Bisphosphonates and bone Flashcards
what is the composition of bone
10% water
20% collagen (gives strength)
70% HAP (gives hardness of bone)
also has blood vessels = bone can respond to stress
function of osteoclasts function of osteoblasts
clasts= resorb bone/ break it
blasts= make bone
what are the key hormones in bone remodelling process
what are some key molecules in the process?
hormones: eostrogen, para-thyroid hormone
molecules: cytokines, tumour factors, RANK-L, OPG
what is the process, step-by step, by which bone remodels?
osteoblasts lay down new bone, as they do they secrete RANK-L and OPG
osetoclasts have receptors for RANK-L and OPG, when ligands bind, osetoclasts become active and starts to dissolve bone.
the process is in homeostasis: equal bone laid down as bone dissolved
what is osteoporosis?
pores in bone
increase in fractures.
what are the risk factors for osteoporosis?
- AGE
- women- menopause
- long-term use of corticosteroids like hydrocortisone and prednisolone
how can osteoporosis be treated?
- healthy active lifestyle, vitamin d= less chance of getting severe osteoporosis
- hormone replacement therapy for menopausal women
- prescribe bisphosphonates!
(also given to myeloma pts)
what is a bisphosphonate molecule?
binds to HAP in bone via its 2 phosphate molecules, its OH group, and its R2 functional group.
how does a bisphosphonate interact with Ca2+ of HAP- structurally speaking?
calcium can form 4 bonds:
- one with phosphate 1 of the bisphosphonate
- one with the phosphate 2 of the bisphosphanate
- one with the OH group of the bisphosphonate
- one with the R2 functional group of bisphosphonate
changing the R2 group changes the affinity of bisphonates and gives rise to different ‘types’ of bisphophonates.
name which is given for osteoporsis and which for myeloma/cancer pts.
ALENDRONATE= given for osteoporsis, taken orally everyday. meduim strength.
ZOLENDROTE= give for cancer pts with bone metastasis (breast, prostate, lung) and myeloma pts (bone marrow cancer). strongest one.
how do bisphosphonates work?
they bind very strongly to HAP in bone which means its harder to dissolve bone AND bisphosphonates are toxic to many cells including osteoclasts and osteoblasts thus killing them!
why are bisphosphonates problematic for bone, even though they are given as a treatment for osteoporsis and bone cancers?
- reduce the activity of osteoblasts/clasts
- also toxic to other cells like fibroblasts/ keratinocytes
- reduce HEALING ability
- exposed bone cant heal (e.g. when extracting tooth)= produces an infection= painful, and may lead to pathological fracture (e.g. of the mandible)
what is MRONJ?
what was it called before?
medication related osteoporosis of the JAW!
(this medication includes bisphosphonates)
was BRONJ then was ARONJ
what are the risk factors for MRONJ
- depends why the pt. is taking the medication. higher risk if taking BP for cancer/myeloma
- depends on the type (weaker or stronger medications like bisphosphonates exist). alendronate- lower risk, zolendronate- higher risk
- how long been on medication: if a pt is on BP for less than 5 years= chance of getting MRONJ is 1/1000, but for longer than 5 yrs, the risk is higher
- steroid, smoking, age/menopause, untreated gum disease, alcohol also effect risk
- 60% of MRONJ happen AFTER recent dental extractions
myeloma is a cancer of the bone marrow.
we can also have cancers that metastasise to bone.
how do these link with hyper-calcemia?
the cancer will erode away at the bone= releases lots of ca2+= bone strength lost and causes pathological fracture and PAIN and hypercalcemia
its a medical emergency= can cause coma, kidney failure, cardiovascular problems
