Vitamin D Deficiency Rickets by azr57762


									Vitamin D Deficiency Rickets

The resident should be able to differentiate between osteomalacia and rickets, know the
pathophysiology behind rickets, know how to evaluate, diagnose and treat Vit D deficiency
rickets in children, recognize who is at highest risk for rickets, and delineate management steps
that can prevent the occurrence of rickets in children at risk.

The mother of an 18 month old African-American boy expressed concern during a routine health
supervision visit that her son had not begun to walk. He had been breastfed through 9 months of
age and since weaning had received very little dairy products or vitamin D. His weight was
9.8kg (<5th percentile) and he had bilateral wrist enlargement, lower limb bowing and frontal
Laboratory studies demonstrated decreased phosphorus, decreased calcium, elevated alk
phosphate, decreased hydroxyvitamin D, and increased dihydroxyvitamin D. Serum creatinine
values were normal.
Radiographs showed severe osteopenia of the skeleton, with fraying and cupping of the
metaphyses, especially in the wrists, and widening of the physes.

  1. What is the difference between rickets and osteomalacia?
  2. What are the different types of rickets?
  3. How does one evaluate and diagnose Vitamin D deficiency rickets in children?
  4. How does one treat a child with rickets, and what is the prognosis of someone who has
  5. How can one prevent rickets?

   1. Agus, Z. Causes of vitamin D deficiency and resistance.
      December 2003
   2. Joiner, T., Foster, C., Shope, T., The Many Faces of Vitamin D Deficiency Rickets.
      Pediatrics in Review. 2000; 21:296-302.
   3. Gartner, L., et al, Prevention of Rickets and Vitamin D Deficiency: New Guidelines for
      Vitamin D Intake. Pediatrics. 2003; 111:908-910.
   4. Rauch, F. Overview of rickets in children. December
   5. Rauch, F. Etiology and treatment of hypocalcemic rickets in children. December 2003.
   1. What is the difference between osteomalacia and rickets?


   Osteomalacia: disorder of mineralization of newly formed matrix in adults

   Rickets: Defective mineralization of cartilage taking place in the epiphyseal growth plate,
   leading to widening of the long ends of bones, growth retardation, and skeletal deformities in

   Rickets and osteomalacia usually occur together as long as the growth plates are open; only
   osteomalacia occurs after the growth plates have fused.

   2. What are the different types of rickets?
        a) Vitamin D dependent-caused by reduced activity of 25 hydroxy alpha-
            hydroxylase (enzyme that activates vitamin D)
        b) Vitamin D deficiency- “classical rickets” caused by low endogenous vitamin D
        c) Vitamin D resistant- defect in tubular reabsorption of phosphate

          In children, vitamin D deficiency is the most common cause of rickets, thus we will
          focus on that particular entity.

   Vitamin D is the prohormone that is activated into two forms:
   a) Cholecalciferol (D3)- produced endogenously in skin after UV B exposure
   b) Ergocalciferol (D2)- obtained exogenously from diet.

   These activated forms of vitamin D (D2 and D3) are then hydroxylated in the liver and
   changed to 25 hydroxy vit D, which subsequently are hydroxylated in the kidney to 1,25
   dihydroxyvitamin D via the enzyme 1-alpha-hydroxylase. 1,25 dihydroxyvitamin D causes
   increased Ca absorption from the intestine as well as helps mobilize calcium and phosphorus
   from bone.

   When things go wrong:
   Initial days to weeks:
   As a patient becomes increasingly more Vit D deficient, there are decreased levels of Ca
   absorbed in the intestines decreased levels of Ca in blood levels of 25 hydroxy vit D
   decrease, which causes an increase in parathyroid hormone so as to raise serum calcium
   levels. PTH increases the activity of the enzyme 25 hydroxyvitamin D 1-alpha
   hydroxylase increases 1,25 dihydroxyvitamin D increases mobilization of Ca from bone
   matrix. As a result of this, clinical bony manifestations become more evident, including
   rachitic bone changes.
Weeks to months:
Calcium salts are mobilized from the bone and the bone begins to break down. This causes
the elevated serum alkaline phosphatase and further bone matrix breakdown
After 3 months:
Get an eventual decrease in both serum calcium and phosphorus despite the increase in PTH,
because mineral absorption no longer able to support normal serum calcium. Bone is thus
unable to calcify (without Ca and Phos) and get frayed zone of nonrigid tissue (“rachitic
metaphysis”). The zone is characterized by flaring of ends of bones and the “rachitic rosary”
on physical exam.

