Bone Metabolism in Children Recovering from Burn Injury

我们先前发现，在烧伤面积约为40%的儿童中，骨代谢紊乱会导致长期的骨密度(BMD)不足，这将导致峰值骨量下降，并增加日后骨折的风险。对骨转换的间接指标的测量表明，骨蛋白质和矿物质合成代谢紊乱，以及骨重建，这些都是骨生长的重要过程。然而，还没有对这些过程进行直接的动力学测量。我们的一般假设是，除非骨胶原合成正常发生，否则不太可能发生足够的骨骼生长和矿化，而烧伤儿童的这些过程会放缓或停止。为了测试这一点，我们将使用非放射性、稳定的同位素示踪方法来检测骨矿物质的周转和胶原的合成。我们将用42Ca和44Ca来探测骨的吸收和吸收，用13C和15N Pro(应用于一种新的洪泛剂量方案)来测定胶原合成，这是以前从未应用于儿童骨骼研究的。我们将通过比较严重烧伤后康复的儿童和入院接受选择性骨科重建手术的正常儿童在骨代谢、成分和组织形态计量学方面的差异开始我们的研究，这些儿童的情况(如硬化症)不太可能对骨代谢产生重大影响。据预测，烧伤儿童的骨合成和骨钙转换受到抑制，这些特征与骨胶原和矿物质代谢的间接指标(如血清C端I型(I)前胶原肽、骨钙素)相关。甲状旁腺激素和尿脱氧吡啶酚排泄)。在获得这一基线信息后，我们打算测试三种治疗干预措施(即生长激素注射，参加负重运动计划，以及酮康唑注射抑制皮质醇分泌)。这些结果不仅将为以前烧伤的儿童损害骨骼生长的机制提供见解，还应该有助于确定新的治疗靶点；它们可能有助于影响康复计划的设计和实施。此外，新的知识可以帮助我们了解儿童骨量减少和成人骨质疏松症的潜在病理。

We previously found that in children recovering from burns of approximately 40% TBSA, disturbances in bone metabolism result in long-term deficits in bone mineral density (BMD) which will result in decreased peak bone mass and increase the risks of later fracture. Measurement of indirect indices of bone turnover suggest disturbances in bone protein and mineral anabolism and also bone remodeling, all important processes in bone growth. However no direct kinetic measurement of these processes have been made. Our general hypothesis is that adequate bone growth and mineralization are unlikely to occur unless bone collagen synthesis occurs normally and that in burned children these processes are slowed or arrested. To test this we will examine bone mineral turnover and collagen synthesis using non- radioactive, stable isotope tracer methodology. We will use 42Ca and 44 Ca, to probe bone accretion and resorption and 13C and 15N proline (applied in a novel flooding dose protocol) for assay of collagen synthesis, which has never before been applied to the study of bone in children. We will begin our studies by comparing differences in bone metabolism, composition and histomorphometry between children recovering from major burn injury and normal children studied during admission for a elective orthopedic reconstructive surgery, for conditions (e.g. sclerosis) unlikely to have a major impact upon bone metabolism. The prediction is that in the burned children bone synthesis and bone calcium turnover are depressed, features which correlate with measures of indirect indices of bone collagen and mineral metabolism (e.g. serum C- terminal Type 1 (I) pro-collagen peptide, osteocalcin. parathyroid hormone and urinary deoxypyridinoline excretion). Having obtained this baseline information we intend to test three therapeutic interventions (i.e. growth hormone administration, participation in a weight-bearing exercise program, and inhibition of cortisol secretion by ketoconazole administration). The results will not only provide insights into the mechanisms impairing bone growth in previously burned children, but should also help to identify new therapeutic targets; they may possibly benefit the influence the design and implementation of rehabilitation programs. Furthermore, the new knowledge could help us understand the underlying pathology involved in osteopenia in children and osteoporosis in adults.