malabsorption; accelerated catabolism from certain medications; and, in infants, the minimal amount of vitamin D found in breast milk. In children, vitamin D deficiency can result in rickets, which presents as bowing of the legs; in adults, it results in osteomalacia, which presents as a poorly mineralized skeletal matrix. See the image below.
Findings in patients with rickets.
Essential update: Low vitamin D in moms linked to long-term health outcomes in kids
In a community-based study of 901 mother and offspring pairs, researchers found that maternal vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/L) at 18 weeks' pregnancy was associated with impaired lung development at age 6 in offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at age 20.[1, 2]
Findings suggest that vitamin D plays an active role in fetal development, particularly the development of the brain, lungs, and bones.
History
Vitamin D deficiency is often a silent disease. By definition, rickets occurs in children whose growth plates have not fused. These children are often found to have started walking late or prefer to sit down for prolonged periods. In adults, vitamin D deficiency results in osteomalacia, which presents as a poorly mineralized skeletal matrix. Adults in these cases can experience chronic muscle aches and pains.[8]
Vitamin D deficiency is the most common cause of nutritional rickets. Rare genetic forms of rickets occur because of defects in vitamin D metabolism. Vitamin D–dependent rickets type I occurs because of a defect in the renal 25-hydroxyvitamin D-1 alpha-hydroxylase that results in decreased 1,25(OH)2 D production. Vitamin D–dependent rickets type II occurs when a mutation exists in the VDR.
Physical examination
In children with a severe vitamin D deficiency, the examination may reveal bowing in the legs. In adults with a severe vitamin D deficiency, the examination can reveal periosteal bone pain. This is best detected using firm pressure on the sternal bone or tibia
Signs and symptoms
Vitamin D deficiency is often clinically silent. Manifestations are as follows:
- Children are often found to have started walking late or prefer to sit down for prolonged periods
- Adults can experience chronic muscle aches and pains
Physical findings in severe vitamin D deficiency are as follows:
- In children, bowing in the legs
- In adults, periosteal bone pain, best detected with firm pressure on the sternum or tibia
Diagnosis
Measurement of serum 25-hydroxyvitamin D (25[OH]D) is the best test to determine vitamin D status. levels of 25(OH)D are interpreted as follows[3] :
- 21-29 ng/mL (52.5-72.5 mmol/L): Vitamin D insufficiency
- < 20 ng/mL (< 50 mmol/L): Vitamin D deficiency
Although not always required for the diagnosis of vitamin D insufficiency, measurement of the serum parathyroid hormone (PTH) level may help establish the diagnosis of vitamin D insufficiency. PTH levels are often elevated in patients with vitamin D insufficiency, indicating secondary hyperparathyroidism.
Screening for vitamin D deficiency is recommended only in those individuals who are at high risk for vitamin D deficiency, including the following[4] :
- Patients with osteoporosis
- Patients with a malabsorption syndrome
- Black and Hispanic individuals
- Obese persons (body mass index >30 kg/m2)
- Patients with disorders that affect the metabolism of vitamin D and phosphate (eg, chronic kidney disease)
Diagnostic Considerations
Conditions to be considered in the differential diagnosis of vitamin D deficiency include the following:
- Lack of dietary intake
- Inadequate sunlight exposure
- Malabsorptive diseases - Celiac sprue, short bowel syndrome, cystic fibrosis
- Use of antiepileptic medications that accelerate vitamin D metabolism - Phenytoin, phenobarbital
- End-stage liver disease
Approach Considerations
The Endocrine Society, along with the Canadian Society of Endocrinology and Metabolism and the National Osteoporosis Foundation, published a clinical practice guideline in 2011 titled "Evaluation, Treatment and Prevention of Vitamin D Deficiency." The committee recommended screening of only those individuals who are at high risk for vitamin D deficiency, including patients with osteoporosis or a malabsorption syndrome, as well as black and Hispanic individuals, obese persons (BMI >30 kg/m2), and those with several other medical conditions.
