Topic updated on 08/08/16 12:21pm
  • A defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate
    • prior to closure of physis known as rickets
    • after physeal closure called osteomalacia
  • Pathophysiology
    • disruption of calcium/phosphate homeostasis
    • poor calcification of cartilage matrix of growing long bones
    • occurs at zone of provisional calcification
    • leads to increased physeal width and cortical thinning and bowing
    • Vitamin D and PTH  play an important role in calcium homeostasis 
  • Associated conditions
    • orthopaedic manifestations include
      • brittle bones with physeal cupping/widening
      • bowing of long bones 
      • ligamentous laxity
      • flattening of skull
      • enlargement of costal cartilage (rachitic rosary) 
      • kyphosis (cat back) 
  • Types include 
    • familial hypophosphatemic (vitamin D-resistant) (see below)
    • vitamin D-deficient (Nutritional)
    • vitamin D-dependent (type I & type II)
    • renal osteodystrophy 
    • hypophosphatasia 
  • Radiographs 
    • recommended views
      • AP and lateral of affected bone
    • findings
      • physeal widening
      • metaphyseal cupping
      • Looser's zones (pseudofracture on the compression side of bone)
      • decreased bone density
      • prominence of rib heads at the osteochondral junction (rachitic rosary)
      • bowing (often genu varum
  • Laboratory studies
  •  Histology 
    • zone of proliferation is disordered and elongated in growthplate
    • widened osteoid seams
    • swiss cheese trabeculae
    • poorly defined zone of provisional calcification
Familial Hypophosphatemic Rickets
  • Also known as
    • Vitamin D resistant Rickets
    • X-linked hypophosphatemic
  • Most common form of heritable rickets 
    • caused by inability of renal tubules to absorb phosphate
    • GFR is normal
    • impaired vitamin D3 response
  • Genetics
    • X-linked dominant
  • Presentation
    • tibial bowing as result of widened proximal tibia physis 
  • Labs    
    • low serum phosphorous
    • elevated alkaline phosphatase 
    • serum calcium is usually normal or low normal
  • Treatment
    • medical treatment
      • Calcitriol
        • indications
          •  is standard therapy
      • phosphate replacement
        • indications
          • controversial and counter-intuitive
          • physiology would suggest that phosphate replacement would be beneficial and treatment of 1-3 grams phosphate daily was recommended
          • recent research evaluated the addition of phosphate to the standard vitamin D therapy and found no additional benefit with phosphate therapy
    • surgical treatment
      • corrective surgery
        • indications
          • to correct tibial bowing in severe deformity
Vitamin D-Deficiency Rickets (Nutritional)
  • Nutritional rickets is associated with decreased dietary intake of Vitamin D
    • rare now that Vitamin D is added to milk
    • still seen in 
      • premature infants
      • patients with malabsorption syndromes (celiac sprue) or chronic parenteral nutrition
      • Asian immigrants
      • Patients with out of the ordinary dietary choices
  • Physiology
    • low Vitamin D levels lead to decreased intestinal absorption of calcium
    • low calcium levels leads to a compensatory increase in PTH and bone resorption
    • bone resorption leads to increased alkaline phosphatase levels
  • Clinical findings 
    • rachitic rosary (enlargement of costochondral junction)
    • bowing of knees
    • codfish vertebrae 
    • retarded bone growth (widened osteoid seams, physeal cupping) 
    • muscle hypotonia
    • dental disease
    • pathologic fractures
    • waddling gate
  • Laboratory values 
    • low to normal serum calcium
    • low serum phosphate
    • elevated alkaline phosphatase
    • elevated parathyroid hormone
    • low vitamin D
  • Treatment
    • Vitamin D (5000 IU daily)
      • indications
        • resolves most deformities
Hereditary Vitamin D-Dependent Rickets (Type I and II)
  • Rare disorder 
  • Clinical features similar to Vitamin D-Deficient Rickets but more severe 
  • Clinical characteristics
    • Type I
      • joint pain/deformity, hypotonia, muscle weakness, growth failure, and hypocalcemic seizures or fractures in early infancy
    • Type II
      • bone pain, muscle weakness, hypotonia, hypocalcemic convulsions, growth retardation, severe dental caries or teeth hypoplasia
  • Pathophysiology     
    • Type I 
      • caused by defect in renal 25-(OH)-vitamin D1 alpha-hydroxylase 
        • prevents conversion of inactive form of vitamin D to active form
      • responsible gene 12q14
    • Type II 
      • caused by a defect in intracellular receptor for 1,25-(OH)2-vitamin D
  • Genetics
    • type II                         
      • autosomal recessive
  • Laboratory values
    • type II is distinguished from type I by markedly elevated levels of 1,25-(OH)2-Vitamin D
  • Treatment
    • physiologic doses (1-2 micrograms/day) of 1,25-(OH)2-Vit D
      • indications
        • type I 
    • daily high dose Vitamin D + elemental calcium
      • indications
        • type II


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Qbank (8 Questions)

(OBQ13.38) Low serum phosphate and normal calcium levels are found in what common etiology of hereditary rickets? Topic Review Topic

1. X-linked hypophosphatemic
2. Vitamin D-dependent, type I
3. Vitamin D-dependent, type II
4. Autosomal dominant hypophosphatemic
5. Jansen's metaphyseal chondrodysplasia

(OBQ10.55) Laboratory values of a normal serum calcium and parathyroid hormone can be found in which of the following disease states? Topic Review Topic

1. Primary hyperparathyroidism
2. Type I vitamin D deficient rickets
3. Type II vitamin D deficient rickets
4. X-linked hypophosphatemic rickets
5. Nutritional rickets

(OBQ09.117) You are seeing a 4-year-old girl for leg deformities on a mission trip to Haiti. Clinical photograph and radiographs of her lower extremities and wrist are shown in Figures A-C. What laboratory studies would help confirm a nutritional deficiency as opposed to an X-linked genetic disorder as a cause of her condition? Topic Review Topic
FIGURES: A   B   C      

1. Low serum phosphate, elevated alkaline phosphatase, elevated PTH
2. Low serum phosphate, elevated alkaline phosphatase, normal PTH
3. Low serum phosphate, elevated alkaline phosphatase, decreased PTH
4. Elevated serum phosphate, elevated alkaline phosphatase, elevated PTH
5. Elevated serum phosphate, decreased alkaline phosphatase, decreased PTH

(OBQ08.121) Loss of function in the 25(OH) vitamin D1-alpha hydroxylase gene causes which of the following diseases? Topic Review Topic

1. Hyperphosphatemia
2. Vitamin D resistant rickets
3. Hereditary Vitamin D dependant rickets type I
4. Hereditary Vitamin D dependant rickets type II
5. Hypophosphatemic rickets

(OBQ07.271) Which of the following laboratory values would be consistent with nutritional rickets? Topic Review Topic

1. increased calcium level
2. increased phosphate level
3. decreased alkaline phosphatase level
4. increased vitamin D level
5. increased parathyroid hormone level

(OBQ04.95) The active form of vitamin-D (calcitriol) is produced by the enzyme 1-alpha-hydroxylase. What hormone activates this enzyme? Topic Review Topic

1. thyroid stimulating hormone (TSH)
2. parathyroid hormone (PTH)
3. estrogen
4. progesterone
5. testosterone

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