Bone Health and Osteoporosis Flashcards
Definition of osteoporosis?
Progressive systemic skeletal disease characterised by low bone mass and micro-architectural bone tissue deterioration
There is a consequent increase in bone fragility and fracture susceptibility
Common fracture sites in the skeleton?
- Neck of femur (incidence rises dramatically when >70)
- Vertebral body
- Distal radius (most frequent up to the age of 70)
- Humeral neck
Morbidity and mortality assoc. with hip fractures?
1/2 of patients lose independence
1/5 die within a year of their fracture
Occurrence of osteoporotic fractures in women?
Majority of hip fractures occur in women >75 years
Reason for women suffering more osteoporotic fractures?
Women have lower peak bone mass
AND
Accelerated loss of bone during the menopause
AND
Increased longevity
Presentation of vertebral fractures?
Many present “silently” (with no symptoms)
Describe the domino fracture effect
A vertebral fracture increases the risk of kyphosis
Also, if a patient has had 1 fracture, they have an increased risk of another fracture
Describe the domino fracture effect
A vertebral fracture increases the risk of kyphosis
Also, if a patient has had 1 fracture, they have an increased risk of another fracture
Where does remodelling of bone occur?
Bone undergoes a continual remodelling cycle at distinct sites (BONE REMODELLING UNITS)
Purpose of bone remodelling?
10% of the adult skeleton is remodelled every year, which contributes to:
• Calcium homeostasis
• Skeletal repair
Process of bone remodelling?
Beginning of cycle:
• Osteoclasts appear on a previously inactive surface and begin to resorb bone
They are then replaced with osteoblasts that fill the cavity, by laying down OSTEOID; this is MINERALISED, to form new bone
Main problem with bone remodelling in osteoporosis?
There is a relative or absolute increase in resorption over formation; this leads to increased bone loss
Structure when osteoporotic bone loss occurs?
Osteoporotic bone has:
• Loss of bone
• Large spaces
• Breaks in the microscopic architecture (overall weakened bone that fractures easily)
Regulation factors of peak bone mass?
- Genetics (most important factor)
- Body weight (part. being underweight)
- Sex hormones (oestrogen; post-menopause acceleration of bone loss)
- Diet
- Exercise
Regulating factors of bone loss?
- Sex hormone deficiency
- Body weight
- Genetics
- Diet
- Immobility
- Diseases
- Drugs, e.g: steroids, aromatase inhibitors
Age at which peak bone mass is reached?
Bone mass increases in men and women until a peak is attained, at ~30 years
This is the consolidated and maintained until the patient reaches 40
Age at which bone mass starts to decrease?
In both sexes, slow rate of bone loss starts at 40 years; but, in post-menopausal women, there is accelerated bone loss
Which patients with are targeted with therapeutic intervention?
At those with high risk of low impact fracture
Non-modifiable clinical risk factors for fragility fracture?
Age, gender and ethnicity
Previous fracture
FH
Early menopause (≤ 45 years)
Modifiable clinical risk factors for fragility fracture?
BMD (bone mineral density)
Alcohol and smoking
Weight
Physical inactivity
Other clinical risk factors for fragility fracture?
Co-morbidities
Pharmacological risk factors
Use of the WHO fracture risk calculator (FRAX)?
Allows calculation of absolute risk, by incorporating additional risk factors (rather than just BMD)
It produces a prediction of the 10 year risk of major osteoporotic fracture or hip fracture
Advantages of FRAX?
Freely available (internet)
Calculates 10 year absolute risk of hip or major osteoporotic fracture
Can be used with or without BMD
Questions asked in FRAX)
- Age
- Gender
- BMI
- Previous fracture
- Smoking
- Alcohol ≥3 u/d
- Steroids
- RA, diabetes, OI, untreated hyperthyroidism, hypogonadism, premature menopause, malnutrition, malabsorption, chronic liver disease
Disadvantages of FRAX?
Underestimates vertebral fracture risk
Same level of risk assigned to all secondary causes
Dichotomised variables smoking/alcohol
Advantages of Qfracture?
