calcium and bone Flashcards
osteoporosis: define osteoporosis, recall the risk factors and treatment options
clinical features of osteoporosis
loss of bony trabeculae -> reduced bone mass -> predispostion to fracture after minimal trauma (no pain but vulnerable to fracture)
what happens to bone mass with age
reduces
define osteoporosis
bone mineral density greater than or equal to 2.5 standard deviations below average value for young healthy adults (T-score -2.5 or lower); osteopenia if between -1.0 and -2.5
what does bone mineral density predict
future fracture risk
what measures bone mineral density and 2 locations
DEXA (dual energy x-ray absorptiometry) of femoral neck and lumbar spine
how does DEXA measure bone mineral density
mineral (Ca2+) content of bone measured (more mineral, greater bone density); gives T-score
osteomalacia vs osteoporosis
osteomalacia: vitamin D deficiency in adults causing inadequately mineralised bone, with an abnormal serum biochemistry (low 25(OH) vit D, low/nomral Ca2+, high PTH due to secondary hyperparathyroidism); osteoporosis: bone reabsorption (osteoclast) exceeds formation (osteoblast), decreased bone mass, normal serum biochemistry so diagnosis via DEXA
5 pre-disposing conditions for osteoporosis
postmenopausal oestrogen deficiency, age-related deficiency in homeostasis (men and women), hypogonadism in young women and men, endocrine conditions, iatrogenic
how does postmenopausal oestrogen deficiency predispose for osteoporosis
oestrogen deficiency leads to loss of bone matrix, causing subsequent increased risk of fracture
example of age-related deficiency in homeostasis (men and women) causing predisposition to osteoporosis
osteoblast senescence
3 examples of endocrine conditions which cause predisposition to osteoporosis
Cushing’s syndrome, hyperthyroidism, primary hyperparathyroidism
2 examples of iatrogenic conditions causing predisposition to osteoporosis
prolonged use of glucocorticoids, heparin
4 treatments for osteoporosis
oestrogen/selective oestrogen receptor modulators for postmenopausal women, bisphosphonates, denosumab, teriparatide
what is used to treat postmenopausal oestrogen deficiency as predisposing condition for osteoporosis, and how does it work
oestrogen hormone replacement therapy as has anti-resorptive effects on skeleton, preventing bone loss
why do postmenopausal women with an intact uterus need additional progestogen in hormone replacement therapy, as well as oestrogen, to prevent/limit osteoporosis
prevent endometrial hyperplasia and cancer
2 reasons why uses of oestrogen hormone replacement therapy is short term option when treating postmenopausal women
increased risk of breast cancer, venous thromboembolism
what do bisphosphonates do
bind avidly to hydroxyapatite and are ingested by osteoclasts, impairing ability of osteoclasts to reabsorb bone and impairing bone turnover
2 ways bisphosphonates impair ability of osteoclasts to reabsorb bone
decrease osteoclast progenitor development and recruitment, promote osteoclast apoptosis
4 uses of bisphosphonates
osteoporosis (first line treatment), malignancy with associated hypercalcaemia (also reduces bone pain and return [Ca2+] to normal), Paget’s disease (reduce bony pain), severe hypercalcaemic emergency
administration of bisphosphonates in severe hypercalcaemic emergency
i.v. initially, but rehydration first
pharmacokinetics of bisphosphonates: administration and absorption
orally active but poorly absorbed, so take on empty stomach when sitting up (food, especially milk, reduces drug absorption generally)
pharmacokinetics of bisphosphonates: where do they accumulate and how long do they last for (including negativity for young people)
accumulates at site of bone mineralisation and remains part of bone until reabsorbed (months, years), which may not be useful in younger patient
3 unwanted actions of bisphosphonates
oesophagitis, osteonecrosis of jaw (made adynamic, so have dentla work before starting bisphosphonates), atypical fractures
what may be required to prevent oesophagitis when using bisphosphonates
switch from oral to i.v. preparation
when is osteonecrosis of jaw a greater risk when using bisphosphonates
when receiving it i.v.
what may atypical fractures reflect in use of bisphosphonates
over-suppression of bone remodelling in prolonged use
what is denosumab molecularly
human monoclonal antibody
what does denosumab do
binds RANKL, inhibiting osteoclast formation and activity, thus inhibiting osteoclast-mediated bone resorption
how and when is denosumab administered to treat osteoporosis
subcutaneous injection 6 months/yearly, but is secondary to bisphosphonates
what is teriparatide
recombinant PTH fragment (amino-terminal 34 amino acids of native PTH)
what does teriparatide do
increases bone formation and bone resorption, but formation outweighs resorption due to dose
how and when is teriparatide administered to treat osteoporosis, and why
daily subcutaneous injection, but 3rd line treatment as very expensive
