B6.052 Prework 6: Osteoporosis Pharmacology Flashcards
prevention and treatment of postmenopausal osteoporosis
appropriate calcium and vit D intake (esp prior to achieving PBM)
exercise
pharm agents
pharm agents for osteoporosis
bisphosphonates
denosumab
teriparatide
raloxifene
effectiveness of Ca and vit d in treating osteoporosis
beneficial effect on bone density in postmenopausal women and older men
benefit on reduction of fracture rates is variable
vit D and Ca guidelines
vit D supplements: 1000 IU/d
Ca diet + supplements: 1000 mg
for adults over 65
types of bisphosphonates
alendronate- weekly
risedronate- weekly, monthly
ibandronate- monthly, IV every 3 months
zolendronic acid- IV annually
mechanism of bisphosphonates
direct inhibition of bone resorption
- concentrate at sites of active remodeling, remains in matrix until the bone is remodeled
- released in acid environment of the resorption lacunae and induces apoptosis in osteoclasts
- inhibits cholesterol biosynthetic pathway which contributes to anti-resorptive activty
adverse reactions with bisphosphonates
hypocalcemia
osteonecrosis of the jaw
atypical femur fractures
gastric symptoms
mechanism of denosumab
fully human monoclonal Ab to RANKL
binds/inhibits ability of RANKL to mature osteoclasts from osteoclast precursors (similar to OPG)
use of denosumab
twice yearly sc injection
if stopped, bone lost rapidly if another agent is not used
has applications in cancer treatment
adverse effects of denosumab
osteonecrosis of the jaw atypical femur fractures hypocalcemia skin infection (usually cellulitis of the lower extremity) derm reactions
raloxifene drug class
SERM
selective estrogen receptor modulator
how do SERMs work?
not “pure” agonists of estrogen receptor, have different effects in different tissues
-produce different structural changes in receptor upon binding, alters the co-factors with which ER interacts
mechanism of raloxifene
partially replaces missing estrogen post-menopause w respect to bone remodeling
less effect than seen with estrogens
effectiveness of raloxifene
reduces occurrence of vertebral fracture by 30-50%
no data for reduced risk of nonvertebral fractures over 8 years of observation
side effects of raloxifene
NO effect on heart disease, NOT associated with increased risk of uterine cancer/ benign uterine disease
65% reduction in invasive breast cancer (mainly decreased ER-positive)
effects of calcitonin
bone: -stimulates osteoblasts -inhibits osteoclasts kidney: -transient increase in Ca secretion
what is teriparatide
recombinant human PTH
amino acids 1-34 of the 84 AA endogenous PTH
mechanism of teriparatide
first approved anabolic agent
stimulates osteoblastic bone formation
with short duration of action, most likely activates osteoblasts without activating osteoclasts
effectiveness of teriparatide
increases predominantly trabecular bone at lumbar spine and femoral neck (less significant at cortical sites)
administration of teriparatide
administered once daily by subq injection in thigh or abdominal wall
use for 2 years in men and post menopausal women with osteoporosis
-followed w anti-resorptive agent to maintain BMD gain
-no fracture reduction benefit from second course of teriparatide
calcitonin administration
injection or nasal spray
what is calcitonin
32 ss peptide with sequence of calcitonin from salmon, 30x potency of human calcitonin
effectiveness of calcitonin
effects assessed by high res MRI
benefit in maintaining trabecular microarchitecture at multiple skeletal sites
reduced incidence of vertebral compression fractures by about 40% in osteoporotic women
on graph, drugs from best to worst
teriparatide PTH + estradiol alendronate estradiol raloxifene calcitonin
