116: Osteopenia of Prematurity

I. DEFINITION

Prematurity affects bone mineralization and bone growth—thus the entity known as osteopenia of prematurity; however, some authors use the term “rickets of prematurity.” Normal bone is formed by the deposition of minerals, predominantly calcium (Ca⁺²) and phosphorus (P), onto an organic matrix (osteoid) secreted by the osteoblasts. Osteoclasts play an important role in bone resorption and remodeling. Although osteopenia and rickets result in decreased bone mineralization and may have similar clinical findings, they are not identical processes and thus the term “rickets of prematurity” is not used in this chapter. Osteopenia of prematurity is principally a result of inadequate calcium intake to meet bone growth demands. Rickets, however, is principally due to vitamin D deficiency, but vitamin D supplementation alone will not resolve either osteopenia or rickets. Both disease processes involve the utilization of calcium, phosphorous, and vitamin D.

1. Osteopenia. Refers to a decrease in the amount of organic bone matrix (osteoid) due to a decrease in the thickness or number of trabeculae and/or decreased thickness of the bone cortex. These can be due to either insufficient deposition or increased resorption of the organic bone matrix.

2. Osteomalacia. Refers to the lack of mineralization of the organic bone matrix resulting in accumulation of nonmineralized osteoid and softening of bones. When involving the growth plate, it results in rickets. Bone density and bone mineral content (BMC) are both decreased.

3. Osteoporosis. Refers to a decrease in bone mineral density <2.5 standard deviations from the norm (adults). There is no accepted definition of osteoporosis in infants.

II. INCIDENCE

Due to improvements in nutritional management such as initiation of early feedings, changes in nutritional formulas, and other clinical practices such as initiation of early parenteral nutrition, the current incidence of osteopenia is difficult to estimate. It is now more commonly seen in extreme prematurity and preterm infants with chronic illnesses such as bronchopulmonary dysplasia/chronic lung disease and necrotizing enterocolitis.

Previously, osteopenia has been reported in 23% of very low birthweight infants (VLBW) and in 55–60% of extremely low birthweight infants <1000 g. It was more commonly reported in breast-fed (40%) compared with formula-fed (16%) infants. Fractures have been reported in up to 10% of VLBW infants but are likely to be less common now.

III. PATHOPHYSIOLOGY

Intrauterine bone formation occurs either as endochondral ossification (axial and appendicular skeleton) with the deposition of an osteoid matrix with a cartilaginous core or as membranous without the cartilaginous precursors (skull, maxilla, mandible). Several vitamins (A, C, D), cytokines, minerals (calcium), and hormones (thyroid hormone, growth hormone, parathyroid hormone related peptide) play important roles in fetal bone growth. The placenta is essential to fetal nutrient and mineral accretion.

1. An increase in trabecular thickness and bone volume occurs faster in utero compared with ex utero. After birth, bone growth ...