Drugs Affecting Bone Flashcards
Osteoid is made up by
Collagen, cytokines and growth factors
how much bone is remodelled per year in adults?
25% trabecular
3% cortical
osteoporosis occurs at sites of high [trabecular bone]
Neck of femur
Vertebrae
the reabsorption of bone causes the release of cytokines from the mineralised osteoid such as —1— and their function is to activate —-2—- and induce —3—
1 IGF and TGF-ß
2 Osteoblast
3 Bone deposition
hormones that decrease osteoclast activity include?
oestrogen, calcitonin
hormones that increase osteoblast activity?
PTH, embedded cytokines, calcitonin
some of the functions of calcitriol include?
Increases intestinal CA+2 absorption
Decreases renal excretion
Increases osteoclast activity
some of the functions of PTH include?
increases osteoblast production of RANKL
Decreases osteoblast production of Osteoprotegerin
Increases kidney hydroxylation of vitamin D to its active form
reduces renal Ca+2 excretion
some of the functions of calcitonin include?
decreases osteoclast activity (by inducing OPG production)
increases bone deposition
decreases Ca reabsorption from the kidney
What is the definition of osteoporosis?
reduction in bone mass of more than 2.5 SD bellow the norm for healthy 30yo women
[loss of both cells and matrix]
what is the definition os osteopaenia?
reduction in bone mass 1-2.5 SD bellow the norm for healthy 30yo women
what are some of the changes observed in osteoporosis?
trabecular thinning
loss of trabecular connectivity
what are the main two types of drugs used in bone disorders?
Block osteoclast Activity (Antiresorptive Agents)
Boost osteoblast activity (Bone Anabolic Agents)
Block osteoclast Activity (Antiresorptive Agents) include
*Biphosphonates
Selective oestrogen receptor modulators
RANKL inhibitors
Boost osteoblast activity (Bone Anabolic Agents) include
Vitamin D analogues
PTH
Ca+2
Vitamin D
how do biphosphonates work? [alendronate]
Deposited into bone by osteoblasts
Released and phagocytosed by osteoclast
induces apoptosis of the osteoclast and inhibits their recruitment
Biphosphonates are
Enzyme Resistant Analogues of pyrophosphate (P-O-P)
how often do biphosphonates need to be administered?
once a week but they persist in bone for a long time
patient must walk or be sited after ingestion (risk of oesophagitis –> lead to increased risk of oesophageal cancer if taken for more than 3 years)
once taken it is fo’life yo
how does oestrogen work?
Decreases reabsorption
Decreases differentiation and proliferation of osteoclasts
Promotes osteoclast apoptosis
oestrogen analogues increase bone mass T/F
F, just maintenance of left behind and slows bone loss
What medication is given instead of oestrogen (as it has a risk for cardiovascular complications and breast cancer?)
Selective Oestrogen Receptor Modulators (SERMs) [Raloxifene]
mechanism of action of SERMs
Agonist at cardiovascular tissue and bone
Antagonist at mammary tissue and uterus
Mechanism of action of RANKL inhibitors [denosumab]
binds to Receptor Activator of Nuclear Kappa Beta ligand (RANKL) to block its binding to RANK on osteoclasts (necessary for differentiation, survival and activity)
RANKL inhibitors are able to
decrease bone turnover and increase bone density
