Pathophysiology of Vitamin D

There are three main diseases caused by the deficiency of vitamin-D which are given as follows:

RICKETS:

Rickets is a disorder caused by the deficiency of vitamin D, calcium or phosphate. Rickets lead to softening or weakening of the bones and is seen most commonly in children 6-24 months of age. There are several subtypes of rickets, including hypophosphatemia rickets (vitamin-D-resistant rickets), renal or kidney rickets (renal osteodystrophy), and most commonly, nutritional rickets (caused by dietary deficiency of vitamin D, calcium or phosphate). Classic nutritional rickets is also medically termed as osteomalacia.

CAUSES:

Regardless of the type of rickets, the cause is always either due to deficiency of vitamin D, calcium or phosphate. Three common causes of rickets include nutritional rickets, hypophosphatemic rickets, and renal rickets.

Nutritional rickets

Nutritional rickets, also called osteomalacia, is a condition caused by vitamin D deficiency. Infants and children most at risk for developing nutritional rickets include dark-skinned infants, exclusively breastfed infants, and infants who are born to mothers who are vitamin D deficient. In addition, older children who are kept out of direct sunlight or who have vegan diets may also be at risk.

Hypophosphatemia rickets

Hypophosphatemia rickets is caused by low levels of phosphate. The bones become painfully soft and pliable. This is caused by a genetic dominant X-linked defect in the ability for the kidneys to control the amount of phosphate excreted in the urine. The individual affected is able to absorb phosphate, calcium but the phosphate is lost in the urine.

Renal (kidney) rickets

Similar to hypophosphatemia rickets, renal rickets is caused by the number of kidney disorders. Individuals suffering from kidney diseases often have decreased ability to regulate the amount of electrolytes lost in the urine. This includes calcium and phosphate, and therefore, the affected individuals develop symptoms almost identical to severe nutritional rickets.

SYMPTOMS:

Signs and symptoms of rickets include bone pain or tenderness, dental deformities, delayed formation of teeth, decreased muscle strength, impaired growth, short stature, and a number of skeletal deformities, including abnormally shaped skull (craniotabes) bowlegs, rib-cage abnormalities (rachitic rosary) and breastbone pelvic and spinal deformities.

DIAGNOSIS:

Rickets is initially diagnosed clinically with a complete medical and nutritional history and with a complete physical exam by a health professional. If rickets is suspected in a child and the child has no acute symptoms such as seizures or tetany, X-rays of long bones (radius, ulna and femur) and ribs are obtained.

TREATMENT:

The treatment for rickets depends upon the cause as mentioned above in the discussion of hypophosphatemia rickets and renal rickets. In cases of nutritional rickets and vitamin D deficiency, treatment is simple. Once the diagnosis of rickets is confirmed, initiation of vitamin D supplementation is recommended as well as a diet rich in calcium. This is especially important for children on vegan diets, The treatment for some of the bony abnormalities depends on the severity of the cases and may require referral to the orthopedic provider for evaluation.

OSTEOMALACIA

Osteomalacia is a weakening of the bones due to problems with bone formation or the bone building process. It is not the same as osteoporosis, which is weakening of living bone that has already been formed and is being remodeled.

CAUSES

The most common reason that osteomalacia occurs is a lack of vitamin D. A diet that doesn't include phosphates can result in phosphate depletion, which can also lead to osteomalacia.

Certain drugs, such as phenytoin and phenobarbital used to treat seizures, can also cause osteomalacia.

 SYMPTOMS

Bones that fracture easily are the most common symptom of osteomalacia.

Another symptom is muscle weakness due to problems at the location where the muscle attaches to bone. You may have hard time walking and may develop a waddling gait.

Bone pain, especially in the hips, is also common symptom. This dull, aching pain can spread from the hips to the lower back, pelvis, legs and even ribs. Low blood calcium may also cause numbness around the mouth or in your arms, legs and spasms in hands and feet.

DIAGNOSIS

Blood tests to check for low of vitamin D, calcium, and phosphates in blood can help diagnose osteomalacia and other bone disorders. May be tested for alkaline phosphatase isozymes. High levels of these indicate osteomalacia. Another blood test can check your levels of PTH, high levels of which are associated with insufficient vitamin D and other related problems.

X-rays and other imaging tests can reveal small cracks in the bones throughout the body. These cracks are called Looser's transformation zones. These cracks are where fractures can begin with even small injuries.

A bone biopsy may be required to definitively diagnose osteomalacia. A needle is inserted through the skin and muscle and into your bone to obtain a small sample. That sample is put on a slide and examined under a microscope. Usually, an X-ray and blood test are sufficient to make a diagnose and bone biopsy is not necessary. 

TREATMENT:

Treatment can be as simple as taking oral supplements for vitamin D, calcium or phosphate. If you have absorption problems due to intestinal injury or surgery, or have a diet low in key nutrients, this may be the first line of treatment. In rare cases, vitamin D may be administered as an injection through the skin, or intravenously through a vein in your arm.

OSTEOPOROSIS

It is a progressive bone disease that is characterized by a decrease in bone mass and density and that leads to an increased risk of fracture.

CAUSES:

Osteoporosis occurs when bone tissue and minerals are lost faster than the bone is replaced.

There are two main types of osteoporosis: primary and secondary.

Primary osteoporosis

It occurs most commonly in women after menopause. Osteoporosis affects twice as many females over the age of 70 years as males in the same age group.

Secondary osteoporosis

It can affect young and middle aged people as well. It may be caused by :

• medications such as corticosteroids (e.g., prednisone)
• chronic illness such as anorexia nervosa (eating disorder leads to malnutrition)
• too much exercise- women who exercise excessively lose their menstrual cycle and normal production of estrogen by the ovaries may stop.

SYMPTOMS:

Weakened bones that are no longer able to support body weight can break even under slight pressure. Such fractures most commonly occur in the hipbones, wrists or spine. Hip fractures are more frequent in people over the age of 75 years.

Some fractures caused by osteoporosis, such as hairline breaks in the spine, may cause little or no pain and may go unnoticed, even when they show up on an X-ray. By contrast, spinal crush fractures, where the vertebral column crumbles or collapses, are much more painful and can lead to deformed posture.

Another symptom caused by osteoporosis is chronic back pain. This pain can worsen even when you are making small movements such as regular activities around the house, or while coughing, laughing, or sneezing. You may even feel pain when you are standing still.

DIAGNOSIS:

Bone density measurement by a method called DEXA (dual energy X-ray absorptiometry) is the most effective way to assess osteoporosis risk.

A heel ultrasound test may be used to test bone density and estimate the risk of fracture for women over 65 years of age.

TREATMENTS:

Hormone replacement therapy (HRT) consisting of estrogen alone, estrogen and progesterone, has clearly been found to be useful in reducing menopausal vasomotor symptoms and in reducing the incidence of skeleton fractures. National Institute of Health (NIH) study suggested that HRT may be associated with increased risk of breast cancer in women with a uterus and increased rate of thromboembolic events and stroke.

Three year of 1,25 (OH)2 D3 therapy in woman with post menopausal osteoporosis significantly reduced the incidence of new vertebral fractures as compared with Ca2+ gluconate supplementation.