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I. DEFINITION

Prematurity affects bone mineralization and bone mineral content (BMC). Metabolic bone disease (MBD) of prematurity is a term currently used more often compared with osteopenia of prematurity. MBD is best defined as a decrease in BMC relative to expected level of mineralization for gestational age (GA) with biochemical and radiologic features. Normal bone is formed by the deposition of minerals, predominantly calcium (Ca2+) 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 or MBD is principally a result of inadequate Ca2+ and P intake to meet bone growth demands. Rickets, however, is principally due to vitamin D deficiency; vitamin D supplementation alone will not resolve either osteopenia or rickets. Both disease processes involve the utilization of Ca2+, P, 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. Bone mineral density is the amount of minerals per square centimeter of bone (measured as T-scores [the number of standard deviations (SDs) above or below the mean of a healthy adult of the same sex] or Z-scores [the number of SDs above or below the mean compared with someone with the same age, gender, weight, and ethnicity]). Osteopenia is defined as bone density with as a score of –1 to –2.5.

  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 BMC are both decreased.

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

II. INCIDENCE

The current incidence of MBD in very low birthweight (VLBW; <1500 g) infants is unknown because there is no universal consensus on its definition and no large population-based or network-based studies have addressed this issue. However, due to improvements in nutritional management such as initiation of early feedings, changes in nutritional formulas, and initiation of early parenteral nutrition, the current incidence of MBD may be decreasing. MBD is now more commonly seen in extremely low birthweight (ELBW; <1000 g) infants and those with chronic illnesses such as bronchopulmonary dysplasia/chronic lung disease and necrotizing enterocolitis.

Previous studies have reported osteopenia to occur in 23% of VLBW infants and in 55% to 60% of ELBW infants. A more recent prospective study found mild MBD (alkaline phosphatase [ALP] >500 IU/L and P ≥4.5 mg/dL) in 13.7% and severe MBD (ALP >500 IU/L and P <4.5 mg/dL) in 3.3% of VLBW infants. Fractures have been reported previously in up to 10% of VLBW infants but are likely to be less common now. A recent multicenter retrospective study from England found evidence of rib fractures in approximately 2% of ex-preterm infants (median GA at birth, 26 weeks; median corrected GA at time of chest radiograph, 39 weeks).

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 matrix without the cartilaginous precursors (skull, maxilla, mandible). Several vitamins (A, C, D), cytokines, minerals (Ca2+, P), and hormones (thyroid hormone, estrogen, calcitonin, growth hormone, parathyroid hormone [PTH]–related peptide) play important roles in fetal bone growth. The placenta is essential to ...

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