Osteoporosis Flashcards
Vitamin D (Calcitrol, ergocalciferol, cholecalciferol)
- three forms of the drug: cholecalciferol (sunlight), ergocalciferol (grains and fortified milk- converted to cholecalciferol for use), Calcitrol (most active form of vitamin D)
- Dosing determined by measuring 25-hydroxyvitamin D serum concentrations
- Long half life and levels don’t need to be very high, does not need to be taken at the same time as calcium
- Calciferol is preferred because it sustains blood levels for a longer time - Inc. circulation calcium by binding to nuclear receptor effecting gene regulation:
- activating osteoclasts thru RANK ligand- increased resorption
- stimulates collagen synthesis in osteoblasts
- increasing intestinal absorption of calcium and phosphate
- decreasing renal excretion of calcium and phosphate - Indications
- Vitamin D deficiency
- Ricketts
- Familial hypophosphatemia
- osteomalacia
- used as a nutritional supplement to ensure optimal calcium utilization - Adverse Effects
- inc in urine calcium- long term use could be potentially damaging to the kidney - CI
- sarcoidosis, kidney stones
PTH
Stimulated by low Calcium blood levels
Inc calcium levels by:
- increasing osteoclastic activity and number via RANK ligand
- Inc. renal ability to resorb calcium
- stimulates production of 1, 25 Vitamin D (active vitamin D)
Calcitonin (vitamin)
“Tones down calcium”
Inc when Calcium blood levels are high by:
- inhibiting osteoclast activity
Maintains bone in pregnancy and lactation
- stimulated by estrogen
Calcium
Doesn’t matter where the calcium comes (food, vitamins etc.)
MOA: inhibition of PTH secretions, and could alter the chemical properties of the bone- optimally mineralize
Indications: Adult men and women
Calcium alone cannot prevent osteoporosis but an adequate intake is needed for other treatments to work
- Elemental calcium is what is used by the body
- Calcium carbonate is the most cost- effective source of calcium
- No all calcium preparations are absorbed equally because of the different rates of dissolution
- Calcium is absorbed better when taken throughout the day- and should be taken at least twice a day
- One dose at bed time may prevent bone loss that occurs at night
Adverse Effects:
- Can inhibit iron absorption- separate the calcium and iron supplements and use calcium citrate
- Calcium can inhibit thyroid medication absorption- separate the intakes - thyroid- morning and calcium later
CI
- Sarcoidosis, kidney stones
Calcitonin (Miacalcin)
- salmon Calcitonin used
- Longer duration than human calcitonin
- Calcitonin inhibits bone resorption of calcium and phosphate by osteoclasts- both resorption and formation are reduced over time
- Antagonizes PTH
- Administered intranasally or injected (destroyed in GI) - Indications
- Prevent vertebral compression fractures
- reduces pain, esp back pain, even before a clinical change is seen in bone mass - Adverse Effects
- Allergic reactions - anaphylaxis
- rhinitis, sinusitis
- nausea vomiting - CI
- Fish hypersensitivity
- Breast feeding (can inhibit lactation)
Teriparatide
- Recombinant PTH hormone
- MOA is not fully understood,
- PTH stimulates osteoblastic and osteoclastic activity, drug provides intermittent spikes of PTH which increases bone formation and dec. bone resorption - Indications
- Reduces incidence of new vertebral and non-vertebral fractures
- AJ is really fucking cute
- Intermittent PTH therapy will reduce bone turnover, stimulate formation of new bone and increase bone mass
- Anabolic osteoporosis therapy* - inc. bone mass - useful in inc. bone density in pts with severely low bone mass
- Anabolic actions diminish with time: tx for 18-24 months, tx with anti-absorbing medication after discontinuation
- hypoparathyroidism - SC injection 1/day, serum concentrations peak 30mins after admin and gone within 3 hours
- SE
- increases serum calcium (hypercalcemia and hypercalciuria) and decreases serum phosphorus
- injection site rxns
- leg cramps
- Dizziness, nausea, headach - CI
- osteosarcoma (in rats), and in pts susceptible to osteosarcoma (pagets disease, radiation therapy, open epiphysis, history)
Denosumab
- Fully human, highly specific MAB against receptor activator of nuclear kappa - beta ligand (RANKL)
- MOA
- antibody to RANK ligand- the factor made by osteoblasts that is necessary for the formation of mature osteoclasts
- inhibits bone resorption - Indications
- FDA approved for osteoporosis tx in post - menopausal women and men at high risk for fractures
- increases bone mass and strength in both corticol and trabecular bone –> good choice for pts with any disease characterized by rapid bone resorption esp when resorption is temporary - SC injection 1 every 6 months, duration unknown
- SE
- hypocalcemia
- cellulitis, eczema
- bone and back pain reported
- osteonecrosis of the jaw in pts with metastatic cancer
- bone formation suppressed- may result in brittle bones (unknown) - CI
Absolute: hypocalcemia, pregnancy category X
relative: chronic kidney disease ( stage 4/5- gfr <30), pts with serious injections (RANK system used in lymphocytes- but has not been seen yet!), pts with serious chronic liver failure, children (may inhibit bone growth and tooth eruption)
Bisphosphonates (- dronate, dronic acid)
alendronate, risedronate, ibandronate, zoledronic acid
- Analogs of phyrophosphate (P-O-P bone replaces with non-hydrolyzable P-C-P bond)
- powerful drugs: used in pts with a high risk of fractures (reduce incidence of fractures and improve QOL)
- not used in pts with osteopenia - MOA
- inhibits osteoclast activity and bone resorption
- inhibits formation, aggregation, and dissolution of hydroxyA crystals by binding to calcium salts and replacing the phosphate, thus blocking HydroxyA
—- results in a calcium bisphosphonate crystal which inhibts osteoclast ability to form resorption pit—> denser bone —> increase strength - Indications
- First line tx for osteoporosis in men and post-menopausal women
- pagets disease
- prevent bone loss with multiple mylone and other osteolytic metastases from solid tumors - Different forms of drug
Oral administration (alendronate, risedronate, ibandronate, etidronate), absorption is very poor
- take 2 hrs before breakfast wo calcium or mg
- take with 1/2 cup of water
- remain upright for 30-60 mins to reduce GI irritation
IV Administration (zoledronic acid, pamidronate, etidronate)
- administer slowly or else renal toxicity
- co admin of Calcium and vit. D during therapy
- once/3months or once/year - SE
ORAL Admin: abdominal pain, GI irritation, esophageal ulcreation, constipation, diarrhea, and flatulence
IV admin: Renal toxicity if given to quickly
BOTH: N/V, mild hypocalcemia, afib, osteonecrosis of the jaw in pts following major dental work - CI
ORAL: do not take Calcium with oral- will inhibit absorption of bisphosphonates, also avoid oral in pts with esophageal disease, and bed rest pts who can’t stay upright for 1 hr
Cinacalcet
- Calcium receptor agonist
- MOA:
- Oral calcimimetic drug that binds to calcium sensing receptor- mostly in the Parathyroid gland
- Blocks PTH release - Indications
- tx secondary hyperparathyroidism in chronic kidney disease and parathyroid carcinoma
Vitamin D (endogenous)
released when Ca2+ levels are low
- induces osteoclast activity via RANK ligand
- stimulates Ca2+ absorption from the intestines
- increases resorption of Ca2+ from the kidneys
- Stimulates collagen synthesis in the osteoblasts
- works in conjunction with PTh