Freely available (internet)
More variables included, e.g: dementia, PD, medications
Hx of falls or resident in nursing homes
Smoking and alcohol can be given in quantities
Can use variable time for absolute risk
Advantages of Qfracture?
Does not inc. BMD, when available
Who should have risk factor assessment?
Anyone >age 50 with risk factors
Anyone <50 years with very strong clinical risk factors:
• Early menopause
• Glucocorticoids
When should a patient be referred for a DEXA scan?
Any patient with a 10 year risk assessment of at least 10%, for any osteoporotic fracture
How is bone density assessed?
Bone mineral density predicts fracture risk INDEPENDENT of any other risk factors
DEXA scan are usually used to measure BMD
Interpreting DEXA scan results?
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 the patient is <20 years old, how is the DEXA scan result reported?
Only the Z score is reported
Relationship between BMD and fracture risk?
As BMD decreases, verterbal fracture risk increases
Ix for osteoporosis?
U&Es, LFTs, FBC, PV and TSH
Bone biochemistry
Consider doing: • Protein electrophoresis • Urinary Bence Jones proteins (indicate multiple myeloma, a bone marrow malignancy, which can cause osteoporosis) • Coeliac antibodies • Testosterone • 24-OH vitamin D • PTH
Secondary causes of osteoporosis?
Endocrine:
• Hyperthyroidism
• Hyperparathyroidism
• Cushing’s disease
GI: • Coeliac disease • IBD • Chronic liver disease • Chronic pancreatitis
Respiratory:
• CF
• COPD
Renal:
• Chronic kidney disease
Lifestyle advice for Mx of osteoporosis?
High intensity strength-training and low-impact weight bearing exercise (standing with one foot always on the floor)
Avoid smoking and excess alcohol
Prevent falling
Calcium in the diet for Mx of osteoporosis?
700 mg of Ca2+ is required in most patients; post-menopausal women should aim their dietary intake at 1000 mg of Ca2+ per day
Portions of foot required for osteoporosis?
For 700 mg, 2-3 portions form milk and dairy)
For 100mg, 3-4 portions of calcium-rich foods
Non-dairy sources: • Bread and cereals (fortified) • Fish with bones • Nits • Green vegetables • Beans
Pharmacological treatment of osteoporosis?
Calcium & vitamin D supplementation
Bisphosphonate
Denosumab
Teriparatide
Strontium Ranelate
HRT
SERMS (selective oestrogen receptor modulators)
Testosterone
When is calcium and vitamin D replacement used for osteoporosis?
R-calcium and vitamin D supplementation can be used to reduce risk of non-vertebral fractures in patients at high risk of deficiency due to insufficient diet or limited sunlight exposure
If dietary calcium is adequate (>700 mg daily), Vitamin D only may be preferred as the osteoporosis treatment adjunct
Cautions with calcium supplementation?
Should not be taken within 2 hours of oral bisphosphonates
When is a patient automatically considered to be at risk of vitamin D deficiency?
If low exposure to sun (cultural or housebound)
Examples of bisphonphonates?
Alendronate
Risedronate
Zoledronic acid
Uses of bisphosphonates?
Prevent bone loss at sites vulnerable to osteoporosis
Reduce risk of hip and spinal fracture; reduce risk of fragility fracture by ~50% in patients with post-menopausal osteoporosis
Mechanism of action of bisphosphonates?
Anti-resorptive agent that are
analogues of pyrophosphate
They adsorb onto bone within the matrix and are ingested by osteoclasts, leading to cell death (so bone resorption is inhibited)
Filling of resorption sites with new bone increases BMD
Duration of bisphosphonate therapy?
For 5 years (if a vertebral fracture, 10 years)
After stopping, drugs stay in bone and the effect remains for 2-3 more years
Potential side effects of bisphosphonate therapy?
Osteonecrosis of the jaw
Oesophageal carcinoma
Atypical fractures
Administration of Zoledronic acid?
Once yearly IV infusion for 3 years:
• 5mg in 100ml of NaCl is given over 15 minutes
Potential side effect of Zoledronic acid and treatment?
Acute phase reaction (fever, flu-like, night sweats, rigors, diffuse MSK pain, GI effects, and eye inflammation)
Treat with paracetamol
What is Denosumab?
