Vitamin D:A Review of Guideline Recommendations and Fall Risk Association in Older Adults

MOLLY A. HAFERMAN, PHARMD, RPHPGY1 PHARMACY RESIDENTMAYO CLINIC HEALTH SYSTEM EAU CLAIRE, WI

DisclosuresThe speaker has no actual or potential conflicts of interest in relation to this presentation

ObjectivesDetermine the patient population who benefits most from vitamin D replacement therapy

Classify a patient’s vitamin D status based on his/her vitamin D concentration

Select appropriate therapy for vitamin D deficient patients

Falls and the Older Adult

Falls and Older AdultsLeading cause of injuries and death in patients ≥65 years old

• 1 in 3 Americans aged 65+ fall every year

Every 13 seconds and older adult is seen in the emergency department (ED) for a fall-related injury

2013 statistics• 2.5 million were treated in the ED for nonfatal falls• 734,000+ were hospitalized

https://www.ncoa.org/healthy-aging/falls-prevention/Karani MV, Haddad Y, Lee R. The Role of Pharmacists in Preventing Falls among America's Older Adults. Front Public Health. 2016;4:250.

https://www.cdc.gov/homeandrecreationalsafety/falls/adultfalls.html

A Growing Problem

https://www.cdc.gov/steadi/pdf/STEADI_ClinicianFactSheet-a.pdf

Implications of Falls

Increased medical costs

Functional decline/

mobility issuesReduction in quality of life

Serious injuries

Loss of independence Fear of falling

https://www.ncoa.org/wp-content/uploads/FallsActionPlan_2015-FINAL.pdfhttps://www.cdc.gov/homeandrecreationalsafety/falls/adultfalls.html

Fact or Myth?Falls are a normal part of aging

MYTH

Modifiable Risk-FactorsGait and balance problemsVision impairmentFoot conditionsMedications (polypharmacy)Vitamin D deficiency

Pharmacists’ Role in Fall Prevention

https://www.cdc.gov/steadi/https://www.ncoa.org/resources/2015-falls-free-national-falls-prevention-action-plan/

Algorithm for Fall Risk Assessment & Interventions

https://www.cdc.gov/steadi/pdf/Algorithm_2015-09-print.pdf

Vitamin D Status and Recommendations

Vitamin D• Fat-soluble vitamin

• Hormonal regulation of:• Calcium phosphate homeostasis • Mineral bone metabolism

Halfon M, Phan O, Teta D. Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty. Biomed Res Int. 2015;2015:953241.

UpToDate®

Vitamin D2(ergocalciferol)

• Found in some plants• Produced commercially by

irradiation of yeast• Used for fortification• Prescription formulation

Vitamin D3(cholecalciferol)

• Produced in the skin following UV radiation from sunlight

• Can be obtained from the diet

• Over-the-counter (OTC)

Alldredge BK, Corelli RL, Ernst ME. Koda-Kimble and Young's Applied Therapeutics, The Clinical Use of Drugs. Lippincott Williams & Wilkins; 2012.

↑ Vitamin D

↑Bone calcium mobilization

↑ Intestine calcium absorption

↓Parathyroid gland (PTH) secretion

Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1):50-60.

Vitamin D Status Classification

25(OH) Vitamin D Concentration

Vitamin D Status Classification

< 10 ng/mL Deficient

11-29 ng/mL Insufficient

≥ 30 ng/mL Optimal

Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1):50-60.UpToDate®

SymptomsToxicity DeficiencyHypercalcemiaMental status changesNausea/vomitingWeaknessKidney stones (excess renal calcium excretion)

Muscle weaknessBone painWeaknessFrequent fracturesNeuropathyArthropathies

UpToDate®

Causes of Vitamin D Deficiency↓ intake

↓ absorption

↓ sun exposure

↑ hepatic catabolism

↓ endogenous synthesis

Who is at Risk for Vitamin D Deficiency?

