drugs affecting bone Flashcards
what are the metabolic and synthetic functions of bone?
reservoir for body’s calcium (99%) and phosphate (85%) deposits.
plays a role in acid-base buffering in response to large systemic perturbations.
synthesizes RBC and WBC’s.
impact of tetracycline on bone?
if tx with tetracycline is initiated during early development it will bind to calcium ions within dentin of teeth and cause yellow-brown discolouration of teeth (when exposed to uv light).
which component of bone is esp affected by processes/drugs that impact on remodelling?
trabecular bone (esp femoral neck and vertebral bodies).
NB: bone is 80% cortical and 20% trabecular (spongy, cancellous bone). Although trabecular bone makes up a larger surface area.
what is the normal rate of bone remodelling/year
10% (25% trabecular turnover, 3% cortical bone turnover)
what are the 5 phases of bone remodelling?
activation, resorption, reversal, formation, quiescence.
osteoprotegrin (OPG) is a soluble receptor for […..], which can be membrane bound or soluble. The balance between OPG and […..] determines the skewing of osteoclastic activity vs inhibition.
Upstream of this pro-resorbtive cytokines, esp [….], are the principal effect of osteoclastic differentiation.
RANKL
RANK
Nfkb
what effect does dexamethason (corticosteroid) have on bone remodelling?
DEX decreases OPG-L levels and increases RANKL
–>increased binding of RANK-L to RANK –>increased bone breakdown.
how does PTH impact bone mineralization?
increases plasma Calcium by
- increasing calcitriol (vit D) synthesis
- mobilizing calcium from bone
- reducing Ca excretion by the kidney
where does calcitonin come from and how does it impact bone mineralization?
thyroid gland
decreases osteoclast activity and calcium resorption from bone.
reduces renal reabsorption of calcium. (more excreted)
vitamin d/calcitriol impact of bone mineralization? where is it made/activated?
vit D dietary precurors converted to calcitriol in kidney.
calcitriol increases plasma calcium increasing intestinal aborption, decreasing renal excretion, increased osteoclast activity.
describe osteoporosis and RF’s?
reduction in bone mass more than 2.5 SD below the norm for healthy 30 yr old women.
RF;s:
post menopausal
ageing
following glucocorticoid therapy
NB: may be preceded by a state of Osteopaenia, whereby normal 30yr old women are 1-2.5 SD below the norm.
how does osteoporosis impact bones?
reduces bone mass by loss of cells and matrix.
reduces cross-sectional area of trabeculae so that loads on bone are relatively greater.
what is bisphophonate? how is it used in tx of bone disorders?
Anti-resorptive agent. Gets incorporated into the bony matrix and is less succeptible to enzymatic degradation than it’s analog, inorganic pyrophosphate.
inhibit recruitment of osteoclasts and promotes apoptosis of osteoclasts when its phagocytosed by osteoclasts during resorption.
Why are SERM’s used instead of hormone (estrogen) replacement therapy?
oestrogen replacement increases risk of CV death and breast cancer.
what are SERM’s? how is it used in tx of bone disorders?
selective estrogen receptor modulators (SERMs).
replaced HRT in treatment of osteoporosis.
Raloxifene is a stand out drug in this class. It acts as an agonist at estrogen receptors in bone and cardiovascular tissue. BUT an antagonist at estrogen receptors in mammary tissue and uterus.
estrogen decreases bone resorption by decreasing osteoclast differentiation, proliferation, activation, and promoting their apoptosis; while increasing the lifespan of osteoblasts and osteocytes.
NB: It does not increase bone density, but works to maintain it and slow the loss of bone mass.