The daily maintenance dose of vitamin D varies by age, but most children and adults generally require 600-2000 IU of vitamin D daily. For vitamin D-deficient children and adults, higher doses of vitamin D given either daily or weekly are recommended, followed by an increase in the daily dose of vitamin D.[4]
In a population-based study, the electronic medical records of more than 1,200,000 members of a health maintenance organization (HMO) were analyzed to determine the upper limit of vitamin D beyond which there is an increased risk of acute coronary syndrome (ACS) or mortality.[60, 61] The lowest risk of mortality and morbidity was reported in members with vitamin D levels in the 20-36 ng/mL range.[61] The hazard ratio increased not only below but also above this range, with adjusted hazard ratios of 1.88 among subjects with vitamin D levels lower than 10 ng/mL, 1.25 among those with levels of 10-20 ng/mL, and 1.13 among those with levels higher than 36 ng/mL (P < 0.05).
Management
Recommended treatment for vitamin D–deficient patients up to 1 year of age is as follows[4] :
- 2000 IU/day of vitamin D2 or D3 for 6 weeks or
- 50,000 IU of vitamin D2 or D3 once weekly for 6 weeks
- When the serum 25(OH)D level exceeds 30 ng/mL, provide maintenance treatment of 400-1000 IU/day
Recommended treatment for vitamin D–deficient patients 1–18 years of age is as follows[4] :
- 2000 IU/day of vitamin D2 or D3 for at least 6 weeks or
- 50,000 IU of vitamin D2 once weekly for at least 6 weeks
- When the serum 25(OH)D level exceeds 30 ng/mL, provide maintenance treatment of 600-1000 IU/day
Recommended treatment for vitamin D–deficient adults is as follows[4] :
- 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks or
- 6000 IU/day of vitamin D2 or D3 for 8 weeks
- When the serum 25(OH)D level exceeds 30 ng/mL, provide maintenance treatment of 1500-2000 IU/day
Recommended treatment for vitamin D–deficient patients who are obese, have a malabsorption syndrome, or are taking medication that affects vitamin D metabolism, is as follows[4] :
- At least 6000-10,000 IU of vitamin D daily
- When the serum 25(OH)D level exceeds 30 ng/mL, provide maintenance treatment of 3000-6000 IU/day
If the 25(OH)D concentration remains persistently low despite several attempts at correction with oral vitamin D, a trial of ultraviolet B light therapy (ie, by tanning lamps) may be considered to improve vitamin D status.
Prevention
Unprotected sun exposure is the major source of vitamin D for both children and adults.[4] Provision of vitamin D from sunlight is as follows:
- Sensible sun exposure, especially between the hours of 10 am and 3 pm, produces vitamin D in the skin that may last twice as long in the blood compared with ingested vitamin D[5]
- Full-body sun exposure producing slight pinkness in light-skinned persons results in vitamin D production equivalent to ingesting 10,000-25,000 IU[6]
- Increased skin pigmentation, aging, and sunscreen use reduce the skin’s vitamin D3 production
Recommended dietary intake of vitamin D for patients at risk of vitamin D deficiency is as follows[4] :
- In infants and children up to 1 year old, at least 400 IU/day, to maximize bone health
- In children and adolescents 1-18 years of age, at least 600 IU/day to maximize bone health
- In adults 19-50 years of age, at least 600 IU/day to maximize bone health and muscle function
- Raising the serum 25(OH)D level consistently above 30 ng/mL may require vitamin D intake of at least 1000 IU/day
- Whether recommended levels of vitamin D intake will provide all the potential nonskeletal health benefits associated with vitamin D is currently unknown
Most dietary sources of vitamin D do not contain sufficient amounts of the vitamin to satisfy daily requirements. The following foods contain the indicated amounts of vitamin D, as reported by the US Department of Agriculture's (USDA's) Nutrient Data Laboratory:
- Fortified milk (8 oz) - 100 IU
- Fortified orange juice (8 oz)[7] - 100 IU
- Fortified cereal (1 serving) - 40-80 IU
- Pickled herring (100 g) - 680 IU
- Canned salmon with bones (100 g) - 624 IU
- Mackerel (100 g) - 360 IU
- Canned sardines (100 g) - 272 IU
- Codfish (100 g) - 44 IU
- Swiss cheese (100 g) - 44 IU
- Raw shiitake mushrooms (100 g) - 76 IU
- Most multivitamins (1 tab) - 400 IU
Follow-up
- After correction of their vitamin D status with oral vitamin D, patients should have a repeat test of their 25(OH)D level to confirm that they are in the normal range. If the 25(OH)D concentration remains persistently low despite several attempts at correction with oral vitamin D, a trial of UVB light therapy (ie, by tanning lamps) may be considered to improve vitamin D status
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