Osteoporosis Topic Preparation (slide 25 for the drugs)

Calcium can decrease the bioavailability of certain antibiotics - e.g.?

(eg, fluoroquinolones, tetracyclines) ALSO levothyroxine

Recommended daily intake of calcium for 51-70 y (men) as a measure to prevent osteoporosis.

1000 mg Elemental Calcium

Recommended daily intake of calcium for 51-70 y (women) as a measure to prevent osteoporosis.

1200 mg Elemental Calcium

Recommended daily intake of calcium for > 70 y (men) as a measure to prevent osteoporosis.

1200 mg Elemental Calcium

Recommended daily intake of calcium recommended for > 70 y (women) as a measure to prevent osteoporosis.

1200 mg Elemental Calcium (same as men > 70 y.o)

Limit treatment with Teriparatide to _____________ years

2 years maximum lifetime treatment; b/c safety beyond that point hasn't been studied

It is important to read product labels to prevent exceeding daily calcium intake of ____________________; what could happen?

2500 mg per day, which could cause hypercalcemia or kidney stones.

Ibandronate brand name

Boniva

COMMON Adverse effects of Calcium supplements?

Constipation, bloating, and flatulence are common adverse events of calcium supplements.

Raloxifene MoA

A selective estrogen receptor modulator; it has agonist properties on estrogen receptors in *bone* and lipids, along with antagonist properties in the breast and uterus.

First-line therapy for the treatment of osteoporosis among postmenopausal women

Bisphosphonates -> are incorporated into the bone and have a long half-life of years.

Biphosphonates MOA

Bisphosphonates target osteoclasts -> decrease the activity and survival of these cells

Recommend daily dose of Calcium carbonate (w/ food or w/o) in a patient taking PPI or H2 blocker.

If a patient is taking a proton pump inhibitor or acid suppressant, then calcium carbonate may not be appropriate as it requires acid-dependent disintegration and dissolution. In this situation, an alternative supplement is calcium citrate, which, even though it contains 21% elemental calcium, it is less dependent on gastric pH for proper absorption.

Why is ergocalciferol prescribed?

If ergocalciferol is less potent and has a shorter duration of effect, why is it used? The most likely reason is due to dosage formulations. Unlike cholecalciferol, which is typically only available as a maximum dose of 5,000 units per capsule or tablet, ergocalciferol is available as a monster 50,000 unit dose. This larger dose may be seen as more convenient for patients or healthcare providers who want to provide supplementation on a weekly or monthly basis. If needed, see: http://clincalc.com/blog/2015/07/vitamin-d2-ergocalciferol-vs-d3-cholecalciferol/

Why is taking furosemide considered a risk factor for osteoporosis?

Inc. renal elimination of Calcium

What should you recommend to help with constipation due to calcium supplements?

Magnesium. With enough magnesium, your colon walls will relax helping you pass stool along. Additionally, magnesium attracts water, meaning more water gets to your colon and softens your stool. If needed, see: https://www.algaecal.com/expert-insights/which-calcium-causes-constipation/

Calcitonin dosage forms

Nasal spray Subcutaneous injection

Zoledronic acid dosing frequency

Only IV formulation Every year for treatment; every two years for prevention.

Alendronate dosing frequency

Oral: 5 mg daily or 35 mg weekly

Ibandronate dosing

Oral: daily or monthly Available as IV: every 3 months.

Risedronate dosing

Oral: daily, weekly, monthly 35 mg dose available as immediate and extended-release.

Give example of hormonal antiresorptive agents used in treatment of osteoporosis.

Raloxifene and estrogen.

Zoledronic acid brand name

Reclast

Denosumab dosing frequency

SQ q 6 months.

Antiresorptive agents are indicated for the prevention of osteoporosis. (T or F).

T.

Counceling for biphosphonate products in general (e.g. w/ or w/o food?, other considerations?)

Take on an empty stomach, prior to breakfast with at least 8 oz of water. Depending on the product, the patient should remain upright for at least 30 to at least 60 minutes. Delayed-released risedronate can be taken 30 minutes after breakfast.

Calcium carbonate (w/ food or w/o)

Taken with food to increase calcium absorption. Food promotes more acid secretion which is believed to be important for proper calcium absorption.

Reserved for patients with severe osteoporosis (T-score below −3) and history of fractures.

