The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n ϭ 8/group): 1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d; 2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p Ͻ 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p Ͻ 0.05). The significant weight reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction. Abbreviations BMC, bone mineral content Cr, creatinine CV, coefficient of variation DEX, dexamethasone NTx, N-terminal telopeptide of type I collagen VLBW, very low birth weight VLBW infants may develop severely compromised lung function because of their immaturity. The incidence of bronchopulmonary dysplasia in VLBW infants has been reported to be as high as 70% (1). DEX is prescribed for these infants to improve pulmonary compliance and to facilitate earlier weaning from the ventilator (2, 3). However, linear, weight and bone growth can be adversely affected by DEX administration in VLBW infants (4 -7). Despite these side effects, DEX continues to be used in treatment of chronic lung disease (8 -10). Although both tapered (3-6) and constant (8) dosing regimens are used in clinical practice, it is not known whether they induce similar restrictions in growth and bone development.The rapidly growing piglet is a good model for human infants (11). From our experience with piglets, monitoring growth for a 2-wk period (12, 13) parallels the changes in weight (4-fold increase) and length (1.2-fold increase) that we observe in VLBW human infants over 8.5 wk or from their birth to term-adjusted age (4). Piglets respond like human infants in the metabolic processing of minerals, and they have been used successfully to measure responses in growth and bone development to alterations in dietary minerals (14), administration of DEX (...