Fully human monoclonal Ab
Mechanism of action of Denosumab?
Targets and binds, with high affinity and specificity, to RANKL (receptor activator of nuclear factor-kB ligand)
Prevents receptor activation (RANK), which:
• Inhibits development and activity of osteoclasts
• Decrease bone resorption
• Increase bone density
Administration of Denosumab?
S/C injection every 6 months
Potential side effects of Denosumab?
Hypocalcaemia
Eczema
Cellulitis
There are no contraindication in severe renal impairment
What is Strontium Ranelate?
Anti-resorptive agent that is 3rd line for fracture risk reduction
It is not recommended when there is an alternative osteoporosis treatment available
Contraindications with strontium ranelate?
Hx of: • Thromboembolic disease • IHD • Peripheral arterial disease • Uncontrolled hypertension
What is Teriparatide?
Recombinant PTH that stimulates bone growth (rather than reducing bone loss), i.e: it is an anabolic agent
When is Teriparatide used?
> 65 years with T score < -4
T score of – 3.5 with >2 fractures
Aged 55-64 years with a T score of -4 or below with >2 fractures (plus intolerant/unsatisfactory response to oral agents)
When to pharmacologically treat a patient with osteoporosis?
In most patients, consider treatment with anti-resorptive therapy when:
• T-score ≤ -2.5
If ongoing steroid requirement of ≥ 7.5mg prednisolone for 3 months/more OR if there is a prevalent vertebral fracture:
• Consider treatment with T-score < -1.5
Direct effects of corticosteroids on bone?
- Reduction of osteoblast activity and lifespan
- Suppression of replication of osteoblast precursors
- Reduction in calcium absorption
Indirect effect of corticosteroids on bone?
Inhibition of gonadal and adrenal steroid production
Effects of glucocorticoids on calcium metabolism?
Kidney
Gut (reduced Ca2+ absorption)
Bone (decreased matrix synthesis resorption)
Pituitary
Fracture risk with steroids?
Is dose-dependent; there is a rapid loss of BMD in the 1st 6 months (partially reversible)
What is Paget’s disease of bone?
Excessive breakdown and formation of bone, followed by disorganized bone remodeling, i.e: there is abnormal osteoclastic activity that is then followed by increased osteoblastic activity
Aetiology of Paget’s disease of bone?
Uncertain but may be a viral, environmental or biochemical trigger in a genetically susceptible individual
Consequences of Paget’s disease of bone?
Abnormal bone structure with reduced strength, so increased fracture risk
Sites inv. with Paget’s disease of bone?
Monostotic (single site) or polyostotic (multiple sites)
Predominantly affects long bones, pelvis, lumbar spine and skull; does not affect fingers and toes (SPARING)
Occurrence of Paget’s disease of bone?
Rare <40 years and incidence increases with age
Presentation of Paget’s disease of bone?
Bone pain, deformity, deafness or compression neuropathies
Complication of Paget’s disease of bone?
Osteosarcoma (rare)
Ix and diagnosis of Paget’s disease of bone?
May be incidental finding on X-ray or isolated raised Alk Phos
Diagnose with:
• X-ray
• Isotope bone scan shows distribution
• Raised alkaline phosphatase with normal LFT
Treatment of Paget’s disease of bone?
With bisphosphonates, if pain not responding to analgesia
What is osteogenesis imperfecta?
Rare group of genetic disorders mainly affecting bone, with at least 8 types of varying severity
Most are secondary to mutations in type 1 collagen genes (COL1A1, COL1A2); also, most show autosomal dominant inheritance
Types of osteogenesis imperfecta and presentation?
Type I (mild) - may not present till adulthood
Types III and IV (very severe)
Type II (neonatal lethal - they have fractures in utero)
More severe forms present with childhood fractures
Causes of childhood fractures?
Most common is trauma
If “no Hx of trauma”, consider NAI
Rare cause is osteogenesis imperfect
Treatment of osteogenesis imperfecta?
No cure but can use:
• Fracture fixation
• Surgery to correct deformities
• Bisphosphonates