Teriparatide

Use if the individual has failed other agents.

Teriparatide (b/c can cause osteosarcoma: most common type of bone cancer (although rare)

Teriparatide MOA

This agent stimulates the number and function of osteoblasts (in contrast to other agents which primarily inhibit the activity/function of osteoclasts)

Compare Vitamin D3 vs D2 in terms of sources for each.

Vitamin D3 (cholecalciferol) is produced by the human body in response to sunlight and is also available through dietary sources, such as fish. In contrast, vitamin D2 (ergocalciferol) is not produced in the human body, but is created by exposing certain plant-derived materials to ultraviolet light.

Vitamin D supplements to recommend to patients

Vitamin D3 - available over the counter Vitamin D2 available only as prescription. Products are available as cholecalciferol (vitamin D3); ergocalciferol (vitamin D2) is reserved for vitamin D insufficiency or deficiency as a prescription product. Insufficiency or deficiency can be determined by the measurement of a serum 25-hydroxy vitamin D level; the desired level is 30 ng/mL or more. Sunlight exposure (at least 15 minutes) can increase vitamin D production, but aging and sunscreens decrease or block endogenous vitamin D production.

Correct ______________ before administration of Denosumab - why?

hypocalcemia; one of its adverse effects is hypocalcemia - hence need to administer vitamin D and Calcium as necessary.

Calcitonin MOA

inhibits osteoclastic bone resorption

Teriparatide is a recombinant human ________________________ hormone

parathyroid -> hence it also increases calcium absorption in the gastrointestinal tract and reabsorption of calcium in the kidneys. Teriparatide is available as a prefilled device with 28 doses; the device should be kept in the refrigerator. A patient can self-administer the dose into the thigh or abdominal wall. A patient should be encouraged to sit down for a few minutes as it can cause orthostatic hypotension.

Contraindication to biphosphonates ->

renal insufficiency allergic reaction to biphosphonates (duh!)

Patient taking a glucocorticoid (e.g. prednisone) for longer than 3 months should be encouraged to incorporate

1) nonpharmacologic recommendations to prevent osteoporosis. 2) Alendronate and risedronate can be prescribed for a patient taking prednisone 5 mg or more for 3 months or longer. 3) Zoledronic acid and teriparatide may also be considered as alternatives to the oral bisphosphonates. see this (under pathyphys section) for explanation of mechanism: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383483/

Recommended daily intake of vitamin D for 51-70 y (men) as a measure to prevent osteoporosis.

600 units

Recommended daily intake of vitamin D for 51-70 y (women) as a measure to prevent osteoporosis.

600 units (same as men 51-70 y.o)

Recommended daily intake of vitamin D for >70 y.0 (men) as a measure to prevent osteoporosis.

800 units

Recommended daily intake of vitamin D for >70 y.0 (women) as a measure to prevent osteoporosis.

800 units (same as men > 70 y.o)

Risedronate brand name

Actonel, Atelvia (delayed-release product)

Why need to stand/sit up right for at least 30 minutes after taking Fosamax and why take it with a lot of water (8 oz.)

Alendronate (Fosamax) can cause damage to the esophagus (food pipe) - If you lie down the medication might come back up into the esophagus, so that is why you should not lie down.. More water will help wash the medication down into the stomach and away from the esophagus see https://www.ncbi.nlm.nih.gov/pubmed/10619269 - abstract about how alendronate causes esphageal damage. *Note - same instructions apply to other biphosphonates*

Examples of Biphosphonates

Alendronate, ibandronate, risedronate and zoledronic acid

SP is a 60-year-old postmenopausal obese woman with a history of DVTs. She has a family history of osteoporosis and breast cancer and inquires about the use of raloxifene, because she heard that it might prevent osteoporosis and protect against breast cancer. Which one of the following is a correct statement? A) She does not have an indication for raloxifene due to her menopausal status. B) She has a contraindication due to her history of DVT. C) Her family history of breast cancer precludes use of raloxifene. D) Raloxifene is not indicated for her age group. E) Raloxifene is an appropriate agent for MW.

B C is wrong b/c raloxifene is actually indicated for breast cancer patients who are at risk for osteoporosis.

