Disorders Of Bone Health (otesoporosis) Flashcards
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
Osteoporosis risk factors
Prevalence in the UK – osteoporosis affects
~ 2% of women at the age of 50y
~ almost 50% of women at 80 y
It is considered a “silent disease” as it is asymptomatic unless a fracture has occurred. Consider assessing high risk individuals.
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
-oestoclasts
-osteocytes
osteoblasts
bone forming cells
Osteoclasts
responsible for bone breakdown/resorption
increasing age, there is increased osteocalst activity
Osteocytes
mature bone cells within the bone matrix, help to maintain bone and act as mechanosensors
Regulating Factors- peak bone mass (5)
Genetics (70-80 %)
Body Weight
Sex hormones
Diet
Exercise
Regulating factors- bone loss (7)
Sex hormone deficiency
Body weight
Genetics
Diet
Immobility
Diseases ( eg rheumatoid arthritis)
Drugs especially glucocorticoids, aromatase inhibitors
Osteoporosis- clinical outcomes (3)
Osteoporotic fractures: major cause of pain, disability, death.
~50% of hip fracture patients cannot live independently.
~20% of hip fracture patients die within a year of their fracture.
Osteoporosis- common fracture sites (4)
Neck of femur
Vertebral body
Distal radius
Humeral neck
Osteoporosis- Who to assess? (4)
Anyone >age 50 years with risk factors
Anyone under 50 years with very strong clinical risk factors eg
~Early menopause
~Glucocorticoids
Osteoporosis- when to refer to DXA scan?
Anyone with a 10 year risk assessment for any OP fracture of at least 10%
Clinical Risk Factors for Fragility Fracture- non modifiable (7)
Age
Gender
Ethnicity
Previous fracture
Family history
Menopause ≤ 45 years
Co-existing diseases
Clinical Risk Factors for Fragility Fracture- modifiable (6)
BMD
Alcohol
Weight
Smoking
Physical inactivity
Pharmacological risk factors
Fracture Risk Calculators (3)
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
Fracture Risk Calculators (3)
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
Osteoporosis- who to refer to DEXA scan (4)
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 use risk assessment tool FRAX or Qfracture > 10% risk fracture over 10 years
Bone density measurements (5)
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
Bone density measurements (5)
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
Assessment osteoporosis
History and examination
U+Es LFTs Bone biochemistry
FBC PV TSH
Consider:
Protein electrophoresis/Bence Jones proteins
Coeliac antibodies
Testosterone
25OH Vitamin D PTH
Lifestyle advice for management of osteoporosis (5)
High intensity strength training
Low-impact weight-bearing exercise (standing, one foot always on the floor)
Avoidance of excess alcohol
Avoidance of smoking
Fall prevention
Diet- management osteoporosis (6)
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
Drugs- management osteoporosis (7)
Calcium & vitamin D supplementation
Bisphosphonates
Denosumab
Teriparatide
Romosozumab
HRT
Testosterone
Calcium and Vitamin D (6)
reduce risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake or limited sunlight exposure.
If low exposure to sun or house-bound:
-consider at risk of Vitamin D deficiency
Calcium supplements should not be taken within 2 hours of oral bisphosphonates
If dietary calcium is adequate, >700 mg daily
Vitamin D only may be preferred as the osteoporosis treatment adjunct
Biphosphonates - what are they? (3)
analogues of pyrophosphate that adsorb onto bone within the matrix
ingested by osteoclasts leading to cell death thereby inhibiting bone resorption
Anti-resorptive agents – alendronate and risedronate
Biphosphonates- how do they help? (4)
increases BMD by 5-8%
Prevent bone loss at all sites vulnerable to osteoporosis
Reduce risk of hip and spine fracture
reduce the risk of fragility fracture by ~50% in patients with post-menopausal osteoporosis
Bisphosphonates- duration? (3)
Good data for benefit for 5 years (10 y if vertebral fracture)
Long-term concerns re: osteonecrosis of the jaw, atypical fractures
Consider “bone holiday” – though no robust evidence base
Bone remodelling (5)
Bone undergoes a cycle of remodelling in a programmed sequence at discrete foci called bone remodelling units
1.osteoclasts appear on a previously inactive surface and begin to resorb the bone
2.Osteoclasts are then replaced by osteoblasts that fill the cavity by putting down osteoid that is mineralised to form new bone
3.After a normal bone remodelling cycle the resorption cavity is completely refilled with new bone
4.However, in osteoporosis, there is a relative or absolute increase in resorption over formation that leads to increased bone loss
__________
Zoledronic Acid (4)
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- mech action (2)
fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL (receptor activator of nuclear factor-kB ligand)
prevents activation of its receptor, RANK, inhibiting development and activity of osteoclasts, decreasing bone resorption and increasing bone density.
Denosumab- dose + side effects (4)
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
When to treat osteoporosis (2)
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
Paget’s disease of bone- aetiology + risk factors (4)
may be a viral/environmental/biomechanical trigger in genetically predisposed individual
Rare < 40 y; incidence increases with age:
> 55y: 3% of UK population
>85y: ~ 10%
Paget’s disease of bone - bones it affects (4)
long bones
pelvis
lumbar spine
skull predominantly
Paget’s disease of bone - presentation (7)
Presents with=
-bone pain
-deformity
-deafness
-compression neuropathies
Osteosarcoma is a rare complication
incidental finding on
- X-ray (XR)
-isolated high alkaline phosphatase
Paget’s disease of bone- diagnosis (3)
Diagnose on XR;
-isotope bone scan shows the distribution of disease
-biochemistry shows raised alkaline phosphatase with otherwise normal LFTs
Paget’s disease of bone
- treatment
Treat with bisphosphonates if pain not responding to analgesia
Osteogenesis Imperfecta (3)
Rare group of genetic disorders mainly affecting bone
Most are secondary to mutations of type 1 collagen genes (COL1A1, COL1A2)
Most are autosomal dominant inheritance
At least 8 types, of varying severity
Type 1: mild
Type 2: neonatal (lethal)
Types 3 and 4: very severe
Osteogenesis Imperfecta- presentation (5)
May be associated=
-blue sclerae
-dentinogenesis imperfecta
more severe forms present with fractures in childhood
mild form may not present until adulthood
Important differential diagnosis for suspected non-accidental injury
Osteogenesis Imperfecta- treatment (4)
There is no cure only =
-fracture fixation
-surgery to correct deformities
-bisphosphonates
