Bone Metabolism in Children Recovering from Burn Injury

我们以前发现，在从大约40%TBSA的烧伤中恢复的儿童中，骨代谢紊乱导致骨矿物质密度（BMD）的长期不足，这将导致峰值骨量降低并增加后期骨折的风险。骨转换的间接指标的测量表明，骨蛋白和矿物质吸收以及骨重建的紊乱，这些都是骨生长的重要过程。然而，这些过程没有直接的动力学测量。我们的一般假设是，除非骨胶原合成正常，否则不可能发生足够的骨生长和矿化，并且在烧伤儿童中，这些过程减慢或停止。为了验证这一点，我们将使用非放射性、稳定同位素示踪方法来检查骨矿物质转换和胶原蛋白合成。我们将使用~（42）Ca和~（44）Ca来探测骨生长和骨吸收，使用~（13）C和~（15）N脯氨酸（用于新的泛液剂量方案）来测定胶原合成，这在以前从未应用于儿童骨的研究。 我们将开始我们的研究，通过比较从严重烧伤中恢复的儿童和在入院接受择期骨科重建手术期间研究的正常儿童之间的骨代谢、组成和组织形态计量学差异，这些疾病（例如硬化症）不太可能对骨代谢产生重大影响。预测是，在烧伤儿童中，骨合成和骨钙周转受到抑制，这些特征与骨胶原和矿物质代谢的间接指标（例如血清C末端1型（I）前胶原肽、骨钙素）的测量相关。甲状旁腺激素和尿脱氧吡啶啉排泄）。获得这些基线信息后，我们打算测试三种治疗干预措施（即生长激素给药、参与负重运动计划和酮康唑给药抑制皮质醇分泌）。这些结果不仅将为以前烧伤儿童骨骼生长受损的机制提供见解，而且还将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质减少和成人骨质疏松症的潜在病理学。

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.