Disorders of Bone Health Flashcards
What is osteoporosis?
Progressive systemic skeletal tissue disease characterised by low bone mass and microarchitecture deterioration of bone tissue
What occurs due to osteoporosis?
Increased bone fragility and susceptibility to fractures
What is the natural deterioration of bone over time?
20 years = strong, healthy bone
50 years = decreases in trabecular thickness which is more pronounced for non-loading horizontal trabeculae
80 years = decrease in number of connections between vertical trabeculae, decrease in trabecular strength
Where does bone remodelling take place?
At distinct sites called bone remodelling units = 10% of adult skeleton is remodelled each year
What does bone remodelling contribute to?
Calcium homeostasis and skeletal repair
What role do bone cells play in remodelling?
Osteoclasts = activation and resorption Osteoblasts = form bone Osteoid = undergoes mineralisation
What are the regulating factors of osteoporosis?
Peak bone mass and bone loss
What are some contributors to peak bone mass, and when is it achieved?
Genetics (70-80%), body weight, sex hormones, diet, exercise, achieved by age 30
What are some determinants of bone loss, and when does it begin?
Sex hormone deficiency, body weight, genetics, diet, immobility, disease, drugs (glucocorticoids), occurs from age 45
Where are some common fracture sites in patients with osteoporosis?
Neck of femur, vertebral body, distal radius, humeral neck
How is bone density assessed?
BMD predicts fracture risk independently of other risk factors = most commonly measured using DEXA scans
What is the normal value for BMD?
Within 1SD of the young adult reference mean
What value of BMD is suggestive of osteopenia?
BMD >1SD below the young adult mean but <2SD below this value
What BMD is suggestive of osteoporosis and severe osteoporosis?
Osteoporosis = BMD >= 2SD below young adult mean Severe = BMD >= 2SD below young adult mean with fragility fracture
Which patients should be referred for a DEXA scan?
Patients >50 with low trauma fractures
Patients at increased risk of fracture based on risk factors
What patients with osteoporosis should be targeted for therapeutic intervention?
Those at high risk of low impact fractures
What are the SIGN 142 guidelines for osteoporosis based on?
Fracture risk = address risk factors for fractures (modifiable/non-modifiable), assessment of fracture risk
What are some non-modifiable risk factors for fractures in patients with osteoporosis?
Age, gender, ethnicity, previous fracture, family history, menopause <=45 years old, co-existing disease
What are some modifiable risk factors for fractures in patients with osteoporosis?
BMD, alcohol, weight, smoking, physical inactivity, pharmacological risk factors
How does the WHO risk calculator for fractures assess risk?
Calculation of absolute risk by incorporating additional risk factors = prediction of 10 year fracture risk of major osteoporotic fracture or hip fracture
What is used rather than BMD in patient’s under 20 with osteoporosis?
Z score
What patients are suitable for risk factor assessment?
Anyone >50 with risk factors, anyone <50 with very strong clinical risk factors (e.g early menopause)
When does risk assessment qualify osteoporosis patients for DEXA?
Anyone with a 10 year risk assessment for any osteoporotic fracture of at least 10%
What is investigated in patients with suspected osteoporosis?
U & Es, LFTs, bone biochemistry, FBC, PV, TSH
Consider protein electrophoresis/Bence Jones proteins, coeliac antibodies, testosterone, vitamin D, PTH
What are some secondary causes of osteoporosis?
Hyperthyroidism, hyperparathyroidism, Cushing’s disease, coeliac, IBD, chronic liver disease, chronic pancreatitis, CF, COPD, chronic kidney disease
What is some lifestyle advice for patients with osteoporosis?
High intensity strength training, low impact weight-bearing exercise, avoidance of excess alcohol and smoking, fall prevention
How much calcium should patients with osteoporosis aim to include in their diet per day?
700mg (2-3 portions)
Post-menopausal women aim for 1000mg to reduce fracture risk
What are some non-dairy sources of calcium?
Bread, cereals (fortified), fish with bones, nuts, green vegetables, beans
What are some drug treatments used for osteoporosis?
Calcium and vitamin D supplements, bisphosphonates, denosumab, teriparatide, HRT, testosterone
When should calcium and vitamin D supplements be considered?