TB is a 78-year-old man with a history of vertebral compression fractures, hypertension, osteoarthritis, and depression. Spinal kyphosis is noted on physical examination. Laboratory results show normal testosterone and vitamin D levels. DXA results include aT-score of -2.2 in the left hip and -2.9 in the lumbar spine. His physician would like to initiate treatment for osteoporosis. Which initial therapy is recommended for this patient? A) Testosterone 200 mg intramuscularly every 4 weeks B) Alendronate 70 mg orally once weekly 30 minutes before breakfast C) Calcitonin salmon nasal spray one spray daily in alternating nostrils D) Teriparatide 20 mcg subcutaneously daily E) Ibandronate 150 mg by mouth every month

B. Tesosterone is not indicated for osteoprosis period.

Which of these do we use as primary agent for treatment/prevention of osteoporosis: Biphosphonates or antiresportive hormonal therapies such as Raloxifene?

Biphosphonates. Hormonal therapies such as Raloxifene will be used as alternative agents if bisphosphonates are ineffetive or intolerable b/c they have cardiovascular and thromboembolic risks.

First-line therapy for the treatment of osteoporosis among men.

Bisphosphonates

Which osteoporosis drug is correctly matched with its contraindication? A) Zoledronic acid—previous thromboembolism B) Calcitonin—bone pain C) Denosumab—uncorrected hypocalcemia D) Raloxifene—osteosarcoma E) Teriparatide—uncorrected hypocalcemia

C.

CC is a 57-year-old woman with osteoarthritis, GERD, migraines, and hypertension who takes omeprazole daily, lisinopril daily, ibuprofen TID as needed for pain, and sumatriptan as needed for migraines. Which condition or medication may increase her risk of osteoporosis? A) Ibuprofen B) Osteoarthritis C) Omeprazole D) Sumatriptan E) Lisinopril

C. Osteoarthritis is a disease affecting the joints not really the bones and there hasn't been an established link between the two. Omeprazole decreases calcium absorption. Calcium is absorbed in its ionic form and this requires an acidic medium.

Available as an intranasal agent and should be stored in the refrigerator.

Calcitonin - Prior to use, the bottle should be at room temperature, assembled and primed. The dose should be sprayed straight up into the nostril.

This formulation of calcium contains the most elemental calcium (40%) and has a variety of formulations (tablet, chewable, liquid).

Calcium carbonate

Why do Calciuim supplements cause constipation?

Calcium contracts muscles. If you're getting too much calcium the muscle walls of your colon contract, making it harder to pass stool. The longer your stool sits in the colon, the more water is pulled out of it. This makes the stool dense and hard, making it significantly harder to pass and likely painful. If needed, see: https://www.algaecal.com/expert-insights/which-calcium-causes-constipation/

Compare Vitamin D3 vs D2 in terms of their potencies.

Cholecalciferol (vitamin D3) is 1.7 to 3 times more potent and has a longer-lasting effect than ergocalciferol in increasing serum 25-hydroxyvitamin D levels, the active form of vitamin D in humans. The difference in duration of effect and potency are well demonstrated in a study by Armas et al

AK is a 66-year-old woman who was recently prescribed teriparatide. Which is an important counseling point for this medication? A) Injection pens should be kept frozen until they are ready to be used. B) Each injection pen should last 90 days. C) This medication should be administered once a month. D) Contact your doctor right away if you have bone pain. E) This medication can only be used for a maximum of 5 years.

D.

RW is a 45-year-old African-American woman with an 18 pack-year smoking history who quit 10 years ago and has a BMI of 32 kg/m2. She is currently on a 1-week prednisone taper for an asthma exacerbation and takes lisinopril 20 mg daily for hypertension. Which characteristic is associated with an increased risk of developing osteoporosis? A) African American ethnicity B) Presence of hypertension C) Present systemic oral glucocorticoid therapy D) Female sex E) BMI greater than 30 kg/m2

D.

TD is a 68-year-old man with several risk factors for osteoporosis, including current cigarette smoking, alcohol consumption of three to five drinks per day, low body weight, and physical inactivity. Laboratory test results showed 25-hydroxyvitamin D level of 18 ng/mL (45 nmol/L). What recommendation can be made for TD to decrease his osteoporosis risk? A) Increase dietary intake of fortified milk, egg yolks, and salt-water fish B) Increase sun exposure + vitamin D3 800 IU daily C) Calcium citrate + D3 200 IU twice daily + multivitamin (vitamin D3 400 IU) daily D) Ergocalciferol 50,000 IU once weekly for 8 weeks; then cholecalciferol 2000 IU daily E) Ergocalciferol 50,000 IU once weekly indefinitely

D.