3. How does one evaluate and diagnose Vitamin D deficiency rickets in children?

       a) Obtain good history- especially dietary, with particular attention given to breast
           feeding, calcium & vitamin D intake, and take a medication history. Of note,
           infants who consume 17 oz (~0.5L) of formula daily get 200IU of vitamin D
           (recommended daily allowance by the American Academy of Pediatrics). Levels
           of vitamin D in breast milk range from 12 to 60 IU/L. Thus, if the intake of
           vitamin D fortified milk or formula is <500 mL per day, a vitamin D supplement
           can be provided by giving a multivitamin preparation containing 400IU of
           vitamin D per mL or tablet(i.e. trivisol).
       b) Perform a physical exam (see below)
       c) Draw labs: Drawing total serum and ionized calcium, phosphorus, alkaline
           phosphate, parathyroid hormone, creatinine (necessary to exclude renal
           insufficiency as the primary etiology), liver enzymes (necessary to exclude liver
           disease as etiology of elevated alk phos activity),

Clinical manifestations of rickets:
The site and type of deformity of the extremities in children depends upon the childs age and
his or her weight bearing patterns in the limbs. For example, in toddlers, exaggeration of
bowing of legs is common for a pt who has started to walk. In older children, windswept
deformity (valgus deformity of one leg and varus deformity of the other leg) may be apparent

Skeletal Findings
Flaring of bones at the distal forearm, knee and costochondral junctions- they are the site of
rapid bone growth, where significant quantities of both calcium and phosphorus are required
for mineralization

Delay in closure of fontanelles, parietal and frontal bossing, craniotabes, enlargement of the
costochondral junction continues, enlargement of the wrist and bowing of the distal radius
and ulna, and progressive lateral bowing of the femur and tibia.
Extraskeletal findings
Hypocalcemic rickets: Hypoplasia of dental enamel, decreased muscle tone developmental
delay, seizures (severe hypocalcemia), and increased sweating in young infants

Laboratory findings
Elevated:                                                 Decreased:
Alkaline phosphatase                                      Calcium*
Parathyroid hormone                                       phosphorus
Dihydroxyvitamin D                                        hydroxyvitamin D

* If vitamin D deficiency is highly suspected, need to determine if child is at risk for
convulsions or tetany related to low calcium levels

Radiographic findings
Changes of rickets are best visualized at the growth plate of rapidly growing bones.

Upper limbs: Distal ulna is the site that best demonstrates the early signs of impaired

Lower limbs: the metaphyses above and below the knees-most useful in older children
Progression of changes:
Widening of epiphyseal plate further disorganization of growth plate, with cupping,
splaying, and cortical spurs the shafts of the long bones become osteopenic and cortices
become thin deformities of the shafts of the long bones are present may see pathologic
fractures. Don’t forget: in evaluating a child for rickets, if he/she is found to have
multiple fractures, one still needs to consider nonaccidental trauma as a potential cause.

Dependent on history, physical exam, and lab values to determine etiology of rickets.

Hypocalcemic rickets is typically caused by a deficiency of vitamin D, as previously
described. Other possibilities include defect of 1-alpha-hydroxylase (the enzyme that
activates vitamin D), dysfunction of the vitamin D receptor, dietary calcium deficiency, and
chronic renal failure.

Hypophosphatemic rickets (vitamin D resistant rickets) in children and adolescents is almost
always caused by renal phosphate wasting, which may be isolated or part of a generalized
tubular disorder such as Fanconi syndrome or Dent disease.

4. What is the treatment of rickets and what is the prognosis of someone who has

Most importantly: It is extremely important to prevent complications of hypocalcemia,
including tetany and convulsions. Patients who have critically low calcium and phosphorus
levels must have the hypocalcemia corrected with supplemental calcium
Once laboratory and radiologic tests confirm the diagnosis of vitamin D deficiency rickets,
vitamin D oral supplementation (800 to 1000IU/d) until serum alkaline phosphate levels and
skeletal deformities return to normal. Calcium should also be supplemented (1000mg/day).
Additionally, recommending a diet rich in calcium is advisable.

Outcomes for children diagnosed with early vitamin D deficiency rickets are good. Early
diagnosis will prevent sequelae such as motor developmental delay. The healing process
initiates within a few days with supplementation with sufficient amounts of vitamin D, and
progresses slowly over several months. Bony abnormalities slowly resolve but may persist
for months to years during treatment.
In cases where rickets is advanced, however, knock-knees, curvature of the upper
extremities, chest deformities, rachitic pelvis, coax vara and short stature may be permanent

5. How can one prevent rickets?

There are currently no clear recommendations about whether or how to screen for rickets.
Both patients and physicians need to be aware if they or their patients are at risk.

Risk factors include:
a) Darker skinned ethnic groups (due to decreased concentration of vitamin D compared to
   lighter skinned women)
b) Exclusively breast fed babies without vitamin D supplementation (26% of all babies in
   US are still being breast fed by 6 months of age)
c) Low milk/dairy product intake and/or vegan diet
d) Living in cold climates (decreased sunlight exposure). Note: As most physicians advise
   caution in sun, increasing your vitamin D intake via sunbathing is not advised. Also,
   consider that the application of sunscreen markedly decreases vitamin D production in
   the skin.

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