treatment of OSTEOPOROSIS Flashcards
non-drug strategies to REDUCE BONE LOSS in postmenopausal women:
- dietary intake of → vit. D & Ca
- weight-bearing exercise & smoking cessation
- AVOID glucocorticoids
reasons to AVOID glucocorticoids for reducing of bone loss:
- antagonize vit. D-stimulated intestinal Ca transport
- stimulate renal Ca excretion
- block bone collagen synthesis
- increase PTH-stimulated bone resorption (?)
CALCIUM: (name of drugs)
- calcium carbonate → 400mg elementary Ca
2. calcium gluconate → 90mg elementary Ca
VITAMIN D: (name of drugs)
- vit. D3 → cholecalciferol
- vit. D2 → ergocalciferol
- 25-hydroxy D3 → calciferol
- 1,25-hydroxy vit. D3 → calcitriol
- 24,25- hydroxyl vit. D3 → secalcifediol
- alfacalcidol → undergoes hepatic hydroxylation → to calcitriol
VITAMIN D → mechanism of action:
- INTESTINE → increased Ca & P absorption by 1,25(OH)2 D
- KIDNEY → Ca & P excretion may be decreased by calciferol & calcitriol
- BONE → increased Ca & P resorption by calcitriol, bone formation increased by → secalcifediol
- regulation of PTH & insulin secretion
- modulation of cytokine production by macrophages & T-cells
- influence proliferation of other cells including cancer cells
VITAMIN D → indications:
- osteomalacia (in children → rickets)
- osteoporosis
- vit. D deficiency → due to malabsorption & liver disease (ergocalciferol)
- hypocalcemia ass. with hypoparathyroidism (ergocalciferol)
- osteodystrophy of chronic renal failure (calcitriol & alphacalcidol)
VITAMIN D → side effects:
HYPERCALCEMIA:
- constipation
- depression
- weakness
- fatigue
- reduced ability to concentrate urine → polyuria, polydipsia
- Ca deposit in kidney → renal failure & kidney stones
BISPHOSPHONATES: (name of drugs)
- etidronate & clodronate → NOT for osteoporosis
drugs for OSTEOPOROSIS:
- alendronate (2nd gen.)
- ibandronate (2nd gen.)
- risedronate (3rd gen.)
- zoledronate (3rd gen.)
drugs for disorders of BONE REMODELING:
- clodronate (1st gen.)
- etidronate (1st gen.)
- tiludronate
- pamidronate (2nd gen.)
BISPHOSPHONATES → mechanism of action:
- inhibition of recruitment & promotion of apoptosis of osteoclasts
- indirect stimulation of osteoblast activity
- ↑ bone mass → ↓ risk of fractures
- poorly absorbed from gut
- should be taken in vertical position 30min before meal, followed by 200ml water
BISPHOSPHONATES → indications:
- paget disease of bone
- malignant hypercalcemia
- multiple myeloma
- postmenopausal osteoporosis
- glucocorticoid-induced osteoporosis
BISPHOSPHONATES → CONTRAindications:
- severe renal impairment
2. bone necrosis
BISPHOSPHONATES → side effects:
- upset GI-tract → diarrhea, pain
- bone pain (musculoskeletal)
- esophagitis & esophageal ulcers → alendronate, risedronate & ibandronate
- long-term use etidronate → osteomalacia → ↑ risk of fracture (due to reduced calcification of bone)
CALCITONIN → mechanism of action:
- reduces bone resorption
2. relieve pain in osteoporotic fracture
CALCITONIN → indications:
- osteoporosis > 5y postmenopausal
- hypercalcemia & Paget ́s disease (by block bone resorption & ↓ serum calcitonin)
- recent vertebral fracture
CALCITONIN → CONTRAindication:
- rhinitis & other nasal symptoms
CALCITONIN → side effects:
↑ risk of malignancy → therefore reserved for pat. intolerant to other osteoporotic drugs
ESTROGEN: (name of drug)
HRT = hormone replacement therapy
ESTROGEN → mechanism of action:
- reduction of bone-reabsorbing action of PTH
- increase calcitriol in blood
- protect against fractures at hip & spine
- the increased 1,25(OH)2 D levels in vivo following estrogen treatment → may result from decreased serum Ca & P + increased PTH
ESTROGEN → indications:
- menopausal symptoms
- osteoporosis in pat. <60y.
- early menopause
SERM’s → name of drug: (selective estrogen receptor modulators)
- raloxifene
SERM’s → mechanism of action:
- estrogen-like effect on bone
- estrogen ANTAGONIST effect on breast & endometrium → ↑ bone density WITHOUT risk of endometrial cancer
- ↓ risk of invasive BC
- ↓ level of total & LDL cholesterol
SERM’s → indications:
- alt. to BISPHOSPHONATES in postmenopausal osteoporosis
2. prevention & treatment of osteoporosis
SERM’s → side effects:
- hot flashes
- leg cramps
- risk of venous thromboembolism → similar to estrogen
PTH → name of drug:
- teriparatide
PTH → mechanism of action:
stimulates bone formation → by stimulating osteoblastic activity in bone remodeling
PTH → indications:
- secondary parathyroidism
- parathyroid cancer
- primary hypoparathyroidism
- pat. at high risk of fractures
- pat. who failed or cannot tolerate other therapies
PTH → side effects:
- nausea
- vomiting
- loss of appetite
- muscle pain
- hypocalcemia
STRONTIUM RANELATE: (general info)
- antiresorptive drugs → ONLY effective in bones with high turnover
- effective independently of rate of bone turnover
STRONTIUM RANELATE → indications:
- postmenopausal osteoporosis
- senile osteoporosis (all types of osteoporotic fractures)
- can be long-term applied
STRONTIUM RANELATE → side effects:
- nausea
2. diarrhea
denosumab = prolia: (general info)
- Ca2+ level MUST be controlled → highest risk of HYPOCALCEMIA at 10-14 days after administration
- SC injection → every 6 months
denosumab → mechanism of action:
monoclonal antibody → targets receptor activator of nuclear kappa-B ligand & inhibits osteoclast formation & function
denosumab → indications:
- postmenopausal osteoporosis in women at high risk of fracture
- those intolerant or unresponsive to other therapies
- bone metastases
- MALES with hormonal ablation & osteoporosis
denosumab → side effects:
- infections, cataract
- constipation
- atypical bone fractures
- dermatological reactions
- hypocalcemia
- osteonecrosis of jaw