Vitamin D deficiency is a micronutrient deficiency that leads to a violation of phosphorus–calcium metabolism, anti-infective and antitumor immunity, reproductive functions. D-deficiency in children is clinically manifested by rickets, in adults – osteoporosis, osteomalacia, muscle weakness, immunodeficiency, oncological and vascular diseases, reproductive disorders. The confirmatory diagnosis is based on determining the level of micronutrient in the blood (total vitamin D, 25ON (calciferol), vitamin D metabolites). With proven vitamin deficiency, substitution correction with pharmacopreparations is carried out.
ICD 10
E55 E55.9 M83
Meaning
Hypovitaminosis D is a deficiency of various forms of fat‒soluble vitamin, primarily ergocalciferol ‒ D2 and cholecalciferol ‒ D3. Vitamin D deficiency (serum content <30 ng/ml) is determined in 50-92% of the world’s population, depending on socio-economic conditions and the region of residence. Critical deficiency (<10 ng/ml) is typical for residents of Middle Eastern and South Asian countries. Low levels of vitamin D are observed in all age categories, but postmenopausal women are the most at risk – D deficiency occurs in more than 75% of them.
Causes of vitamin D deficiency
Fat-soluble vitamin D is present in the body in two main forms: D2 comes exclusively from food, D3 is synthesized in the skin under the influence of UV rays and is contained in food products. Micronutrient deficiency develops due to its insufficient endogenous synthesis or exogenous intake, which is facilitated by:
- Climatic conditions. Geographically, most of the territory of the Russian Federation is located in the northern latitude. A limited number of sunny days a year and low temperatures in the autumn-winter period lead to the fact that from November to March, endogenous vitamin D is practically not produced in the skin. The use of sunscreens reduces the synthesis of vitamin D by more than 90%.
- Features of the diet. The risk of vitamin deficiency is increased in patients with lactase deficiency, allergy to milk protein. At risk are adherents of vegetarianism, people with a monotonous diet, in whose diet there is no fatty fish, dairy products, eggs, mushrooms.
- Impaired absorption and metabolism. The formation of hypovitaminosis D is facilitated by the malabsorption of fats observed in patients with NYC, Crohn’s disease, celiac disease, cystic fibrosis, radiation enterocolitis. A similar problem is faced by people who have undergone bariatric intervention.
- Increased consumption of micronutrient. An increase in the loss of protein associated with 25(OH)D is noted in nephrotic syndrome. Acceleration of vitamin D catabolism causes the intake of anticonvulsants, corticosteroids, and antiretroviral drugs. Increased consumption of nutrient reserves is noted in granulomatous lung lesions (sarcoidosis, tuberculosis, berylliosis), fungal infections (coccidiomycosis, histoplasmosis).
- Defects in the vitamin D receptor gene. Decreased sensitivity to vitamin in some cases may be caused by genetic mutations of the VDR gene on chromosome 12q12-q14. With VDR defects, the binding of the protein of the same name with vitamin D is disrupted, as a result of which calcium metabolism suffers. This condition is manifested by vitamin D-resistant rickets, pathological fractures, primary hyperparathyroidism.
Risk factors
Certain conditions and diseases are associated with a higher risk of vitamin D deficiency. The category of persons primarily in need of biochemical screening includes:
- pregnant and lactating: especially in the presence of gestational diabetes, obesity, refusal of preventive vitamin D supplementation;
- elderly people: people over 65 years of age have a 4-fold decrease in the synthesis of endogenous vitamin D;
- dark-skinned: melanin protects the skin from solar insolation and reduces the ability to synthesize cholecalciferol;
- patients with chronic diseases: CRF, malabsorption, obesity, lung infections.
Pathogenesis
Two forms of vitamin D have the greatest biological significance for the body: ergocalciferol (D2) and cholecalciferol (D3). When exposed to UV rays on the skin, 7-dehydrocholesterol is converted into provitamin D3. One part of provitamin is transformed into vitamin D3, the other into its inactive metabolites tachysterol and lumisterol. 80% of cholecalciferol is synthesized in the skin under the influence of sunlight, 20% comes from animal food (liver, fish oil, egg yolk). Ergocalciferol is found only in food sources – bread, mushrooms.
