Terms in this set (56)
What is osteoporosis?
Osteoporosis is a common disease of the bones & is often silent until a fracture occurs, making screening important.
Characterized by low bone mass & increased bone fragility.
Pateints are susceptible to fractures from minor traumatic events such as coughing, rolling over in bed, walking, or falling. Fractions include (1.5 million/year): vertebrae, forearem, & hip fractures.
Osteoporosis is most common in ________.
women with a majority of bone loss occuring within the first 5 years after menopause (2-3% per year) or stopping HRT.
However, osteoporosis is not just a disease of women.
What % of hip fracutres occur in men?
Osteoporosis in men is often associated with _______.
What is associated with a high mortality/morbidity rate & is the leading cause of nursing home placements?
Out of 100 hip fractures in persons >65 years old:
30 will die within 1 year
30 will recover fully
20 will require lifelong help with ADL's (walker, cane, etc.)
20 will require nursing home placement
What % of all body calcium is present in bone?
How do bones undergo continuous remodeling?
Old bone is resorbed, after which new bone is deposited.
The cells the resorb (chew-up) old bone are called osteoCLASTS & cells that deposit (build) new bone are called osteoBLASTS.
______ levels are calcium are tightly controlled.
Blood levels of calcium are tightly controlled. Preservation of serum calcium levels takes priority over the calcium requirements of the bones. Blood will always win over the bones!
How are calcium levels regulated?
1) intestinal absorption
2) renal excretion
3) resorption or deposition of calcium in bone
What factors control these regulation processes?
1) parathyroid hormone
2 vitamin D
When is Parathyroid Hormone released?
Released from the parathyroid gland in response to low levels of plasma calcium.
Explain the major functions of Parathyroid Hormone (PTH).
1) Continuous endogenous PTH release promotes calcium resorption from bone (moves Ca++ from bone to blood)
2) PTH inhibits renal excretion (loss) of Ca++ by promoting reabsorption of filtered calcium.
3) PTH activates vitamin D
How is vitamin D obtained?
Obtained through diet & exposure to sunlight. Vit D is converted into active from in response to low levels of plasma calcium. Vitamin D deficiency causes riskets & osteomalacia (soft, curved bones)
Explain the major functions of vitamin D.
1) Inhibits renal excretion (loss) of Ca++
2) Increases calcium absorption from the intestine
3) Promotes Ca++ resorption from bone (Although it promotes the removal of Ca++ from bone, overall there is NO NET LOSS of Ca++ from bone. This is because vit D increases serum Ca++ which will stimulate osteoclast activity)
When/Where is Calcitonin produced?
Calcitonin is a hormone produced by the thyroid gland in response to high levels of plasma calcium
Explain the major functions of Calcitonin.
1) Inhibits the resorption of calcium from bone (inhibits Ca++ removal from bone)
2) Increases renal exretion of calcium. (When used therapeutically, as long as adequate Ca++ intake occurs, overall there is an increase in bone formation)
What types of patients should you screen for Osteoporosis & Osteopenia?
Consider screening for pts with a strong family history, hypogonadal states, endocrine or GI disorders, corticosteroids, & high risk of falls.
Screen all women >/= 65 y/o & men >/= 70 y/o regardless of risk factors.
How is bone mineral density (BMD) measured?
BMD is measured using dual energy x-ray absorptiometry (DEXA) measurement of the hip & spine.
How is osteopenia defined? How is osteoposis defined?
Osteopenia is defined as T-score between -1.0 & -2.5.
Osteoporosis is defined as T-score below -2.5.
Who is Rx treatment advocated for?
Rx treatment is advocated for all patients:
1) with confirmed osteoporosis OR
2) confirmed osteopoenia plus a prior fracture OR
3) confirmed osteopenia plus a FRAX score indicating >/= 3% 10-year risk of hip fracture or >/= 20% 10-year risk of major osteoporotic fracture
How can one prevent osteoporosis & osteopenia?
Lifestyle modifications, adequate intake of calcium & vitamin D, fall prevention strategies
Explain the lifestyle modifications associated with prevention/treatment of osteoporosis/osteopenia. (diet & exercise)
1) Regular weight-bearing exercise (walking, dancing, stair climbing)
2) Diet: avoid excessive alcohol, caffeine, soda, high-fat foods, & avoid smoking
What are the fall prevention strategies?
1) vision screening & referral
2) home safety evaluation
3) medication review for drugs that increase fall risk
4) increase physical activity including balance & strength training specific for older adults
What are the main types of calcium supplements available?
Calcium carbonate (Tums, Viactiv, Oyster shell calcium - Os-Cal) & Calcium citrate (Citracal)
What are the advantages/disadvantages of the different calcium types?
Calcium carbonate: inexpenisve, take w/ food for best absorption.
Calcium citrate: more expensive but has the best oral absorption, especially in pts taking H2-blockers or PPIs.
What supplements should you tell patients to avoid?
Avoid expensive, "natural", or non-FDA regulated types of osteoporosis supplements such as shark cartilage, coral calcium, etc.
For full oral absorption, do NOT take more than _______ mg of calcium in a single dose.
What are the adverse effects/risks associated with calcium supplements?
Adverse effects include constipation & flatulence.
Taking excessive amounts of calcium does not further reduce risk but does increase risk of Ca++ based kidney stones & perhaps atherosclerosis.
What may also be included in calcium supplements?
vitamin D (very strong evidence & important)
vitamin K (some evidence linking to osteoporosis)
magnesium (very little evidence supporting a link)
Vitamin D deficiency is associated with ______.
reduced muscle & bone strength
What are the recommendations for vitamin D?