Dark skinnedObese (Body mass index (BMI) >30 kg/m2)HospitalizedMalabsorption syndromes

• Inflammatory bowel disease (IBS)• Celiac disease

Use of medications that accelerate vitamin D metabolism• Cytochrome P450 inducers (ex: phenytoin, phenobarbital)

Limited sun exposurePregnant

Relationship of Vitamin D and Fall RiskDirect effects on muscle cells

Halfon M, Phan O, Teta D. Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty. Biomed Res Int. 2015;2015:953241

Better gait and balance

Improved muscular function

Improved contraction

Promotion of muscle cell proliferation

American Geriatrics Society (AGS) Recommendations

Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014;62(1):147-52.

1000 IU/day

Achieves recommended

levels in only 1/2 of older adults

4000 IU/day

Ensures 92% of the population achieve

serum 25(OH)D levels of 30 ng/mL

Support for Recommendations

Bischoff-Ferrari et al.

Vitamin D 700-1000 IU daily

↓ fall risk =19%

RR=0.8195% CI 0.71-0.92

Vitamin D 200-600 IU daily

No reduction in fall risk

RR=1.095% CI 0.89-1.35

Bischoff-ferrari HA, Shao A, Dawson-hughes B, Hathcock J, Giovannucci E, Willett WC. Benefit-risk assessment of vitamin D supplementation. Osteoporos Int. 2010;21(7):1121-32.

Support for RecommendationsFaulkner et al.

• Higher serum 25(OH)D concentration associated with lower fall rates (p=0.039)

Faulkner KA, Cauley JA, Zmuda JM, et al. Higher 1,25‐dihydroxyvitamin D3 concentrations associated with lower fall rates in older community‐dwelling women. Osteoporos Int. 2006;17(9):1318‐28.

Why did AGS choose 4,000 IU for their recommendation?Likely lower adherence than in the trials

Studies demonstrating fall and fracture reduction saw serum 25(OH)D levels >26 ng/mL

• The recommendation of >30 ng/mL is a conservative estimate

Recommended dose will not push patients into toxic levels

Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014;62(1):147-52.

Vitamin D Sources

Conflicting RecommendationsInstitution RecommendationInstitute of Medicine (IOM) Daily dietary allowance:

≤70 years old: 600 IU daily>70 years old: 800 IU daily

United States Preventative Services Task Force

≥ 65 years old, community dwellingadults: exercise or physical therapy and vitamin D supplementation if at increased risk for falls

American Geriatrics Society (AGS) Total daily intake from all sources of 4000 IU ensures 92% of older adults will have serum vitamin D levels of 30ng/mL

http://www.pharmacytimes.com/publications/issue/2015/september2015/vitamin-d-supplementation-and-fall-prevention-in-the-elderly. Accessed April 13, 2017.

Medscape

Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014;62(1):147-52.

High Dose Vitamin D: Helpful or Harmful?

Vital D Study

• Vitamin D 500,000 units single dose vs. placebo given each year for 3-5 years in autumn/winter

• Single-center, double-blind, randomized placebo-control study

• 2317 study participants (all women)• Victoria, Australia• Study participants followed for 12 months post-last

dose

Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-22.

High Dose Vitamin D: Helpful or Harmful?

More falls seen in vitamin D group than in the placebo group

Incidence Rate Ratio: 1.16 (95% CI 1.05-1.28); p=0.003

Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-22.

High Dose Vitamin D: Helpful or Harmful?

A Meta-Analysis of High Dose, Intermittent Vitamin D Supplementation Among Older Adults• Nine trials included in analysis• 22,012 patients (Vitamin D=10,980;

control=11,062)• RR:1.02 • 95% CI: (0.96-1.08); p=0.52• No benefit seen in fracture or fall reduction

Zheng YT, Cui QQ, Hong YM, Yao WG. A meta-analysis of high dose, intermittent vitamin D supplementation among older adults. PLoS ONE. 2015;10(1):e0115850.

