Drugs Affecting Bone Flashcards
Why is there a greater incidence of osteoporotic fractures in the vertebrae and femoral neck?
because more trabecular bone is remodelled than cortical bone and these sites have a higher density of trabecular bone
What alters bone remodelling?
age, load bearing exercise, hormones, drugs
What stimulates osteoblasts to RANKL?
PTH, calcitriol and IL-6
What stimulates osteoblasts to produce osteoid?
the cytokines released from the matrix when bone is broken down (IGF and TGF beta)
What is the action of oestrogen on bone remodelling?
oestrogen decreases osteoclast activity
What is the action of glucocorticoids on bone remodelling?
increases osteoclast activity and decreases osteoblast activity
What is the action of calcitonin on bone remodelling?
decreases activity of osteoclasts
In what ways does vitamin D increase plasma calcium?
increased intestinal absorption, decreased renal excretion, increased osteoclast activity
In what ways does PTH increase plasma calcium?
increasing vitamin D synthesis, mobilising calcium from bone, reducing renal excretion
What is osteoporosis?
reduction in bone mass more than 2.5 standard deviations below the norm for a healthy 30 year old woman
What is osteopaenia?
a less severe form of osteoporosis (1-2.5 standard deviations below the norm)
What bone changes are seen in osteoporosis?
trabecular thinning and loss of trabecular connectivity
Which antiresorptive agents are used to treat bone disorders?
bisphosphonates, oestrogen receptor modulators, RANKL inhibitors
Which bone anabolic agents are used to treat bone disorders?
PTH, calcium, vitamin D, calcitonin
What is the mechanism of action of bisphosphonates?
absorbed into bone matrix because they are an analogue of pyrophosphate and are then ingested by osteoclasts during bone resorption and cause apoptosis of osteoclasts
Why do bisphosponates only require administration once a week?
because they remain in the bone for a long period of time
What are the adverse effects of bisphosphonates?
oesophagitis and possible oesophageal cancer, atypical fractures and osteonecrosis of the jaw
What is the mechanism of action of raloxifene?
selective oestrogen receptor modulator - agonist at oestrogen receptor in bone and tissue and antagonist at oestrogen receptor in mammary tissue and uterus - decreases osteoclast proliferation, differentiation and activation and promotes osteoclasts apoptosis - increases life span of osteoblasts and osteocytes
What is the mechanism of action of denosumab?
it is a human monoclonal antibody which binds RANKL and inhibits its activity and therefore reduce osteoclast activity
What does PTH acutely promote?
osteoblast development and activity
What does PTH in continuous high exposure promote?
osteoclast activity
What are oral calcium used to treat?
as an adjunct therapy in osteoporosis
What are the side effects of oral calcium?
GI disturbances
What is vitamin D used to treat?
rickets, osteomalacia, hypoparathyroidism, chronic renal disease
