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
How does osteomalacia occur?
- insufficient calcium and phosphate to mineralise new bone osteoid
- = softer bones, bend/fracture more easily
- vitamin D deficiency causes
What does tetracycline labelling show in osteomalacia?
- low bone turnover state
- some areas no labelling
- some diffuse labelling
- some single line
What is the treatment for osteomalacia?
- vitamin D supplements
- dietary (increase calcium)
- sun/UV exposure
What foods contain calcium?
- milk, bread, beans, pulses
- dried fruit, green leafy vegetables
Who is at risk of Paget’s disease?
- mostly over 80 years
- some 50-80
- otherwise rare
What are the 3 phases of Paget’s?
1) Initially increases rate of bone resorption (lots of giant osteoclasts)
2) compensatory phase/proliferative (increased bone formation and accelerated disorganised deposition)
3) sclerotic (woven bone not properly replaced/remodelled and irregular thickened trabeculae)
Which bones are affected by Paget’s?
- pelvis
- femur
- vertebra
- skull
- tibia
(not symmetrical)
What is a later complication of Paget’s?
- osteosarcoma
What is osteosarcoma?
- most malignant of cancers
- usually in long bone
- often near knee
- can spread rapidly
- to prevent spread = remove affected bone part/limb amputation
How is Paget’s treated?
- bisphonate (oral 2-6 months then IV single infusion)
- calcium and vitamin D
- pain management
- surgery
What is sclerostosis?
- lack of sclerostin which normally inhibits osteoblasts when osteocytes are healthy
- autosomal recessive
- Van Buchem syndrome
How does sclerostosis present?
- excessive height
- resistance to fracture
- endosteal hyperostosis
