The most common nutritional deficiency worldwide, characterised by serum 25-hydroxyvitamin D <50 nanomol/L (<20 nanograms/mL). Vitamin D insufficiency is regarded as a serum 25-hydroxyvitamin D level between 52 and 72 nanomol/L (21 and 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 analogues is necessary for those with disorders of vitamin D metabolism.
To maximise vitamin D effects on the skeleton and on calcium metabolism, serum 25-hydroxyvitamin D level should be >75 nanomol/L (>30 nanograms/mL). Therefore, vitamin D deficiency is defined as a serum 25-hydroxyvitamin D level of <50 nanomol/L (<20 nanograms/mL), whereas vitamin D insufficiency is regarded as a 25-hydroxyvitamin D level of between 52 and 72 nanomol/L (21 and 29 nanograms/mL).    
Vitamin D deficiency is the most under-diagnosed 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 in rising from a sitting position).
In addition to the skeletal effects, it is now recognised that vitamin D deficiency increases the risk of many chronic diseases, including cancer, autoimmune diseases, type 2 diabetes, heart disease and hypertension, infectious diseases (including upper respiratory tract infections and tuberculosis), and osteoarthritis, as well as depression and schizophrenia. 
Program Director for the General Clinical Research Unit (GCRU)
Professor of Medicine, Physiology, and Biophysics
Department of Medicine
Section of Endocrinology, Diabetes, and Nutrition
Vitamin D, Skin, and Bone Research Laboratory
Boston University School of Medicine
MFH declares that he has no competing interests. MFH is an author of a number of references cited in this monograph.
Assistant Professor of Medicine
Division of Endocrinology
Metabolism and Lipids
Emory University School of Medicine
VT is an author of a reference cited in this monograph.
General Practitioner (GP)
Resident at the Department of Internal Medicine
Division of Endocrinology and Nuclear Medicine
Medical University of Graz
SP is an author of a reference cited in this monograph.
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