Flashcards in Pharmacology of Osteoporosis Deck (19):
Where is bone mineral density (BMD) typically measured to predict osteoporosis? What is the measure at which osteoporosis is diagonsed?
Femoral neck (predicts risk of hip fractures), or the spine
2.5 standard deviations below the mean for young women in BMD
What are the recommendations for vitamin D and calcium supplementation? Give the exact values you want to hit?
Generally only needed in those nutritionally deficient, which is easy to be when taking antiresorptive agents (prevent freeing of calcium from bone) like those used for osteoporosis
1000mg of Ca for adults, with 1200mg if <50 in women
600 IU of vitamin D for adults, with 800 IU if <70 in women
What are the adverse effects of calcium supplementation? How is it given?
Only increased risk of kidney stones and GI distress
- generally given as calcium carbonate or citrate with food
What are the bisphosphonates and their mechanism of action?
Drugs ending in -DRONATE, prevent or treat osteoporosis by decreasing bone resorption by binding active sites of bone remodeling on osteoclasts (osteoclasts will grab drug instead of hydroxyapatite)
Most of the bisphosphonates are given orally. Which is not? What do these serve to do?
Zoledronic acid is given once yearly via IV, or once every two years to prevent osteoporosis
Reduce the risk of vertebral and non-vertebral fractures
When and how should bisphosphonates be taken?
Oral agents such as alendronate should be taken after an overnight fast with plain water, since many things can limit their absorption
They should also be taken upright to prevent the upper GI side effects
What are the common side effects of bisphosphonates? More severe?
Upper GI side effects: esophagitis, acid reflux, esophageal ulcers (think of the rusty rod in the neck of the dino).
Also common: hypocalcemia due to antiresorptive properties (supplement with vitamin D and Ca+2)
Severe: Osteonecrosis of jaw (jaw falling off dino), esophageal cancer
Which drug is a monoclonal antibody to RANKL expressed on osteoblasts, which stimulates osteoclast differentiation?
Denosumab (think dino-suit-man taking away crank-drill (RANKL) from the osteoclast kid)
How are the side effects of Denosumab different from bisphosphonates?
Allergic reactions at injection site, and also denosumab is safe in impaired renal function (bisphosphonates can cause acute renal failure)
Otherwise, the same minus the GI side effects
What drugs are the selective estrogen receptor modulators (SERMs)?
Includes Raloxifene (think relax in Sketchy) and Bazedoxifene
How do the SERMs work?
They are agonists of estrogens in bone (inhibits osteoclasts) -> relax sign inhibiting osteoclasts
They also have less cancer risk than normal estrogens because they antagonize estrogen action in the breast and uterus (can be used as chemotherapies for these cancers)
What are the side effects of SERMs?
Hot flashes, peripheral edema (fluid retention like all estrogens), increased risk of venous thromboembolism (same clotting propensity increase as estrogens)
What is the mechanism of action of Calcitonin and why is it rarely used for osteoporosis now?
Directly inhibits osteoclasts (reduce calcium levels) and causes excretion of Ca+2 in the kidneys (reduce calcium levels).
Mainly used in hypercalcemia
-> rarely used due to serious allergic reactions and increased risk of malignancy
What are the mechanisms of action of parathyroid hormone? Think bone and kidney. What inhibits it?
1. Stimulates osteoblasts and short-term bone formation
2. Long-term, stimulates osteoblasts to recruit new osteoclasts for bone breakdown and an increase in blood calcium
3. Parathyroid hormone stimulates reabsorption of calcium in exchange for phosphate in the kidney
4. Parathyroid hormone stimulates conversion to calcitriol in kidney
-> PTH is inhibited by high calcium levels and vitamin D
How is active vitamin D made?
7-DHC in skin is converted to vitamin D3 in skin (or D3 / D2 eaten in diet)
D3 converted to 25-OH-D3 in liver.
25-OH-D3 converted to 1,25-OH-D3 (calcitriol, active) in kidney, under control of PTH
What are the actions of active vitamin D?
Stimulates calcium and phosphate reabsorption in the kidney
2. Stimulates osteoblasts and stimulates osteoclasts, increase bone turnover
3. Blocks PTH (reduces bone breakdown overall)
4. Increases intestinal absorption of calcium and phosphate
What drug is a PTH analog and how does it treat osteoporosis?
Teriparatide (TA in sketchy), think Terry PARA
Once daily injections in short bursts will promote osteoblast bone formation without stimulate of osteoclast bone degradation
-> not an antiresorptive agent
Also acts in kidney
What are the most likely adverse effects of teriparatide?
Hypercalcemia and hypercalciuria -> bone resorption is not inhibited, and teriparatide also enhances resorption of Ca+2 in the kidney like PTH + stimulates vitamin D production