However, both exogenously supplied and endogenously produced vitamin D are initially biochemically inert, and double hydroxylation is necessary for their activation. The first stage takes place in the liver, where vitamin D is transformed into 25-hydroxyvitamin D (calcidiol, 25(OH)D). At the second stage, which occurs in the kidneys, 25 (HE)D with the participation of the renal enzyme 1-alpha-hydroxylase becomes the active form ‒ 1,25-dihydroxyvitamin D (calcitriol, 1,25(OH)2D, D-hormone).
With a deficiency of D-hormone, the absorption of calcium and phosphates in the intestine decreases. In response to this, the synthesis of parathyroid hormone increases, with the help of which the body compensates for the lack of calcium by extracting it from the bone depot and increasing the renal excretion of phosphorus. Increased activation of osteoclasts causes a violation of mineralization and resorption of bone tissue. Against this background, skeletal deformities occur in young children, rickets develops. In adults, vitamin D deficiency is accompanied by osteomalacia, a tendency to falls and pathological fractures.
In addition to the intestine, vitamin D receptors are expressed in many organs and cells that are sensitive to its deficiency. With D-hypovitaminosis, the homeostasis of the immune system is disrupted: autoimmune pathologies, infections, and malignant neoplasms develop more often. There is evidence of the relationship of low vitamin D levels with the incidence of cardiovascular diseases. D-vitamin deficiency is associated with impaired reproductive function, cognitive deficits.
Classification
The International Endocrinological Society determines an adequate level of vitamin D in the range of 30-100 ng/ml. Taking into account the deviation from the reference value, hypovitaminosis D can be expressed in the following degree:
- D-vitamin deficiency (<30 ng/ml) ‒ low risk of secondary hyperparathyroidism (SPT), bone resorption, bone fractures;
- D-deficiency (<20 ng/ml) ‒ the risk of the above events is increased;
- Pronounced D-deficiency (<10 ng/ml) ‒ significantly increased risk of rickets, myopathy, osteoporosis, fractures.
Symptoms of vitamin D deficiency
Bone manifestations
The D-deficient symptom complex consists of classical (bone) and extra-bone effects. In infancy, bone lesions are clinically manifested by rickets. First of all, pathological changes are found in the bones of the skull: there is a softening of the flat bones (craniotabes), hypertrophy of the frontal and parietal tubercles develops. A large fontanel does not overgrow for a long time, teeth erupt late.
In the second half of life, changes in the bones of the skeleton become noticeable. Bone thickenings form on the ribs – “rickety rosaries”, there is a deformation of the chest (keeled, funnel-shaped). The phalanges of the fingers thicken in the form of “strings of pearls”, bone growths – “bracelets” are formed in the area of the wrists. The lower limbs are bent (varus, valgus deformity), the spine (thoracic kyphosis). Muscle hypotension, delayed motor development, anemia, dystrophy are characteristic.
Vitamin D deficiency in adults is manifested by osteomalacia and osteoporosis. Against the background of a decrease in bone strength, diffuse bone pain, muscle weakness, gait and balance disorders occur. Falls are becoming more frequent, which increases the risk of fractures of the bones of the wrist, hip neck, compression fractures of the spine. Over time, bone deformities occur in the vertebral column, chest, pelvis, and lower extremities.
Extra – skeletal manifestations
Non-calcemic consequences of D-deficiency are associated with dysfunction of the immune, endocrine, cardiovascular, and nervous systems. With a lack of micronutrient in the blood, the content of “bad” cholesterol increases against the background of a decrease in HDL, dyslipidemia, atherosclerosis develops. Vascular tone changes, which causes the development of arterial hypertension. The synthesis of insulin and the sensitivity of peripheral tissues to it is disrupted, resulting in insulin resistance, diabetes mellitus.
Vitamin D is known to be involved in the regulation of cell proliferation and apoptosis, and its deficiency is associated with more frequent development of cancer pathology. In particular, the association of micronutrient deficiency with prostate, ovarian and uterine cancers, stomach, pancreas and colon, bladder, breast cancer, lymphoma, myeloma was found.
D-hypovitaminosis leads to dysregulation of the immune system, which increases the risk of the occurrence and severe course of infectious diseases: tuberculosis, ARVI. Against the background of vitamin deficiency, autoimmune pathologies occur significantly more often: SLE, rheumatoid arthritis, atopic bronchial asthma, psoriasis.
Vitamin D has a cerebroprotective effect, reducing damage to neurons and myelin sheaths. D-deficiency is partly associated with the development of multiple sclerosis, neurodegenerative diseases, autism, depression.
