B6.052 - CBCL Osteoporosis Prework 5 Mechanism of Osteoporosis Flashcards
primary causes of osteoporosis
defects in signaling
age related changes
endocrine related changes
impact of age on osteoporosis
osteoblasts have reduced proliferative and biosynthetic potential with age
impact of reduced physical activity in ostoporosis
reduced mechanical forces that normally stimulate normal bone remodeling
muscle contraction is dominant source of skeletal loading
resistant exercises such as weight training are most effective for increasing bone mass
genetics of osteoporosis
twin and family studies have shown that heritability of bone mass is 50-70%
single gene defects are rare but have large effecrs
polymorphisms associated with osteoporosis
genome wide association studies: top associated genes are RANKL, OPG, RANK
role of nutrition in osteoporosis
calcium nutritional state contributes to peak bone mass
calcium deficiency in adolescence/early adulthood restricts peak bone mass ultimately achieved
Vit D absorption and metabolism decline with age
endocrine influence on osteoporosis
post menopausal
acceleration of bone loss
decade after menopause: yearly reductions in bone mass up to 2% of cortical bone, 9% of cancellous bone
women may lose up to 35% of cortical bone and 50% of cancellous bone 30+ years after menopause
general estrogen influences on osteoporosis
decreased estrogen after menopause increases both bone resorption and formation bu the latter cant keep up with the former
estrogen impact on osteclasts
decreased estrogen appears to increase secretion of inflammatory cytokines
Increased RANKL, IL6, TNFa, IL1
decreased OPG, osteoblast diff, osteoclast apoptosis
inflammatory cytokines in bone remodeling
inflammation primarily promotes osteoclasts maturation and activity
TNFa, IL1, IL6
activated T cells secrete RANKL and TNF a
reduced estrogen after menopause, loss of anti inflammatory effects
what cytokines inhibit osteoblasts
TNFa, IL1, IL6
contributing factors to GIBL (glugocort induced bone loss)
direct effects on osteoclast and osteoblast
induction of secondary hypogonadism and HPTH impared vit D metabolism, muscle atrophy, hypercalcuria
high doses can stimulate osteoclastogenesis (increasess RANKL, dec OPG)
prednisone 5 mg / day can increase risk
therapy for steroid induced bone loss
treat underlying disease
reducing dose
kyphosis
can be d/t osteoporosis
dowagers hump
higher up in the back
lordosis
lower down there is a bump, think ass out
