To D Or Not To D, That
Is The Question.
Rick Padilla, MD
Denver Health
March 10, 2009
Case
Mrs. G. is a 68 yo HF with hx of metabolic
syndrome and seizure disorder who comes in
for routine follow up. She has no acute
complaints. Her last seizure was 3 months
ago and she has 3-4 seizures per year. Her
rx are glucovance 5/500 mg daily, crestor 5
mg qhs, zestoretic 20/25 mg daily, aspirin 81
mg daily, OTC calcium 2 tabs per day and
dilantin 300 mg qhs. BP 124/74, P 72, RR
16, BMI 30.2 Physical exam is normal.
Case continued
Pertinent studies, HgBA1C = 6.9, LDL =
88, creat cl = 60, spot UA = moderate
microalbumin. No recent dilantin level.
A Dexa scan done 1 year ago reveals
normal BMD with a T score of 0.8.
Should you order a 25 OH vitamin D
level on this patient?
Vitamin D Basics
Rule of thumb
For
1 g of D3 or D2 = 40 IU
Prevalence of Vitamin D
Deficiency
In several studies, 40 to 100% of U.S. and
European elderly men and women still living
in the community are vitamin D deficient
More than 50% of postmenopausal women
taking rx for osteoporosis are vitamin D
deficient (Holick et al. J Clin Endocrinol Metab
2005)
45/80 (56.2%) of geriatric patients in a
UCDSOM study of vit. D education
intervention study were vitamin D deficient.
(VandeGriend et al. J Am Pharm Assoc 2008)
nmol/L
25-OH-D levels
(nmol/L)
decrease with
age, % body fat
and BMI
nmol/L
D3 D2 1,25-di(OH)-D3
D3 is made in the skin* (or ingested in
supplements) not biologically active
Cholecalciferol
Ergocalciferol
**From ergosterol
Sources of Vitamin D
Exposure to sunlight
Dietary Sources
Dietary Supplements
Exposure to Sunlight
5-10 minutes of direct exposure to the arms and
legs = 3000 IU of vitamin D3
In a study of 69 healthy subjects age 18-29 in
Boston, 36% had 25 OH vit D level < 20 ng/ml at
the end of winter. The prevalence decreased to
4% by the end of summer. (Tangpricha Am J Med
2002)
Multiple studies show vitamin D def. common in
sunny areas when most of the skin is shielded from
the sun (Saudi Arabia, United Arab Emirates,
Turkey, India and Lebanon)
Sources of Vitamin D
1,25 OH Vitamin D
Effects
Increased calcium absorption in the gut
Increased PTH mediated bone
resorption
Decreased renal calcium and
phosphorus excretion
Decreased PTH secretion
Increased bone calcification
PTH Effects
Increases tubular reabsorption of calcium and
stimulates the kidney to produce 1,25 OH
vitamin D
Activates osteoblasts , which then stimulates
the activation of osteoclasts, which dissolve
mineralized collagen matrix in the bone,
causing osteopenia and osteoporosis and
increasing the risk of fracture.
Causes phosphaturia. A low Ca-Phos
product leads to decreased mineralization of
the collagen matrix= rickets in kids and
osteomalacia in adults
Osteomalacia
Softening of the bone due to impaired
mineralization due to low Ca-Phos product.
Symptoms include isolated or generalized
bone pain, muscular weakness, and weight
loss
93% of 150 persons 10 to 65 year old seen in
an ED in Minnesota with muscle aches and
bone pain were deficient (< 20 ng/ml) in
vitamin D and 28% had severe deficiency (< 8
ng/ml) (Plotnikoff, Mayo Clin Proc 2003)
Mechanisms of Vitamin
D Deficiency
Reduced skin synthesis
- Sunscreen use (SPF 15 reduces vitamin D3
synthesis by 99%)
- Skin pigmentation
- Aging (reduction of 7 dehydrocholesterol
reduces vitamin D3 synthesis by 75% in a 70
year old)
- Season, latitude and time of day
-Patients with skin grafts for burns
Mechanisms of Vitamin D
Deficiency Continued
Impaired availability of vitamin D due to inadequate
dietary intake, malabsorptive disorders and obesity
(sequestration of vitamin D in body fat)
Impaired hydroxylation by the liver due to liver
disease
Increased hepatic catabolism due to medications
Impaired renal production of 1,25 OH vit. D in
stage 4 and 5 CKD
Renal loss of vit. D and vit. D binding proteins in
nephrotic syndrome
Phenytoin
Phenobarbital
Carbamazepine
Isoniazid
Theophylline
Rifampin
Glucocorticoids
HAART
Number of First Nonvertebral Fractures among All Subjects, According to Skeletal Site
FIGURE 2. Relative risks (RRs; {square}) of hip fracture (A) and nonvertebral fracture (B)
between subjects who took vitamin D and control subjects
5.4
yr follow-up
120 developed first CV event
Wang TJ, et al. Circulation 2008;117:503-511.
