Vitamin D deficiency can result from inadequate sunlight exposure, low dietary intake, or impairments in vitamin D metabolism. It causes rickets in children as their bones fail to properly mineralize, while in adults it causes osteomalacia marked by bone pain and fractures. Risk factors include liver or digestive diseases, certain drugs, and genetic mutations impacting vitamin D metabolism. Osteoporosis involves low bone density and increased fracture risk related to aging and declining estrogen levels along with impaired vitamin D function.

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
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

4. Privational causes
These involve inadequate vitamin D supply:
❍ Inadequate exposure to sunlight
❍ Insufficient consumption of food
sources of vitamin D
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

5. Nonprivational causes
These relate to impairments
in the absorption,
metabolism or nuclear
binding of the vitamin.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

7. Nonprivational causes
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

8. 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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

9. Nonprivational causes
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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
1,25-(OH)2-D3 or 1α-OH-D3.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

14. Signs of vitamin D deficiency
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

17. Rachitic rosary
Mediphotos.com
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

18. Sabre tibia
Musculoskeletalkey.com
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

23. Osteomalacia
Radiopaedia.org
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

24. Rickets vs. osteomalacia
Organ system Rickets Osteomalacia
General Loss of appetite, retarded growth None
Dermatologic None None
Muscular Weakness 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 None None
Nervous Tetany, ataxia None
Reproductive None Low sperm motility and number
Ocular None None
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

26. Osteoporosis
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

28. 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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

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.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

30. Literature
• Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.