In a longitudinal study of 25 preterm infants, we have examined the relationship of bone-specific alkaline phosphatase (ALP), C-terminal propeptide of type I collagen (PICP), N-terminal propeptide of type III procollagen (P3NP), C-terminal telopeptide of type I collagen, urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), with rates of gain in weight, length, and lower leg length and with bone mineral content (BMC), all measured at weekly intervals over the first 10 wk of life. Concentrations of all collagen markers were 10-fold higher than in older children. Each marker showed a distinctive pattern of postnatal change, with early increases in PICP and P3NP and decreases in ICTP reflecting postnatal growth. Once markers had reached a plateau during weeks 4-10, P3NP was positively correlated, whereas Pyd and Dpd were negatively correlated with rate of weight gain (r = +0.44, -0.46, and -0.40, respectively, p < 0.05). P3NP was also positively correlated with overall linear growth (r = +0.44, p < 0.05). PICP was strongly correlated with mean BMC (r = +0.63,p < 0.01) and with total BMC attained by the end of the study period (r = +0.81, p < 0.001). Bone ALP was positively correlated with the rate of bone mineral accretion (r = +0.55, p = 0.01). We conclude that the marker of soft-tissue collagen formation, P3NP, is a good marker for overall ponderal and linear growth in preterm infants, whereas the markers of collagen breakdown, Pyd and Dpd, have inverse relationships with weight gain. The osteoblast markers, PICP and bone ALP, seem to be good surrogate markers for bone mineralization in preterm infants. Markers may provide information on whole-body turnover of bone and collagen that is complementary to traditional physical measures of growth and bone mineralization.

Dexamethasone is used commonly in the treatment of chronic lung disease of prematurity, but there are concerns about possible deleterious effects on growth and bone. Our aim in this study was to examine the effects of dexamethasone treatment on bone and collagen turnover in preterm infants. Bone-specific alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP, reflecting whole-body type I collagen synthesis), and the Nterminal propeptide of type III procollagen (P3NP, reflecting soft tissue collagen turnover), together with the C-terminal telopeptide of type I collagen (ICTP), urinary pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown) were measured at weekly intervals over the first 12 wk of life in 14 preterm infants with chronic lung disease treated with dexamethasone. Results were expressed as SD scores relative to preterm control infants not treated with dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (Ϫ2.1 to Ϫ3.7 SD scores) during the first week of treatment (p Ͻ 0.001), returning to pretreatment levels after stopping dexamethasone. In the group as a whole, these collagen markers were negatively correlated with dexamethasone dose (p Ͻ 0.0001); negative correlations were also seen in most individual babies, although the slopes of individual regression lines varied by a factor of 2. Weight gain at 12 wk was correlated with PICP, expressed as the mean SD score over 12 wk for each baby, (r ϭ 0.69, p Ͻ 0.01) but not with other markers or cumulative dose of dexamethasone. We conclude that dexamethasone markedly suppressed collagen turnover in preterm infants in a dose-dependent fashion, although some babies were more affected than others. The degree of suppression of type I collagen synthesis was a strong independent predictor of overall weight gain over the first 12 wk of life. Steroids are used commonly in the management of preterm infants with developing chronic lung disease (CLD). Dexamethasone has been shown to improve pulmonary compliance and help to wean infants from the ventilator, but there are concerns about side effects (1-3). Glucocorticoids impair growth and bone formation in children (4 -8). We and others have demonstrated that infants treated with dexamethasone have short-term reductions in linear growth, weight velocity, radial length velocity, and bone mineralization compared with those not so treated (9 -11). We have also demonstrated that these infants have reduced calcium absorption and retention, and reduced phosphate retention, compared with infants who did not receive steroids (11).Biochemical markers of bone and soft tissue turnover may give insight into the dynamic effects of therapeutic interventions on bone and growth (12). For the present study, we chose a panel of markers that would reflect various aspects of bone and soft tissue turnover and that have already been validated as markers of growth in older children and as markers of bone formation and resorption by histomorphometry and calcium kinetic studies in adults (1...

Three studies to evaluate procollagen type I C-terminal propeptide, type I collagen cross-linked telopeptide and bone alkaline phosphatase (BALP) in the assessment of bone turnover and growth in children are presented. (1) In 50 short normal children treated with placebo or growth hormone, ΔBALP after 3 months of treatment was highly correlated with height velocity response after 1 year (r = 0.67, p < 0.0001). (2) In 12 children with acute lymphoblastic leukaemia, marked changes in collagen peptides, BALP, and lower leg length velocity were seen during the first 6 months of chemotherapy. Suppression occurred during induction and the two intensification phases, with catch-up during the intervening phase (paired t-tests, p < 0.001). (3) Fourteen babies (birthweight < 1,500 g) treated with high-dose dexamethasone for bronchopulmonary dysplasia were compared with 25 non-steroid-treated babies < 1,500 g. Both collagen peptides decreased rapidly and dramatically (mean decreases 41-68%) after dexamethasone was started, accompanied by weight loss and lower leg shrinkage and followed by recovery during steroid weaning.

Conclusion:While policies focused on uDCD may increase overall DD rates, increases in DD from policies that focus on cDCD come at the expense of DBD. We conclude that cDCD negatively impacts the number of donations from brain dead donors and may lead to an overall reduction in the number of transplants performed due to reduced organ retrieval rates. 2546A Phase 1b, Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Single-Dose, Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of ASKP1240 in de novo Kidney Transplantation