Vitamin D deficiency Domina Petric, MD

Causes of vitamin D deficiency Vitamin D deficiency can result from: inadequate irradiation of the skin insufficient intake from the diet impairments in the metabolic activation (hydroxylations) of the vitamin September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Causes of vitamin D deficiency Most people show strong seasonal fluctuations in plasma 25-OH-D3 concentration. Vitamin D deficiency can have privational and/or nonprivational causes. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Privational causes These involve inadequate vitamin D supply: ❍ Inadequate exposure to sunlight ❍ Insufficient consumption of food sources of vitamin D September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes These relate to impairments in the absorption, metabolism or nuclear binding of the vitamin. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Diseases of the gastrointestinal tract (small bowel disease, gastrectomy, pancreatitis), involving malabsorption of the vitamin from the diet. Diseases of the liver (biliary cirrhosis, hepatitis), involving reduced activities of the 25-hydroxylase. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Diseases of the kidney (nephritis, renal failure), involving reduced activities of the 1-hydroxylase, the major source of 1,25-(OH)2-D3,99 or of 25-OH-D3 as in individuals with nephrotic syndrome who lose 25-OH-D3 along with its globulin-binding protein into the urine. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Exposure to certain drugs (the anticonvulsives phenobarbital, diphenylhydantoin), which induce the catabolism of 25-OH-D3 and 1,25-(OH)2-D3, reduce circulating levels of the former, and reduce elevated PTH levels. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Impaired parathyroid function resulting in hypoparathyroidism (reduced production of PTH), which impairs the ability to respond to hypocalcemia by increasing the conversion of 25-OH-D3 to 1,25-(OH)2-D3. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Genetic mutations resulting in impaired expression of the renal 25-(OH)-D3-1 hydroxylase in the condition referred to as vitamin D-dependent rickets type I, which can be managed using low doses of 1,25-(OH)2-D3 or 1α-OH-D3. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Expression of a nonfunctional VDR and impairing the transcription of vitamin D regulated genes involved in Ca and phosphorus homeostasis in the condition referred to as vitamin D-dependent rickets type II, the management of which requires relatively high doses of 1,25-(OH)2-D3 or 1α-OH-D3. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Resistance of PTH target cells, resulting in pseudohypoparathyroidism and involving hypocalcemia without compensating renal retention or bone mobilization of Ca despite normal PTH secretion. The condition responds to low doses of 1,25-(OH)2-D3 or 1α-OH-D3. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nonprivational causes Vitamin D-resistance involving: impaired phosphate transport in the intestine and reabsorption in the proximal renal tubules hypersensitivity to PTH impaired 1-hydroxylation of 25-OH-D3 The condition responds to phosphate plus either high-dose vitamin D3 (25,000–50,000 IU/day) or low doses of 1,25-(OH)2-D3 or 1α-OH-D3. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Signs of vitamin D deficiency September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Rickets Rickets first appears in 6- to 24-month-old children, but can manifest at any time until the closure of the bones’ epiphyseal growth plates. It is characterized by impaired mineralization of the growing bones with accompanying bone pain, muscular tenderness and hypocalcemic tetany. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Rickets Tooth eruption may be delayed. The fontanelle may close late. Knees and wrists may appear swollen. Affected children develop deformations of their softened, weight-bearing bones, particularly those of the legs: bowleg, knock knee and sabre tibia. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Rachitic rosary Mediphotos.com September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Sabre tibia Musculoskeletalkey.com September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Rickets Radiography reveals enlarged epiphyseal growth plates resulting from their failure to mineralize and continue growth. Rickets is most frequently associated with low dietary intakes of calcium, as in the lack of access to or avoidance of milk products. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteomalacia Osteomalacia occurs in older children and adults with formed bones whose epiphyseal closure has rendered that region of the bone unaffected by vitamin D deficiency. The signs and symptoms of osteomalacia are more generalized than those of rickets: muscular weakness and bone tenderness and pain particularly in the spine, shoulder, ribs or pelvis September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteomalacia Lesions involve the failure to mineralize bone matrix, which continues to be synthesized by functional osteoblasts. The condition is characterized by an increase in the ratio of non-mineralized bone to mineralized bone. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteomalacia Radiographic examination reveals abnormally low bone density (osteopenia) and the presence of pseudofractures, especially in the spine, femur and humerus. Patients with osteomalacia are at increased risk of fractures of all types, but particularly those of the wrist and pelvis. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteomalacia Radiopaedia.org September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Rickets vs. osteomalacia Organ system Rickets Osteomalacia General Loss of appetite, retarded growth None Dermatologic Muscular Weakness Skeletal Failure of bone to mineralize: deformation, swollen joints, delayed tooth eruption, bone pain, tenderness Demineralization of formed bone: fractures, pseudofractures, bone pain, tenderness Vital organs Nervous Tetany, ataxia Reproductive Low sperm motility and number Ocular September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteoporosis It is characterized by decreased bone mass with retention of normal histological appearance. It is considered a multifactorial disease associated with aging and involving impaired vitamin D metabolism and/or function associated with low or decreasing estrogen levels. The disease is the most common bone disease of postmenopausal women and also occurs in older men and patients on chronic corticosteroid therapy. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteoporosis High incidence of fractures, especially of the vertebrae, hip, distal radius and proximal femur. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteoporosis In women, osteoporosis is characterized by rapid loss of bone (0.5–1.5% per year) in the first 5 to 7 years after menopause. The increased skeletal fragility observed in osteoporosis does not appear to be due solely to reductions in bone mass, but also involves changes in skeletal architecture and bone remodeling: losses of trabecular connectivity as well as inefficient and incomplete microdamage repair. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Osteoporosis Affected individuals show abnormally low circulating levels of 1,25-(OH)2-D3. Estrogen loss may impair the renal 1-hydroxylation step: the disease involves a bihormonal deficiency. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Musculoskeletal pain Nonspecific musculoskeletal pain may occur among adults with low circulating levels of 25-OH-D3 but not showing signs of osteomalacia or osteoporosis. It has been suggested that pain may be an early sign of severe hypovitaminosis D. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. September 17, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.