors
SIGN Guideline 142?
Guideline based around fracture risk and not bone mineral density
- Address risk factors for fracture
Non-modifiable
Modifiable - Assessment of fracture risk
Which tool to use
Fracture Risk Calculators?
- Allow calculation of absolute risk by incorporating additional risk factors rather than just BMD.
- Prediction of 10 year fracture risk of major osteoporotic fracture or hip fracture
- Some limitations
Who to refer for DEXA?
Patients over 50 y with low trauma fracture – often identified through Fracture Liaison Service (FLS) – “Stop at One”
Patients at increased risk of fracture based on risk factors – calculated using risk assessment tool eg FRAX or Qfracture. > 10% risk of fracture over 10 years
Assessing Bone Density
BMD predicts fracture risk independently of other risk factors
DXA scans (Dual Energy Xray Absorptiometry) are most widely used method of measuring BMD
Normal : BMD within 1 SD of the young adult reference mean
Osteopenia (low bone mass) :BMD >1 SD below the young adult mean but <2.5 SD below this value
Osteoporosis : BMD ≥ 2.5 SD below the young adult mean
Severe osteoporosis : BMD ≥2.5 SD below the young adult mean with fragility fracture
If younger than 20 y, only Z score reported
The lower the BMD the higher bone fx
T
Drug treatments?
Calcium & vitamin D supplementation
Bisphosphonates
Denosumab
Teriparatide
Romosozumab
HRT
Testosterone
Diet Mx?
Have high calcium diet
RNI 700mg calcium (2-3 portions from milk and dairy foods group)
Postmenopausal women aim dietary intake 1000 mg calcium per day to reduce fracture risk (3-4 portion calcium rich foods)
Non-dairy sources include
bread and cereals (fortified)
fish with bones, nuts,
green vegetables, beans
Bisphosphonates therapy?
analogues of pyrophosphate that adsorb onto bone within the matrix
ingested by osteoclasts leading to cell death thereby inhibiting bone resorption
filling of resorption sites by new bone increases BMD by 5-8%
Anti-resorptive agents – alendronate and risedronate
for 5 years (10 years for vertebral fx)
Long term- consider “bone holday” for it
Prevent bone loss at all sites vulnerable to osteoporosis
Reduce risk of hip and spine fracture
Zoledronic Acid?
Once yearly IV infusion for 3 years
1 in 3 acute phase reaction with first infusion – paracetamol
~ 70% reduction in vertebral fracture, 40% reduction in hip fracture
Consider if intolerant of oral bisphosphonates or unable to comply with dosing regime
Denosumab
Denosumab – fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL (receptor activator of nuclear factor-kB ligand)
This prevents activation of its receptor, RANK, inhibiting development and activity of osteoclasts, decreasing bone resorption and increasing bone density.
Subcutaneous injection 6 monthly
Compared to placebo, reduces risk of vertebral fracture by ~68%, hip fracture by 40% and non-vertebral fracture by ~20%.
Adverse effects: Hypocalcaemia, eczema, cellulitis
No contraindication in severe renal impairment
Denosumab
Denosumab – fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL (receptor activator of nuclear factor-kB ligand)
This prevents activation of its receptor, RANK, inhibiting development and activity of osteoclasts, decreasing bone resorption and increasing bone density.
Subcutaneous injection 6 monthly
Compared to placebo, reduces risk of vertebral fracture by ~68%, hip fracture by 40% and non-vertebral fracture by ~20%.
Adverse effects: Hypocalcaemia, eczema, cellulitis
No contraindication in severe renal impairment
Teriparatide
Recombinant parathyroid hormone (1-34)
Stimulates bone growth rather than reducing bone loss – anabolic agent
Consider if severe osteoporosis - particularly if high risk of vertebral fracture
Romosozumab
Wnt signaling pathway plays a role in skeletal homeostais and bone remodelling. Sclerostin is an inhibitor of this pathway
Romosozumab is a humanised monoclonal antibody that binds to sclerostin, preventing it from having this inhibitory effect
Acts as an anabolic agent, increasing bone mineral density, also reduces bone resorption
Given as a monthly injection for 12 months
Contraindication - previous MI/CVA
When to treat?
Majority of patients, consider treatment with antiresorptive therapy when T score </= - 2.5
If ongoing steroid requirement >/=7.5mg prednisolone for 3 months or more or if there is a prevalent vertebral fracture, consider treatment with T score < -1.5 as fracture risk increased
what is the impact of steroid (corticosteroids) on bones?
Direct: Reduction of osteoblast activity and lifespan
Suppression of replication of osteoblast precursors
Reduction in calcium absorption
Indirect: Inhibition of gonadal and adrenal steroid production
Paget’s disease of bone?
Uncertain aetiology: may be a viral/environmental/biomechanical trigger in genetically predisposed individual
Affects long bones, pelvis, lumbar spine and skull predominantly
Rare < 40 y; incidence increases with age
Presents with bone pain, deformity, deafness, compression neuropathies
Osteosarcoma is a rare complication
May be incidental finding on X-ray (XR) or isolated high alkaline phosphatase
Diagnose on XR; isotope bone scan shows the distribution of disease; biochemistry shows raised alkaline phosphatase with otherwise normal LFTs
Treat with bisphosphonates if pain not responding to analgesia
Abnormal osteoclastic activity followed by increased osteoblastic activity
Abnormal bone structure with reduced strength and increased fracture risk
May be single site (monostotic) or multiple sites (polyostotic)
