1. Vitamin D deficiency
Domina Petric, MD

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Nonprivational causes
Exposure to certain drugs (the anticonvulsives phenobarbital, diphenylhydantoin), which induce the catabolism of 25-OH-D3 and ,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

9. 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

10. 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 ,25-(OH)2-D3 or 1α-OH-D3.
September 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. 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

12. 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

13. 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

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

15. 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

16. 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

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

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

19. 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

20. 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

21. 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

22. 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

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

24. 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

25. 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

26. 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

27. 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

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

29. 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

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