Update in Vitamin D Deficiency Marc Cornier, MD Division of Endocrinology, Metabolism and Diabetes University of Colorado Denver Denver Health Medical Cener [email protected]

Case: Assessment • • • • • • •

Type 2 Diabetes Hypertension Metabolic Dyslipidemia Obesity Depression Osteopenia Vitamin D Deficiency?

Metabolic Syndrome

Vitamin D Metabolism 7-dehydrocholesterol

Diet/Supplements

UV light skin Cholecalciferol (Vitamin D3)

Ergocalciferol (Vitamin D2) Liver

Calcidiol (25-hydroxy Vitamin D) PTH

Kidney Calcitriol (1,25-dihydroxy Vitamin D) _ Intestinal Ca Absorption

Bone Resorption

_ Renal Ca and Phos Excretion

Vitamin D Deficiency Disorders • Primary or Congential Vitamin D Deficiency • Acquired Vitamin D Deficiency: – – – – – – –

Poor intake or Malabsorption Inadequate sunlight Liver disease Renal disease Hypoparathyroidism Obesity Medications

Factors Affecting Cutaneous Vitamin D Production • Skin Pigmentation – Darker skin associated with lower vitamin D levels (higher incidence of vitamin D deficiency) and less conversion in response to sun exposure.

• Age • Sunscreen use • Season of the year and time of day

Factors Affecting Vitamin D Production: Sunscreen

Serum Vitamin D (nmol/L)

Sunscreen with an SPF of 8 inhibits 97.5% of vitamin D production

100 90 80 70 60 50 40 30 20 10 0

No Sunscreen

Sunscreen

-1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Days Following Light Exposure Matsuoka LY, et al. JCEM. 64:1165–1168, 1987.

Boston Edmonton Bergen

6

200 25(OH) Vit D (nmol/L)

5

Mean 122 (50 ng/ml)

250

7

4 3 2 1

Mean 74 (30 ng/ml)

150 100 50

De

c

0

Ja n Fe b M ar Ap r M ay Ju n Ju l Au g Se p O ct No v

Pre Vitamin D3 formation, %

Seasonal Variation of Vitamin D levels

Chen TC: In Vitamin D—Physiology, Molecular Biology, and Clinical Applications. Edited by Holick MF. Totowa, NJ: 17, 1999.

Summer

Winter

What is Vitamin D Deficiency? • Definition has changed of the last 20 years • No consensus on optimal levels >20? >30? >40?

• There is consensus that levels < 15 ng/dl represent true deficiency • Severe deficiency (Levels < 8 ng/dl) is associated with rickets in children and osteomalacia in adults • Should probably be “worked up”

• Levels of < 20-30 are considered “subclinical” deficiency or “insufficiency” • Even mild deficiency is associated with bone loss

• Broad-based screening, however, is not recommended should individualize

Vitamin D Deficiency Secondary Hyperparathyroidism

80 70 60

Normal Range

Serum PTH Level

90

50 40 30 20 10 0 5

10

15

20

25

30

35

Serum 25 OH Vitamin D Level (ng/ml) Thomas M, N Engl J Med 1998; 338:777

The Majority of American Women Are Not Receiving Adequate Intake of Vitamin D Percent of Women With Inadequate Intake of Vitamin D (Diet + Supplement)

> 50 yr):, over 70% of women 51-70 years did not meet adequate guidelines for vitamin D intake based on diet and supplements (400 IU).

• Nearly 90% of women older than 70 years did not meet guidelines (600 IU).

Percent Not Consuming Adequate Intake (AI) Vitamin D

• NHANES III (3,444 women

100 90 80 70 60 50 40 30 20 10 0

Women 51–70 y

Women >70 y

NHANES = National Health and Nutrition Examination Survey. Moore C et al. J Am Diet Assoc. 2004;104:980–983.

Prevalence, % (± 95% CI)

Low Vitamin D Levels Are Prevalent in Postmenopausal North American Women Receiving Therapy Indicated For Osteoporosis 60

52.0

50 35.5

40 30 18.2

20 10 0

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