Which patient is a candidate for screening BMD measurement? A) 55-year-old woman with osteoarthritis B) 48-year-old woman with wrist fracture secondary to motor vehicle crash C) 69-year-old man with 40 pack-year history of smoking, quit 5 years ago D) 68-year-old woman with 2-cm height loss from adulthood E) 25-year-old woman who received a 10-day course of steroids for asthma

D.

Why need calcium in patients with osteoporosis?

Decrease bone turnover rate

An alternative agent for treatment of osteoporosis, especially among patients who cannot tolerate or have a contraindication to bisphosphonates (eg, renal insufficiency).

Denosumab

MOA - RANK ligand inhibitor

Denosumab

You are a pharmacist involved in bone density screening during a health fair in your community. Several patients present to your booth for a peripheral bone density measurement. Based on the following descriptions and recommendations from the National Osteoporosis Foundation, who should be referred to a health care provider for follow-up and evaluation of bone mineral density by central DXA? A) 71-year-old man with low bone mineral density B) 66-year-old woman with low calcium intake and nicotine dependence C) 53-year-old active African-American man receiving chronic glucocorticoid therapy D) 58-year-old woman with a FRAX 10-year probability of hip fracture of 3.2% E) All of these patients meet criteria for screening by central DXA.

E.

CM is a 62-year-old woman who recently started bisphosphonate therapy for osteoporosis. Due to a history of dry mouth, the patient is experiencing difficulty swallowing her ibandronate tablets. What the best recommendation for CM? A) Take ibandronate with the first meal of the day. B) Take ibandronate with a full glass of milk. C) Crush the ibandronate tablet and mix it with a small amount of pudding or applesauce and take it. D) Dissolve ibandronate in a full glass of water and drink it. E) Consider switching to an IV bisphosphonate.

E. NEVER take ibandronate with food b/c it signficantly decreases its abosrption. Same goes with drinks like milk, coffee or tea. D is wrong b/c ibandronate doesn't come in effervescent tablet - that would be true if we were talking about alendronate.

Why not take Alendronate with food?

Food *markedly* inhibits oral absorption. see: https://www.ncbi.nlm.nih.gov/pubmed/10384857 if needed *Note - same instructions apply to other biphosphonates except for delayed-release product of risedronate.

Alendronate brand name:

Fosamax

Why is taking aromatase inhibitors considered a risk facor for osteoporosis?

Inhibit the enzyme that converts testosterone to estrogen. Decrease estrogen concentrations lead to increase osteoclast activity.

Vitamin D is important in osteoporosis prevention and treatment. Why?

It increases calcium absorption.

Denosumab mechanism of action

Mimics osteoprotegerin preventing the maturation and activity of osteoclasts. Targets a ligand known as RANKL (*r*eceptor *a*ctivator of *n*uclear factor-*κ*B *l*igand) protein in osteoclasts stopping bone resorption; prevents fractures

A non-pharmacological method to recommend to increase endogenous vitamin D production

Sunlight exposure (at least 15 minutes) can increase vitamin D production. Note aging and sunscreens may decrease or block endogenous vitamin D production

How do PPI cause osteoporosis?

The most widely assumed mechanism is that long-term PPI use leads to decreased intestinal absorption of calcium resulting in negative calcium balance -> Calcium is though to be absorbed in ionized form primarily in the upper small intestine and the ionization is facilitated by an acidic medium to release calcium from its salt form

Sources of Vitamin D to recommened for patient with osteoporosis?

There are several dietary sources of vitamin D, such as fortified milk, orange juice, or cereals. However, it is difficult for a patient to have adequate vitamin D intake; therefore, supplements are generally recommended for any individual older than 50 years For meaning of fortified milk: https://healthyeating.sfgate.com/mean-milk-not-fortified-6662.html

Intravenous formulations of bisphosphonates are available for those patients who

are not able to tolerate oral bisphosphonates (eg, gastrointestinal issues) and not willing to follow the specific instructions on how to take them. -> ibandronate and zaledronic acid.

Drug holiday has been suggested for

biphosphonates. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about adverse effects related to long-term use. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a 'drug holiday.' There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707342/#section3-1759720X13477714title