Adj for
*covar.
Adj. for
*covar., CRP
25-OH-D >15
1.00
1.00
1.00
10 to <15
2.07
1.93
2.07
(1.19-3.61)
(1.09-3.42)
(1.16-3.69)
3.19
2.51
2.43
(1.70-5.99)
(1.30-4.82)
(1.23-4.80)
25-OH-D >15
1.00
1.00
1.00
10 to <15
1.45
1.06
1.05
(0.74-2.82)
(0.53-2.13)
(0.52-2.13)
1.66
1.00
1.08
(0.35-2.85)
(0.37-3.16)
No HTN
Hypertension
ng/mL
<10
<10
(0.64-4.28)
Compared with
25-OH-D >30
ng/mL
<15
ng/mL
15-22.5
ng/mL
22.6-29.9
ng/mL
RR of MI after
adjustment*
2.09
1.43
1.60
(1.24-3.54)
(0.96-2.13)
(1.10-2.32)
*FHx MI, BMI, EtOH, activity, DM, HTN, ethnicity, region, marine -3 intake, LDL, HDL, TG
Giovannucci E, et al. Arch Intern Med 2008;168(11):1174-1180.
Final
Ca only
Vit. D + Ca
Ca only
Vit. D + Ca
24.6
25.7
44.4
64.8
(17.8 ng/mL)
(25.9 ng/mL)
PTH (pmol/L)
6.1
6.1
5.3
4.6
SBP (mmHg)
140.6
144.1
134.9
131.0
DBP (mmHg)
82.6
84.7
75.7
77.5
HR (mmHg)
74.1
75.4
73.9
71.3
Vitamin
D and
In 10,366 children
in Finland
givenDiabetes
2000 IU of vitamin D3
per day during their first year of life and then followed for 31
years, the risk of type 1 DM was reduced by 80%. In
subset analysis, among children with vitamin D deficiency,
the risk was increased by 200%. (Hyponen, Lancet 2001)
Combined daily intake of 1200 mg of calcium and 800 IU of
vitamin D lowered the risk of type 2 diabetes by 33 %
compared to daily intake of less than 600 mg calcium and
less than 400 IU of vitamin D. (Pittas, Diabetes Care 2006)
Proposed mechanism: The 1,25 OH vitamin D produced in
the kidney enters the circulation and stimulates insulin
secretion in the islet cells of the pancreas
Restricted cubic spline showing the fully adjusted associations between serum 25hydroxyvitamin D (25[OH]D) levels and all-cause mortality in 13 331 participants of the Third
National Health and Nutrition Examination Survey
Participants with recent upper respiratory tract infection (URTI) stratified by serum 25hydroxyvitamin D level (to convert to nanomoles per liter, multiply by 2.496) and season
Vitamin D Deficiency
and Other Conditions
Linked to increased incidence of :
Schizophrenia
Depression
Reactive Airway Disease
Elderly
Home bound or institutionalized patients
Patients with known or suspected malabsorption
Patients with osteoporosis or osteopenia
CKD patients
Chronic liver disease patients
Patients with nonspecific musculoskeletal pain
Patients on medications that induce P-450
enzyme activity
Obese
Vitamin D Intoxication
Common symptoms:anorexia, nausea
and vomiting, polyuria, polydipsia,
weakness and pruritus
Lab abnormalities: AKI, hypercalcemia
and hyperphosphatemia
Treatment: stop vitamin D, low calcium
diet, acidify the urine and steroids
Mrs. G.
Should you order a 25 OH vitamin D
level on this patient?
Mrs. G.
Age 68
BMI 30.2
DEXA with normal BMD (T score 0.8)
On OTC calcium
On dilantin
Mrs. G.
25 OH vitamin D level = 18 ng/ml
Was started on ergocalciferol 50,000 IU
per week x 8 weeks
Repeat 25 OH vitamin D level after
treatment = 35 ng/ml
Now on maintenance therapy of
ergocalciferol 50,000 IU every 4 weeks