With vitamin D deficiency, the reproductive function suffers significantly. In men, the qualitative and quantitative indicators of sperm decrease, hypogonadism, androgen deficiency, BPH develops. In women, vitamin deficiency is associated with the development of endometriosis, uterine fibroids, PCOS, a high frequency of gestational complications, and IVF failures.
Complications
In children who have had rickets, there are residual deformities of the bones of the skeleton: flat feet, scoliosis, narrow pelvis, curvature of the sternum and ribs, leading to a decrease in VEL. Vitamin D deficiency, which develops in old age, is dangerous for pathological fractures, severe motor function disorders up to sarcopenia and immobilization.
Violation of lipid metabolism is a risk factor for the development of strokes, MI, increased mortality from cardiovascular disasters. In addition, adverse outcomes may be associated with a complicated course of infections, the progression of oncological diseases.
Diagnostics of vitamin D deficiency
The main method of recognizing vitamin D deficiency is to determine its serum level. The results of the analysis are interpreted in conjunction with complaints and objective data. The examination prescribed by a general practitioner includes.
The study of the level of vitamin D. Screening analysis is the determination of the concentration of 25(OH)D (reference values of 30-100 ng/ml). In addition, it may be necessary to conduct a comprehensive analysis for vitamins D2 and D3, vitamin metabolites (1,25‑OH D3, 25‑OH D2, 25‑OH D3, etc.)
and other analyzes. To obtain a complete picture of the state of mineral metabolism, it is advisable to determine serum calcium, phosphorus, magnesium, PTH, ostase. D-resistant rickets can be excluded by detecting mutations of the vitamin D receptor gene.
Examination of the bone system. In case of skeletal deformities and fractures, radiography of tubular bones, skull bones, pelvis, spine, chest is shown. To study the bone mineral density, ultrasound or X-ray osteodensitometry is performed.
Treatment for vitamin D deficiency
The main directions of correction of hypovitaminosis D are the revision of the diet and the intake of vitamin preparations. Nutritionists and endocrinologists work with patients with vitamin D deficiency. Within the framework of conservative therapy , the following are shown:
- Diet therapy. Food sources of micronutrient are fish (salmon, herring, tuna, sardine, mackerel), milk, butter, sour cream, egg yolk, mushrooms, beef liver. However, the daily need for vitamin, as a rule, is not covered only by diet, especially with impaired liver, kidney function, malabsorption.
- Taking vitamin D preparations is a mandatory component of vitamin D deficiency therapy. Preparations in the form of cholecalciferol (D3) and ergocalciferol (D2) are used. The dose and duration of administration depends on age, severity of vitamin deficiency, concomitant conditions, climatic conditions. First, the drugs are prescribed in saturating doses, then in supporting ones. If necessary, calcium-containing additives are used.
- Physical rehabilitation. For rickets, massage with elements of therapeutic gymnastics, general UFO is recommended. Sea and coniferous baths are useful. Methods of restorative treatment of adults with the consequences of vitamin D deficiency include motor rehabilitation: exercise therapy, dosed walking, hydrokinesotherapy. Massage, ozone therapy, electrophoresis, myostimulation, ultrasound therapy are performed.
Prognosis and prevention
Low D-vitamin status is associated with multiple disorders of the musculoskeletal, endocrine, immune, nervous, and cardiovascular systems. This is due to increased morbidity, disabling consequences, premature death from socially significant diseases: vascular catastrophes, cancer, tuberculosis, etc.
As a prevention of hypovitaminosis D, it is recommended to stay in the sun during the warm season for 5-15 minutes twice a day without using sunscreen. It is advisable to use daily foods enriched with vitamin D, preventive intake of micronutrient preparations from October to March inclusive.
Literature
- Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. J Pharmacol Pharmacother. 2012 Apr;3(2):118-26. link
- Holick MF. Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. South Med J. 2005 Oct;98(10):1024-7. link
- Czernichow S, Fan T, Nocea G, Sen SS. Calcium and vitamin D intake by postmenopausal women with osteoporosis in France. Curr Med Res Opin. 2010 Jul;26(7):1667-74. link
- Naeem Z. Vitamin d deficiency- an ignored epidemic. Int J Health Sci (Qassim) 2010 Jan;4(1):V-VI. link
- Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998 Mar 19;338(12):777-83. – link
