Rickets

Introduction

Rickets is defined as the failure to mineralize growing bone.  The two principle substances necessary for bone mineralization are calcium and phosphate, both of which are influenced by Vitamin D. 

Vitamin D2, (ergocalciferol) is found in some plants and fish. Vitamin D3, (cholecalcifereol) is consumed in milk and formed in sun-exposed skin from 7-dehydrocholesterol.  90% of our vitamin D comes from sun exposure. It is activated by ultraviolet rays to cholecalciferol and transferred to the liver. The liver hydoxylates Vit D2 and Vit D3  to 25-OH-cholecalciferol and the kidneys convert it to 1,25- dihydroxycholecalciferol, the most potent active agent. 

Vitamin D deficiency rickets is still prevalent in the United States.  The majority of cases occur in strictly breastfed infants who are not being supplemented with vitamin D. The AAP recommends supplementation but a recent survey demonstrated that approximately 30% of breastfed infants were not receiving any.  Other susceptible individuals include dark skinned individuals and those living in northern latitudes that do not come in contact with sunlight. Strict vegans are also susceptible to rickets because they do not eat dairy products. 

 

Pathophysiology

In a vitamin D deficient state, Ca reabsorption decreases to 10-15%, leading to low iCa levels that stimulate PTH secretion. PTH stimulates (1) Ca reabsorption in the renal tubules,  (2) 1-alpha-hydroxylase activity, which leads to increased 1,25-OH vitD synthesis, and (3) phosphate loss in the urine. Together, these decrease bone mineralization and prevent apoptosis of hypertrophied chondrocytes, leading to disorganized growth plate cartilage.  The clinical presentation is termed osteomalacia in mature bones, but rickets in immature bones. 

 

Presentation

The presentation of rickets is described as three stages:

  1. Osteopenia with overt hypocalcemia: this is a very transient phase.
  2. Increases in PTH levels with normal/low Ca levels, leading to bone pain
  3. Reappearance of overt hypocalcemia with gross bone dysfigurement.

 

Clinical Manifestations

  1. Constitutional deformities
    • Decreased linear growth
    • Failure to thrive
  2. MSK deformities
  3. Neurologic abnormalities
    • Hypotonia
    • Brisk reflexes - Trousseau and Chvostek's sign
    • Weak respiratory muscles: apnea, wheezing
  4. Vitamin D deficiency is also associated with autoimmune diseases such as multiple sclerosis, or Type 1 DM.

 

Laboratory Findings

  1. Low or normal Ca++(Depends on the phase of presentation, as PTH tries to normalize serum levels)
  2. Low phosphorus
  3. Elevated alkaline phosphatase
  4. Low 25-OH-Vit D and normal or increased 1,25-dihydroxy Vit D
    • 25-OHD has a longer half life and is in general more accurate in predicting vitamin D status.
    • 25-OHD < 50 ng/mL is deemed insufficient, with <= 37.5 ng/mL deemed deficient.
  5. Increased PTH

 

Radiograph Findings

  1. Osteopenia
  2. Metaphysis widening, cupping, and fraying
    wt.png
    http://www.thachers.org/rickets_photos.htm
    sho_0.png
    http://radiopaedia.org/articles/rachitic-rosary
  3. Fractures of different ages
  4. Rachitic rosary (prominence of the costochondral junctions) and chest deformities 
    rachitic.rosary.jpg
    http://radiopaedia.org/articles/rachitic-rosary

 

Differential diagnosis

  1. Vitamin D resistant rickets-hypophosphatemia.  Kidney disease leads to phosphate wasting and disruption of calcium and phosphate homeostasis.
  2. Vitamin D dependent rickets- failure to convert 25 OH to 1,25 diOH.  Autosomal recessive.
  3. Renal osteodystrophy- decrease 1 alpha hydroxlase activity in the kidney
  4. Renal tubular acidosis
  5. Malabsorption syndromes
  6. Prematurity

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Treatment

  1. If the serum Ca++ is low, need to give to bring levels up to normal. 10-20 mg of elemental Ca, usually given as 1-2 mL/kg of calcium gluconate, becomes necessary in the case of active tetany or convulsions.
  2. Vitamin D - 300,000 units IM This is a safe and effective method of treating Vit D deficiency and overcomes any issues of compliance. 
  3. Maintenance: 400 units daily orally of Vit D.
    • Per a study conducted in 2010, only 28-35% of infants met this recommendation
  4. Follow up: calcium, phosphorous, and ALP levels 1 month after initiating therapy.
    • Add Radiographs, Mg, 25-OHD, and PTH levels at the 3-month visit
    • Some studies have shown utility in routine monitoring, especially in non-hispanic black populations, females, and overweight patients.
  5. Prevention: Current AAP recommendations include keeping infants < 6 months out of direct sunlight, however, the effect of using sunlight for dark-skinned patients at high/low latitudes have yet to be studied. 

 

References

  1. Greer, F.R. (2009). Defining vitamin D deficiency in children: beyond the 25-OH vitamin D serum concentrations. Pediatrics, 124(5), 1471-1473. 
  2. Misra, M., et. al. (2008). Vitamin D deficiency in children and its management: review of current knowledge and recommendations.  Pediatrics, 122(2), 398-417.
  3. Perrine, C.J., et. al. (2010). Adherence to vitamin D recommendations among US infants. Pediatrics, 125(4), 627-632.
  4. Pupillo, J. (2008). Bone up on new vitamin D recommendations: all infants, children, and adolescents should get at least 400 IU a dayAAP News, 29(10), 1.
  5. Saintonge, S., et. al. (2009). Implications of a new definition of vitamin D deficiency in a multiracial US adolescent population: the national health and nutrition examination survey IIIPediatrics, 123(3), 797-803.
  6. Spence, J.T and Serwint, J.R. (2004). Secondary prevention of vitamin D deficiency rickets. Pediatrics, 113(1), 70-72. 
  7. Wagner, C.L. and Greer, F.R. (2008). Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics, 122(5), 1142-1152.