Which type of bone is preferentially remodelled, trabecular or compact?
What is the major cause of hyperphosphataemia?
What is the pathophysiology of osteoporosis at a cellular level?
Increase activity and life span of osteoclasts
Decreased life span of osteoblasts and osteocytes
= Larger and deeper resorption cavities in bone = more fragile bone
How are biphosphonates administered?
Taken on a weekly basis
Which two bones are preferentially effected by pathological remodelling?
Head of femur
What is the effect of oestrogen on bone cells?
Decreases the activity of osteoclasts
What is the suggested long term treatment regiment for osteoporosis in females?
Start with HRT
Then Raloxifene + Bisphosphonates + PTH + Ca + Vitamin D + RANK-L inhibitors
What stimulates osteoblasts to express RANK-L?
How does oestrogen therapy effect bone mass?
Maintains bone mass
Slows bone breakdown
How can PTH therapy work to reduce bone density loss?
Because PTH treatment acutely increase osteoblast activity (whilst continuous high exposure of PTH favours bone catabolism)
What is an advantage of SERMs?
It is an antagonist of oestrogen receptors in mammary tissue therefore doesn't carry a breast cancer risk
What is the mechanism of action of bisphosphonates?
They are absorbed into bone
Osteoclasts that ingest them are inhibited and apoptosis is promoted
What type of drug is denosumab?
A monoclonal antibody RANK-L inhibitor therefore blocks the activation of osteoclasts
What type of drug is alendronate?
What is the specific definition of osteoporosis?
A reduction of bone mass by greater than 2.5 standard deviations for a 30 year old female
What are the two board classes of drugs used in bone disorders? What type of cells do they target
Anabolic agent: osteoblasts
What is the function of embedded cytokines?
Increase the activity of osteoblasts
What are the effects of calcitriol?
Increase osteoclast activity
Decrease renal excretion of Ca
Increase intestinal absorption of Ca
What are the major side effects of biphosphonates?
Oesphagitis risk - slight cancer risk
Atypical fracture due to remodelling effect
What are some bone anabolic agents?
Oral vitamin D analogue
What has replaced oestrogen therapy?
Selective oestrogen receptor modulators (SERMs)
What are downsides of oestrogen therapy?
Increase cardiovascular risk and breast cancer risk
What happens to the trabecular structure in osteoporosis?
Trabeculae are loss and others are thinned
What type of drug is Raloxifene?