Nutritional rickets

Nutritional rickets (see Table 1.16)

• Vitamin D–deficiency rickets

  • Rare after addition of vitamin D to milk, except in the following populations:

    • Asian immigrants

    • Patients with dietary peculiarities

    • Premature infants

    • Patients with malabsorption (celiac sprue)

    • Patients receiving long-term parenteral nutrition

  • Decreased intestinal absorption of calcium and phosphate leads to secondary hyperparathyroidism.

  • Laboratory findings

    • Low-normal calcium level (maintained by high PTH level)

    • Low phosphate level (excreted because of the effect of PTH)

    • Increased alkaline phosphatase level

    • Low vitamin D level

    • Increased PTH level leads to higher bone absorption

  • Physical examination

    • Enlargement of the costochondral junction (rachitic rosary)

    • Bowing of the knees

    • Muscle hypotonia

    • Dental disease

    • Pathologic fractures (Looser zones: pseudofractures on the compression sides of bones)

    • Milkman’s fracture

    • Waddling gait

  • Radiographic findings

    • Physeal widening and cupping

    • Coxa vara

    • Codfish vertebrae

    • Retarded bone growth (defect in the hypertrophic zone, widened osteoid seams)

  • In affected children, height is commonly below the fifth percentile for age.

  • Treatment with vitamin D (1000–6000 IU daily

    based on weight) resolves most deformities.

• Calcium-deficiency rickets (Fig. 1.19)

• Phosphate-deficiency rickets

Hereditary vitamin D–dependent rickets

• Rare disorders with features similar to those of vitamin D–deficiency (nutritional) rickets, except that symptoms may be worse and patients may have total baldness

  • Type I: defect in renal 25(OH)D 1α-

    hydroxylase, inhibiting conversion of inactive vitamin D to its active form

    • Autosomal recessive inheritance

    • Gene on chromosome 12q14

  • Type II: defect in an intracellular receptor for 1,25(OH)2D3

Familial hypophosphatemic rickets (vitamin D–resistant rickets or phosphate diabetes)

Most commonly encountered form of rickets

• X-linked dominant inheritance

   

   

   

  FIG. 1.19 Nutritional calcium deficiency.

  From Netter FH: CIBA collection of medical illustrations, vol 8: Musculoskeletal system, part I: Anatomy, physiology and developmental disorders, Basel, Switzerland, 1987, CIBA, p 184.

   

Impaired renal tubular reabsorption of phosphate

Normal GFR with an impaired vitamin D3 response

Normal serum calcium, low serum phosphorus and 1, (OH)2D3, and high serum alkaline phosphatase levels

Treatment:

First line treatment with burosumab (anti-FGF23 monoclonal antibody)

Second line elemental phosphate (1–2 g/day plus vitamin D 0.5–1 µg/day)

Hypophosphatasia

• Autosomal recessive

• Error in the tissue-nonspecific isoenzyme of alkaline phosphatase

  • Leads to low levels of alkaline phosphatase, which is required for

    synthesis of inorganic phosphate (Pi) and important in bone matrix formation

• Features are similar to those of rickets.

• Increased urinary phosphoethanolamine is diagnostic.

• Treatment may include phosphate therapy.Table 1.15

   

  Laboratory Findings and Clinical Data Regarding Patients

   

   

  Changes in Level or Concentration
  Disorder Serum Serum Alka Calcium Phosphastase Phos
  Hypopara-thyroidism	↓	↑	Non
  Pseudohypoparathyroidism	↓	↑	Non
  Renal osteodystrophy (high-turnover bone disease resulting from renal disease [secondary hyperparathyroidism])	↓ or none	↑↑↑	↑

  Renal osteodystrophy	↑ or none	None or ↑	↑
  (low-turnover bone
  disease due to renal
  disease [aluminum
  toxicity])

  ↓, Decreased; ↑, increased.

   

   

   

  Table 1.16

   

  Laboratory Findings and Clinical Data Regarding Patients

   

   

  Changes in Level or Concentration
  Disorder Serum Serum Alkaline PTH Calcium Phos phos
  Nutritional rickets: vitamin D deficiency	↓ or none	↓	↑	↑

  Nutritional rickets: calcium deficiency	↓ or none	↓	↑	↑
  Nutritional rickets: phosphate deficiency	None	↓	↑	None
  Hereditary vitamin D–dependent rickets type I (pseudo–vitamin D deficiency)	↓	↓	↑	↑
  Hereditary vitamin D–dependent rickets type II [hereditary resistance to 1,25(OH)2D]	↓	↓	↑	↑
  Hypophosphatemic rickets (also known as vitamin D–resistant rickets and phosphate diabetes; Albright syndrome is an example of a	None	↓↓↓	↑	None

  hypophosphatemic syndrome)
  Hypophosphatasia	↑	↑	↓↓↓	None

  ↓, Decreased; ↑, increased; phos, phosphatase.

   

  Table 1.17

   

  Differential Diagnosis of Metabolic Bone Diseases Based

   

   

  Calcium Level
  Increased	Decreased
  Primary	Hypoparathyroidism Pseudohypoparathyr Renal osteodystrophy (high-turnover bo disease) Nutritional rickets: vi D deficiency Nutritional rickets: ca deficiency Hereditary vitamin D dependent rickets (types I and II) Malignancy with bon metastasis Malignancy without metastasis Multiple myeloma Lymphoma Hyperthyroidism Vitamin D intoxicatio Sarcoidosis Milk-alkali syndrome Severe generalized immobilization
  hyperparathyroidism
  Hyperthyroidism
  Vitamin D intoxication
  Malignancy without bony
  metastasis
  Malignancy with bony
  metastasis
  Multiple myeloma
  Lymphoma
  Sarcoidosis
  Milk-alkali syndrome
  Severe generalized
  immobilization
  Multiple endocrine
  neoplasias
  Addison disease
  Steroid administration
  Peptic ulcer disease
  Hypophosphatasia
  Pseudohypoparathyroidism
  Renal osteodystrophy
  Nutritional rickets: vitamin
  D deficiency
  Nutritional rickets: calcium
  deficiency
  Hereditary vitamin D–
  dependent rickets (types
  I and II)