Bone Metabolism in Children Recovering from Burn Injury

我们之前发现，在大约40% TBSA烧伤后恢复的儿童中，骨代谢紊乱导致骨矿物质密度（BMD）的长期缺陷，这将导致峰值骨量下降，并增加后期骨折的风险。测量骨转换的间接指标表明骨蛋白和矿物质合成代谢以及骨重塑受到干扰，这些都是骨生长的重要过程。然而，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，并且在烧伤儿童中这些过程减慢或停止，否则不可能发生足够的骨生长和矿化。为了验证这一点，我们将使用非放射性、稳定的同位素示踪剂方法检查骨矿物质的转换和胶原蛋白的合成。我们将使用42Ca和44ca来探测骨的增生和吸收，13C和15N脯氨酸（应用于一种新的洪水剂量方案）用于胶原合成的测定，这在以前从未应用于儿童骨骼的研究中。我们将开始我们的研究，比较从严重烧伤中恢复的儿童和接受选择性骨科重建手术的正常儿童在骨代谢、组成和组织形态学方面的差异，因为病情（如硬化症）不太可能对骨代谢产生重大影响。我们预测，烧伤儿童的骨合成和骨钙转换受到抑制，这些特征与骨胶原蛋白和矿物质代谢的间接指标（如血清C-末端1型(I)前胶原肽、骨钙素）的测量有关。甲状旁腺激素和尿脱氧吡啶啉排泄)。在获得这些基线信息后，我们打算测试三种治疗干预措施（即生长激素管理，参与负重运动计划，酮康唑管理抑制皮质醇分泌）。该结果不仅将提供对先前烧伤儿童骨骼生长受损机制的见解，而且还应有助于确定新的治疗靶点；他们可能会对康复计划的设计和实施产生影响。此外，新知识可以帮助我们了解儿童骨质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.