To reduce risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake or limited sunlight exposure
What is the rule when taking calcium supplements and oral bisphosphonates?
Calcium supplements must not be taken within 2hrs of oral bisphosphonates
Is calcium supplementation needed if dietary intake in adequate?
No = only prescribe vitamin D in this case
What are bisphosphonates?
Analogues of pyrophosphate that absorb onto bone within the matrix = ingested by osteoclasts leading to cell death (inhibit bone resorption)
How do bisphosphonates improve BMD?
Filling of resorption sites by new bone increases BMD by 5-8%
What are some anti-resorptive bisphosphonates?
Alendronate and risedronate = reduce risk of fragility fractures by 50% in patients with post-menopausal osteoporosis
How do bisphosphonates help in osteoporosis?
Prevent bone loss in all sites vulnerable to osteoporosis, reduce risk of hip and spine fracture
What is the number needed to treat (NNT) of bisphosphonates for one year to prevent one fracture in osteoporosis patients?
T score less than -2.5 = 150
Plus existing fragility fracture = 30
What are the long term concerns of bisphosphonate use?
Osteonecrosis of jaw, oesophageal cancer, atypical fractures
What is an example of an IV bisphosphonate?
Zoledronic acid = once yearly IV infusion for three years
What is denosumab?
Fully human monoclonal antibody = targets and binds with high affinity and specificity to RANKL (receptor activator of nuclear factor-kB ligand)
What does denosumab inhibit?
Prevents RANK activation = inhibits development and activity of osteoclasts which decreases done resorption and increases bone density
How is denosumab administered?
Subcutaneous injection 6 monthly
What are some adverse effects of denosumab?
Hypocalcaemia, eczema, cellulitis
No contraindication in severe renal impairment
What is teriparatide?
Recombinant parathyroid hormone (1-34) = stimulates bone growth (anabolic agent)
When is teriparatide used?
In severe osteoporosis, particularly if high risk of vertebral fracture
When should medication be considered to treat osteoporosis?
Consider antiresorptive therapy when T score <= -2.5
When should medication be started to treat osteoporosis patients with a T score < -1.5?
If the patient is has ongoing steroid requirement >= 7.5mg prednisolone for 3 months or more
If there is prevalent vertebral fracture
What are the direct effects of corticosteroids on bone?
Reduction of osteoblast activity and lifespan, suppression of replication of osteoblast precursors, reduction in calcium absorption
What is the indirect effect that corticosteroids have on bone?
Inhibition of gonadal and adrenal steroid production
How do corticosteroids impact fracture risk?
Individual variability to glucocorticoids, dose-dependent (but no “safe” dose), rapid loss of BMD (30% in first 6 months), partially reversible on cessation
What occurs in Paget’s disease?
Abnormal osteoclastic activity followed by increased osteoblastic activity = causes abnormal bone structure with reduced strength and increased fracture risk
What are some features of Paget’s disease?
Unknown aetiology, Rare < age 40, incidence increases with age, may be single site (monostotic) or multiple sites (polystotic)
What bones are typically affected in Paget’s disease?
Long bones, pelvis, lumbar spine, skull
What are the signs and symptoms of Paget’s disease?
Bone pain, deformity, deafness, compression neuropathies, osteosarcoma may be rare complication
How is Paget’s disease diagnosed?
Using x-ray = may be incidental finding
May be isolated high alkaline phosphatase
What is the classic x-ray appearance of Paget’s disease?
Isotope bone scan shows expanded bone with coarsened trabecular pattern
What is osteogenesis imperfecta?
Rare group of genetic disorders mainly affecting bone = most are autosomal dominant, most are secondary to mutations of type 1 collagen genes (COL1A1, COL1A2)
How many types of osteogenesis imperfecta are there?
At least 8 types of varying severity = type 1 is mild, type 2 is neonatal (lethal), types 3 and 4 are very severe
What may be osteogenesis imperfecta be associated with?
Blue sclerae and dentinogenesis imperfecta
More sever forms present with fractures in childhood
Mild forms may not present until adulthood
What is the treatment options for osteogenesis imperfecta?
No cure = fracture fixation, surgery to correct deformities, bisphosphonates
