Osteopenia (Metabolic Bone Disease) of Prematurity
Steven A. Abrams
I. GENERAL PRINCIPLES
A. Definition
Osteopenia is defined as postnatal bone mineralization that is inadequate to fully mineralize bones. Osteopenia occurs commonly in very low birth weight (VLBW) infants. Prior to the use of high-mineral containing diets for premature infants, which is the current practice, significant radiographic changes were seen in about half of the infants with birth weight <1,000 g.
The current incidence is unknown and is likely closely associated with the severity of overall illness and the degree of prematurity. It may still be seen in as many as half of all infants with birth weight <600 g.
Etiology
Deficiency of calcium and phosphorus are the principal causes. Demands for rapid growth in the third trimester are met by intrauterine mineral accretion rates of approximately 120 mg of calcium and 60 mg of phosphorus/kg/day. Poor mineral intake and absorption after birth result in undermineralized new and remodeled bone.
Diets low in mineral content. These diets predispose preterm newborns to metabolic bone disease.
Unsupplemented human milk. In this circumstance, urinary calcium increases, suggesting a phosphorus deficiency that is greater than the calcium deficiency.
Excessive fluid restriction. This may lead to low mineral intake.
Long-term use of parenteral nutrition.
Formulas that are not designed for use in preterm infants (e.g., full-term, elemental, soy-based, lactose-free). Soy-based formulas should be avoided after hospital discharge as well.
Furosemide therapy. This causes renal calcium wasting, but is not likely the principal contributor to osteopenia for most preterm infants.
Long-term steroid use.
Vitamin D deficiency. In mothers not supplemented with high amounts of vitamin D (e.g., >4,000 IU/day), human milk has a total vitamin D content of 25 to 50 IU/L, which is insufficient for maintaining 25-hydroxyvitamin D (25[OH]D) levels in preterm infants at >20 ng/mL. However, when vitamin D intake is adequate, even VLBW newborns can synthesize 1,25-dihydroxyvitamin D (1, 25[OH]2D), although synthesis may be minimal in the first few weeks of life.
Maternal vitamin D deficiency can cause congenital rickets (uncommon) or hypocalcemia (more common).
Inadequate vitamin D intake or absorption produces nutritional rickets, but this is not the primary cause of osteopenia or rickets in preterm infants.
Vitamin D malabsorption and inadequate conversion of vitamin D to 25(OH)D can worsen osteopenia in infants with cholestatic liver disease.
Chronic renal failure (renal osteodystrophy).
Chronic use of phenytoin or phénobarbital increases 25(OH)D metabolism.
Hereditary pseudovitamin D deficiency: type I (abnormality or absence of 1-α-hydroxylase activity) or type II (tissue resistance to 1,25[OH]2D). These are extremely rare.
II. DIAGNOSIS
Clinical presentation
Osteopenia (characterized by bones that are undermineralized or “washed out”) develops during the first postnatal weeks. Signs of rickets (epiphyseal dysplasia and skeletal deformities) usually become evident after 6 weeks postnatal age or by term-corrected gestational age. The risk of bone disease is greatest for the sickest, most premature infants.
History
A history of VLBW, especially <26 weeks or 800 g birth weight, and use of fluid restriction, prolonged parenteral nutrition, or long-term steroid are very common.
Rapid increase in alkaline phosphatase value is common.
A history of a fracture noticed by caregivers or incidentally on x-rays taken for other purposes may be seen.
Physical examination
