Osteoporosis Flashcards
FRAGILITY FRACTURES
i) what is it?
ii) name two of the biggest problems with FFs
iii) give two reasons why people get FFs?
i) fracture caused by a fall from a standing height or less
or a spontaneous fracture (not due to malignancy)
ii) very common and costly
iii) reduced bone mineral density or alteed bone architecture
FRAGILITY FRACTURES
i) which scan can be used to look at bone mineral density? which two scans can be used to look at altered bone architecture
ii) mutations in which protein can cause change to bone material property?
iii) which structure can be visualised by X-ray cyrstallography? is this used in clinical practice?
iv) how may diabetes affect the bone? which protein does it impact?
v) name another way to investigate bone density apart from bone scan
i) BMD = DEXA
architecture = DEXA and high res quatitive CT
ii) mutations in type I collagen > insufficient or abnormal collagen
iii) see altered hydroxyapetite crystal structure - not used in clinical practice
iv) diabetes > glycation of end products (changes to collagen) > normal bone density but higher fracture rate due to alteration of collagen
v) microindentation
MAKING BONES STRONGER
i) how does fluoride tx affect bone density? does this improve fracture rate?
ii) which substance has a similar structure to pyrophosphate and has shown to decrease fracture rate in humans?
i) fluoride increases bone density but does not improve fracture rate
ii) etidronate > decreases fractures > can alter sie chains to make it more effective eg alendronate
PHYSIOLOGY OF BONE RESORPTION
i) what does an osteoblast express? what cell does this bind its receptor on?
ii) what does this ligand receptor binding cause?
iii) which cell is OPG produced by? what effect does OPG have?
iv) which monoclonal antibody can mimic OPG? how does this work? is it specific?
i) OBlast expresses rank ligand that binds rank R on osteoclast precursor
ii) rank lig receptor binding causes the osteoclast to mature and break down bone
iii) OPG is produced by osteoblasts > captures rank ligand to decrease effects on osteoclast (less bone breakdown)
iv) denosumab > captures rank ligand and stops oclast being stimulated - very specific
DENOSUMAB
i) is it a human or mouse MAB?
ii) what does it do? what does it act as?
iii) does it have a long or short half life? how is it given?
iv) name three type of fractures it may reduce?
v) which system is it cleared by?
i) fully human MAB
ii) captures rank ligand and stops oclast being stimulated > acts as a decoy receptor
iii) long half life > given by SC injection
iv) can reduce spine, non spine and hip fractures
v) cleared by reticuloendothelial system
SCLEROSTEOSIS
i) which gene is mutated? which cell is it found in?
ii) how do bones appear in these individuals?
iii) what effect does the gene have on the wnt signalling system? what does this lead to?
iv) how can this be harnessed to stop bone breakdown?
i) SOST gene > found in osteocytes
ii) thick strong bones
iii) SOST gene produces scleorostin that inhibits the wnt sign system
- this leads to a decrease in oblast activity and reduced bone build up
iv) want to block sclerostin activity so that wnt is not inhibited therefore bone build up is promoted
ROMOSOSUMAB
i) what is this a monoclonal antibody against?
ii) which signalling pathway does this promote the activity of? what does this cause in relation to bone formation?
iii) is it more, equal or less effective than alendronate?
i) MAB against sclerostin
ii) promotes wnt signalling as sclerostin is an inhibitor of wnt
- increases bone building
iii) more effective than alendronate
SENESCENT CELLS
i) which protein can be released by senscent cells? what does this protein do?
ii) what did genetic deletion of this protein in neutrophils and MPs do?
iii) which treatment can therefore be given?
i) grancalcin > represses osteogenesis and promotes adipogenesis
ii) deletion > slows skeletal ageing
iii) give.a MAB to grancalcin (grancalc neutralising antibody treatment) > improves skeletal health during ageing
