The most common nutritional deficiency worldwide, characterized by serum 25-hydroxyvitamin D <20 nanograms/mL. Vitamin D insufficiency is regarded as a serum 25-hydroxyvitamin D level between 21-29 nanograms/mL.
Main causes include sun avoidance, using sun protection, increased skin pigmentation, inadequate dietary and supplemental vitamin D intake, malabsorption syndromes, obesity, and medication use.
Acquired and inherited disorders that either reduce or prevent the metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D also present with biochemical and skeletal abnormalities seen with vitamin D deficiency, but in a more severe form.
Most patients are asymptomatic. Severe prolonged vitamin D deficiency causes growth retardation and rickets in children and osteomalacia, osteopenia, and osteoporosis in adults.
Both vitamin D deficiency and vitamin D insufficiency are corrected by giving vitamin D2 or vitamin D3 in treatment doses followed by lifelong maintenance doses; adequate, sensible sunlight exposure should be encouraged.
Additional replacement with 1,25-dihydroxyvitamin D or one of its active analogs is necessary for those with disorders of vitamin D metabolism, including patients with chronic kidney disease.
To maximize vitamin D effects on the skeleton and on calcium metabolism, serum 25-hydroxyvitamin D level should be >30 nanograms/mL. Therefore, vitamin D deficiency is defined as a serum 25-hydroxyvitamin D level of <20 nanograms/mL, whereas vitamin D insufficiency is regarded as a 25-hydroxyvitamin D level of between 21-29 nanograms/mL.
Vitamin D deficiency is the most underdiagnosed medical condition in children and adults. This is largely because patients do not typically present with overt clinical signs and symptoms until the deficiency is severe and prolonged. Children with established vitamin D deficiency present with features of rickets (skeletal abnormalities, developmental delay, failure to thrive), whereas adults present with signs and symptoms of osteomalacia (bone pain and tenderness, proximal muscle weakness reported as difficulty rising from a sitting position).
In addition to the skeletal effects, it is now recognized that vitamin D deficiency increases the risk of many chronic diseases, including cancer, autoimmune diseases, type 2 diabetes, heart disease and hypertension, neurocognitive dysfunction, infectious diseases (including upper respiratory tract infections and tuberculosis), and osteoarthritis, as well as depression and schizophrenia.
History and exam
- inadequate sunlight exposure
- increased skin pigmentation
- age >50 years
- history of inadequate dietary and supplemental vitamin D intake
- history of malabsorption
- medication use, including antiseizure medications, glucocorticoids, and AIDS medications
- history of benign or malignant tumor
- history of chronic kidney disease
- bowing of the legs
- widening of the ends of the long bones
- delayed tooth eruption and early dental caries
- chest deformity
- throbbing, aching bone discomfort and/or irritability
- head sweating
- localized or generalized bone tenderness
- proximal muscle weakness
- rachitic rosary
- frontal bossing
- waddling gait
Michael F. Holick, PhD, MD
Director Bone Healthcare Clinic
Director Ehlers-Danlos Clinical Research Program
Professor of Medicine, Physiology, and Biophysics
Departments of Medicine, Physiology, and Biophysics
Section of Endocrinology, Diabetes, and Nutrition
Vitamin D, Skin, and Bone Research Laboratory
Boston University School of Medicine
MFH is a consultant for Quest Diagnostics and a speaker for Abbott. He also chaired the Endocrine Society’s practice guidelines on vitamin D. MFH is an author of references cited in this topic.
Vin Tangpricha, PhD, MD
Professor of Medicine
Division of Endocrinology
Metabolism and Lipids
Emory University School of Medicine
VT is an author of references cited in this topic.
Stefan Pilz, MD
Resident at the Department of Internal Medicine
Division of Endocrinology and Nuclear Medicine
Medical University of Graz
SP is an author of references cited in this topic.
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