Osteoporosis Flashcards
Osteoporosis progression is?
clinically silent!!
- BMD (bone mass density) determined by DEXA
- BMD is expressed a T-score!!
- T-score: -1 to -2.5 - osteopenia
- T-score: -2.5 to -4- osteoporosis
Drugs’ efficacy for prevention and treatment of osteoporosis depends on?
-adequate intake of vit D and Ca!
Calcium Supplements
- Calcium carbonate- needs acid to dissolve and for abs
- Calcium citrate- doesnt need acid; higher cost
what promotes intestinal Ca absorption?
-1,25 (OH)3 Vit D3!!!
Vit D requirement
(normally 400-800/day) > 800/day in persons: -GI malabs disorders -corticosteroids, anticonvulsants, loop diuretics, heparin -less exposure/response to sunlight
Drugs that lower serum Ca (secondary causes of osteoporosis)
- glucocorticoids- impairs Vit D abs and impairs metabolic act in liver and kidney
- anticonvulsants (carbamazepine, phenytoin)- induction of p450- hepatic inact of vit D
- loop diuretics (furosemide)- Ca wasting
osteoporosis- risk factors
- genetics (FH)
- F > M
- post-menopausal (estrogen level)
- white, asian
- small and thin
- smoker, no exercise, alcohol
- drugs, poor diet, eating disorder
osteoporosis- pharmacology
- SERMs
- Bisphosphonates
- Biologicals
- Ab’s
SERMs- drugs
- Raloxifene
- Tamoxifen
Bisphosphonates- drugs
-Alendronate
-Ibandronate
-Pamidronate
-Risedronate
-Zoledronate
(AIPRZ)
Biologicals
- Teriparatide
- Calcitonin
- Ab’s- Denosumab
Anti-Resorptive Therapy- inhibit osteoclasts- what drugs??
- SERMs
- Bisphosphonates
- Biologicals
Anabolic therapy- act osteoblasts- what drugs?
-Teriparatide!!!!!
Postmenopausal women- prevention of osteoporosis
Estrogen H replacement!!
- balance bone resorption and bone formation
- optimal maturation of osteoclasts
Estrogen def- does what?
imbalances bone resorption and formation
-excess maturation of osteoclasts- excess bone resorption
HRT
-conjugated estrogens + medroxyprogesterone
Hormone Replacement Therapy- benefits, risks
Benefits -inc bone health, dec menopause sx's Risks -inc breast and uterine cancer -inc heart attack, stroke, thrombosis
SERMs- drug
-Raloxifene
SERMs- moa
- recapitulate estrogens actions in bone
- agonists at ER in osteoclasts!!!
- antagonists at ER in breast epit!!
SERMs vs HRT- risk vs benefits
- Raloxifene- used for breast cancer prophylaxis!!!!
- HRT- inc risk of breast, ovarian cancer
- both prevent/treat osteoporosis in postmenopausal women
Tamoxifen- risk of?
-inc uterine bleeding and cancer!!!
HRT estrogens, Raloxifene, Tamoxifen- SE’s of all
-venous thromboembolism risk
Bisphosphonates- moa
- sequestered by bone near remodeling sites
- accum in osteoclasts- inhibit osteoclast fxn:
- inhibit FPP (Farnesyl Pyrophosphate) synthase- inhibit Prenylated G proteins (inhibit signal transduction)
- osteoclast act and survival requires G-protein prenylation
Bisphosphonates- complications
- contraindication- pre-existing hypocalcemia
- SE- esophagitis, esophageal ulcer!!
- osteonecrosis of jaw (ONJ)
- long-term use- inc fractures- BP remain in bone for decades!!!
