Ageing and Metabolic Bone Conditions Flashcards
What happens to bone in osteoporosis, osteomalacia, paget’s?
- osteoporosis = low bone volume
- osteomalacia = abnormal mineralisation
- paget’s = high bone turnover
In osteomalacia what are the blood results?
- low calcium
- low phosphate
- high alkaline phosphatase
- high PTH
- low vitamin D
In Paget’s what are the blood results?
- very high alkaline phosphatase
In renal failure what are the blood results?
- low calcium
- high phosphate
- high alkaline phosphatase
- high PTH
- low vitamin D
In primary hyperparathyroidism what are the blood results?
- high calcium
- low phosphate
- high alkaline phosphatase
- high PTH
What is alkaline phosphatase?
- produced by osteoblasts
- marker of active osteoblasts
- also produced by liver
What happens in osteoporosis?
- blood results normal
- ratio of matrix to mineral remains the same
- only difference is reduced overall bone amount
What happens in osteomalacia?
- low calcium and low phosphate
- increased PTH
- increase in AP as bone broken down
What happens in Paget’s?
- everything normal except AP
- osteoblasts producing a lot of new bone
Who is at risk of getting osteoporosis?
- aged 40 onwards
- more common in women as have lower bone mass to begin with and bone loss sped up after menopause due to oestrogen loss (oestrogen inhibits RANKL)
How is osteoporosis diagnosed?
- DEXA
- expressed as T or Z score
- T = no. of s.d from mean young (30 years)
- Z = no. of s.d. from mean
What is osteopenia classified as?
- T scores between -1 and 2.4
What is osteoporosis classified as?
T score <2.5
What is the mechanism of osteoporosis?
- relative increase in resorption not matched by formation
- loss unevenly distributed
- primarily affects trabecular bone
Why is trabecular bone more susceptible to loss in osteoporosis?
- higher turnover than cortical
- greater SA
- in locations that has to respond to new stresses
What are the primary areas impacted by osteoporosis?
- vertebral bodies
- femoral neck
What are the different possible treatments for osteoporosis?
- calcium supplements
- vitamin D
- hormone replacement therapy
- selective oestrogen receptor modulator (raloxifene)
- bisphosphonates
- teriparatide
- denosumab
How do calcium supplements work?
- reduce negative calcium balance
How does HRT work?
- first choice in peri-menopausal women
- lasts 5 years
How does raloxifene work?
- only works on bone which is an advantage
- anti-oestrogenic for uterus and breast
How do bisphosphonates work?
- first line treatment
- drug absorbed onto bone surface and incorporated into matrix
- ends up precipitated onto surface
- osteoclast clamps itself down
- = osteoclast apoptosis
- also signals to osteoblasts to produce new bone and decrease expression of RANKL
What are the complications of bisphosphonates?
- giant osteoclasts (accumulate)
- osteonecrosis (dead bone)
- atypical fractures (sub trochanteric and femoral shaft, old osteocytes signal for remodelling)
- SO prevent by not taking for a few months
How does teriparatide work?
- recombinant PTH
- intermittent exposure increases osteoblast activity vs. osteoclast
How does denosumab work?
- monoclonal antibody
- binds to RANKL acting as decoy receptor
- stops RANKL signalling to osteoclasts to differentiate
- subcutaneous injection every 6 months
- inhibits formation of osteoclasts
