Loco PBL 2: Osteoporosis Flashcards
What is osteoporosis?
Skeletal disease characterised by low bone density and micro-architectural defects in bone tissue leading to an increased bone fragility and a susceptibility to fractures
What is the epidemiology of osteoporosis?
50% of women over 50
What are the risk factors for osteoporosis?
Female, old age, BMI <19, malabsorption disorders, family history of hp fracture, long-term use of high dose oral steroids, hyperthyroidism and a reduced androgen level
Why does the menopause increase the risk of osteoporosis in women?
Reduced oestrogen production leads decreased inhibition of osteoclasts causing the ratio of degeneration to generation to become skewed leading to bone thinning and weakening
Where are the most common sites for osteoporosis-induced fracture?
Hips, vertebra and radius
What is the FRAX index used for?
To determine the 10 year probability of acquiring a hip fracture
What does a T-score used in a DEXA scan represent?
Compares individual’s bone mineral density against a healthy 30 year old’s
What does a Z-score used in a DEXA scan represent?
Compares individual’s bone mineral density against normal for someone of the same age and sex
What do the T-scores from a DEXA scan represent?
> -1 SD = normal; -1 to -2.5 SD = osteopenia;
What are the treatment options for osteoporosis?
Conservative management, HRT, selective oestrogen receptor modulators, bisphosphonates, raloxifene, denosumab or teraparatide
How may osteoporosis be treated conservatively?
With calcium, vitamin D and regular exercise
How may HRT be used in the treatment of osteoporosis?
In perimenopausal women for no more than 5 yearsq
How may raloxifene be used in the treatment of osteoporosis?
A form of selective oestrogen receptor modulator which prevents osteoporosis in post-menopausal women
What is the mechanism of action of raloxifene?
A form of selective oestrogen receptor modulator
What is the mechanism of action of bisphosphonates?
Directly inhibit osteoclasts by acting on intrinsic enzyme needed for them to breakdown bone
What are the potential side-effects of bisphosphonates?
Giant osteoclasts, osteonecrosis of the jaw, and atypical factors (subtrochanteric and femoral shaft fractures)
How may alendronate or risedronate be used in the treatment of osteoporosis?
Forms of bisphosphonates that can directly inhibit osteoclast activity
What is the mechanism of action of teriparatide?
A PTH analogue that can activate more osteoblasts than osteoclasts in certain doses
How may teraparatide be used in the treatment of osteoporosis?
A PTH analogue that can activate more osteoblasts than osteoclasts in certain doses
How may denosumab be used in the treatment of osteoporosis?
Binds to RANKL to prevent it from stimulating the activity and differentiation of osteoclasts; to prevent bone breakdown
What is the mechanism of action of denosumab?
Binds to RANKL to prevent it from stimulating the activity and differentiation of osteoclasts
What kind of tissue is bone?
Dense connective tissue
Which is the most common type of bone?
Cortical (80%), trabecular (20%)
What is a Haversian canal?
Cylindrical tubes which run down the axis of long bones to provide compressive strength
What is a Volkmann’s canal?
A horizontal branch of the blood vessels supplying the bone, branching from the periosteal blood vessels
Outline the composition of the bone matrix.
Type I collagen, proteoglycans, calcium hydroxyapatite on the collagen fibres (leading to hardness and rigidity)
Where are osteoprogenitor cells located?
Periosteum or endosteum
Which cells secrete sclerostin?
Osteocytes
What is the function of sclerostin?
Secreted by ‘happy’ osteocytes to inhibit osteoblasts
What is the role of PTH on bone metabolism?
Increases calcium uptake and phosphate excretion by the kidney, increases osteoclasts (due to PTH receptor on osteoblasts which then produce RANKL), increases synthesis of 1, 25 dihydroxyvitamin D from the kidney and increases gut absorption of calcium
What stimulates PTH release?
Low serum calcium levels
What is the role of calcitonin in bone metabolism?
Inhibits the differentiation of osteoclasts, increases calcium excretion and inhibits calcium gut absorption
What stimulates calcitonin release?
Normal/high serum calcium levels
What is the role of oestrogen in bone metabolism?
Increases calcium gut absorption and inhibits osteoclasts
What is the role of glucocorticoids in bone metabolism?
Decreases gut absorption of calcium, inhibits bone deposition and promotes resorption
How does PTH affect sclerostin production?
Inhibits sclerostin in mechanical stress which allows osteoblasts to be stimulated (which eventually activate osteoclasts)
How does calcitonin affect sclerostin production?
Upregulates sclerostin secretion to inhibit osteoblasts (to prevent them from activating osteoclasts)