Which to choose? Vitamin D2 or Vitamin D3• Different pharmacokinetic profiles

• 25(OH)D levels more consistent with vitamin D3• Higher serum concentrations achieved• Longer half-life

• Vitamin D2 can lead to fluctuations of serum 25(OH)D concentrations

When to monitor?• Routine monitoring is not required

• If physicians choose to monitor, recommend to check levels after 4 months of treatment

• Can consider monitoring in the high-risk groups

Patient Case & Discussion

Which of the following patients would benefit most from vitamin D supplementation?a) 30 year old Caucasian with Celiac Disease

b) Obese, 75 year old African American living in a Wisconsin nursing home

c) 82 year old retired farmer living in Arizona

d) 54 year old epileptic taking phenytoin for seizure prophylaxis

Patient Case• Mrs. White (81 year old) Caucasian woman

who resides at an assisted living facility

• Fell 1 week ago getting out of the shower. Son states his mother has “had too many falls to count” within the last year

• Reports falls happen during the day and during the night

• Vitamin D level = 12 ng/mL

Case adapted from: https://www.cdc.gov/stedi/pdf/STEADI_Case Study3_V3‐a.pdf

PMHType 2 DM

Congestive heart failure

Osteoarthritis

Osteopenia

CKD Stage 3

Macular degeneration

GERD

Insulin lispro 3 units subQ with meals

Insulin glargine 20 units subQat bedtime

Lisinopril 20 mg daily

Metoprolol ER 200 mg daily

Spironolactone 12.5 mg daily

Furosemide 20 mg daily

Digoxin 125 mcg daily

Fluoxetine 40 mg daily

Clonazepam 0.5 mg at bedtime PRN sleep

Medications

True or FalseBased on Mrs. White’s vitamin D levels, she is considered vitamin D deficient according to the AGS

25(OH) Vitamin D Concentration

Vitamin D Status Classification

< 10 ng/mL Deficient

11-29 ng/mL Insufficient

≥ 30 ng/mL Optimal

Select the best treatment option for Mrs. White as recommended by the AGS:

a) No vitamin D supplementation needed at this time

b) 1000 IU vitamin D supplement once daily

c) 800 IU vitamin D supplement once daily

d) 4000 IU vitamin D daily from all sources

SummaryFalls are the leading cause of injuries and death in patients ≥65 years old

Adequate vitamin D supplementation can help reduce fall risk in older patients

Target 25(OH)D levels ≥ 30 ng/mL are optimal• 1000 IU/day will achieve recommended vitamin D levels in

only half of older adults• Average daily intake of 4000 IU from all sources will

ensure 92% of the population achieve this

References1. https://www.ncoa.org/healthy-aging/falls-prevention/

2. Karani MV, Haddad Y, Lee R. The Role of Pharmacists in Preventing Falls among America's Older Adults. Front Public Health. 2016;4:250.

3. https://www.cdc.gov/homeandrecreationalsafety/falls/adultfalls.html

4. https://www.ncoa.org/wp-content/uploads/FallsActionPlan_2015-FINAL.pdf

5. https://www.cdc.gov/homeandrecreationalsafety/falls/adultfalls.html

6. https://www.cdc.gov/steadi/

7. Halfon M, Phan O, Teta D. Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty. Biomed Res Int. 2015;2015:953241.

8. Alldredge BK, Corelli RL, Ernst ME. Koda-Kimble and Young's Applied Therapeutics, The Clinical Use of Drugs. Lippincott Williams & Wilkins; 2012.

9. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1):50-60.

10. Zheng YT, Cui QQ, Hong YM, Yao WG. A meta-analysis of high dose, intermittent vitamin D supplementation among older adults. PLoS ONE. 2015;10(1):e0115850.

11. http://www.pharmacytimes.com/publications/issue/2015/september2015/vitamin-d-supplementation-and-fall-prevention-in-the-elderly. Accessed April 13, 2017.

12. http://www.medscape.org/viewarticle/818569. Accessed April 12, 2017.

13. Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014;62(1):147-52.

14. Holick M et al. Evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:1911-1930.

15. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-22.

16. Bischoff-ferrari HA, Shao A, Dawson-hughes B, Hathcock J, Giovannucci E, Willett WC. Benefit-risk assessment of vitamin D supplementation. Osteoporos Int. 2010;21(7):1121-32.

17. Faulkner KA, Cauley JA, Zmuda JM, et al. Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates in older community-dwelling women. Osteoporos Int. 2006;17(9):1318-28.

References

QUESTIONS

Vitamin D:A Review of Guideline Recommendations and Fall Risk Association in Older Adults

MOLLY A. HAFERMAN, PHARMD, RPHPGY1 PHARMACY RESIDENTMAYO CLINIC HEALTH SYSTEM EAU CLAIRE, WI