NOF suggests 400 IU/day for adults <50 y/o & 800-1,000 IU/day for adults >50 y/o.
Many experts recommend 800-2,000 IU/day in any adult (or a single weekly dose of 7,000-14,000 IU or 50,000 IU once monthly)
Vitamin D supplementation reduces falls by _____. (NNT)
NNT is 15 to prevent one fall (that's pretty darn effective)!
What are the adverse effects of vitamin D supplementation?
Symptoms of toxicity include N/V, anorexia, confusion, constipation, weakness, wt loss, hyperphosphatemia, hypercalcemia
Name the medication classes used to treat/prevent osteoporosis.
(Bisphosphonates, calcitonin & estrogen agonist/antagonist all prevent bone resporption. Increases in bone density are also seen; however, their main efficacy lies in preventing further bone loss)
Success of all osteoporosis medications requires ______.
sufficient calcium & vitamin D intake!
Name the Bisphosphonates.
alendronate (oral - daily or once weekly)
ibandronate (oral - Boniva - once monthly)
risedronate (oral - once weekly or monthly)
zoledronate (IV - once annually)
(etidronate, pamidronate, zoledronate all used IV for hypercalcemia)
What is the mechanism of action for the Bisphosphonates?
Bisphosphonates are incorporated into the bone. Osteoclasts cannot resorb bisphosphonate-bound bone. Osteoclast activity is therefore reduced.
What is the therapeutic use of Bisphosphonates?
Drugs of choice for treatment & prevention of osteoporosis. (Strongest evidence)
What are the adverse effects of Bisphosphonates?
Poorly absorbed from the Gi tract. Esophageal ulceration has occured. Bone pain.
Rarely: osteonecrosis of the jaw following tooth extractions & other invasive dental procedures. (can't remodel bone that has been damaged after dental procedures)
Explain the administration instructions of Bisphosphonates.
Take in the morning before breakfast, on an empty stomach.
Take with a full glass of WATER (not juice, tea, coffee, or anything else).
Remain upright for at least 30 minutes.
(Not recommended for pts who cannot remain upright for at least 30 minutes.)
Name the estrogen agonist/antagonist.
What is the mechanism of action for the estrogen agonist/antagonist?
It is an estrogen agonist in its effects of lipids & osteclasts.
It is an estrogen antagonist on breast & uterine tissue. Similar to drugs like tamoxifen. No increased risk of endometrial or breast cancer. It does not reduce other symptoms of menopause such as hot flashes.
What is the therapeutic use for the estrogen agonist/antagonist?
Treatment & prevention of osteoporosis in post-menopausal women AND also FDA approved to prevent breast cancer in women with estrogen sensitive breast cancer.
Raloxifene will NOT treat menopausal symptoms - it is not a simple estrogen alternative - there are differences.
What are the adverse effects of the estrogen agonist/antagonist?
Potential risk of thrombosis, just as with estrogen.
No problems with breakthrough bleeding or breast tenderness.
Stopping therapy will trigger a period of accelerated bone loss similar to that seen after menopause.
Explain the mechanism of action for Calcitonin. (nasal spray)
Same as the hormone. Decreases osteoclast activity & numbers. Increases osteoblast activity.
Explain the therapeutic use of Calcitonin.
Treatment & prevention of osteoporosis.
Treat pain associated with fractures.
(Doesn't work quite as well for hip fractures as Bisphosphonates)
What are the adverse effects of Calcitonin?
Considered very safe. Nasal dryness & irritation. Periodic nasal exam recommended.
Allergic reactions have been reported. Alternate nostril daily.
Name the Parathyroid Hormone medication.
teriparatide (SQ daily)
What is the mechanism of action for teriparatide?
Recombinant human parathyroid hormone (PTH). Endogenous PTH is a chain of 84 amino acids. Teriparatide is a chain of the first 34 amino acids. Intermittent administration of exogenous 1-34 PTH results in preferential BONE FORMATION.
Explain the therapeutic use of teriparatide.
Due to administration problems (daily injections) & high cost ($500/month) & long-term safety concerns, this drug is appropriate only for treatment of severe disease.
What are the adverse effects of teriparatide?
Studies in mice showed an increase in osteosarcomas. No safety data >2 years in humans.
Bone pain, weakness, leg cramps, orthostatic hypotension after injection.
Name the RANKL-inhibitor.
denosumab (SQ every 6 months)
Explain the mechanism of action of denosumab.
RANKL is a transmembrane or soluble protein essential for the formation, function, & survival of osteoclasts. Denosumab binds to RANKL & prevents it from activating its receptor (RANK) on the surface of osteoclasts. This inhibits osteoclast formation, function & survival, which in turn decreases bone resorption & increases bone mass & strength in bone.
Explain the therapeutic use of denosumab.
Reserved for treatment of postmenopausal women with osteoporosis at high risk for fracture or who have failed or are intolerant to other osteoporosis therapy
What are the adverse effects of denosumab?
Back pain, pain in extremities, hypercholesterolemia, musculoskeletal pain.
Increased risk of infection.
Localized injection site reactions.
Rarely: pancreatitis, osteonecrosis of the jaw.
Explain the evidence regarding calcium vs. placebo, calcium+drug vs. calcium alone or drug alone, etc.
There are few head to head trials comparing one prescription drug to another.
Ca++ alone reduces risk of fractures & increases bone density better than placebo but not as well as prescription options.
Ca++ plus a prescription drug is more effective than Ca++ alone & more effective than a prescription drug along.