Simha Vinaya, Zerwekh Joseph E, Sakhaee Khashayar, Garg Abhimanyu
Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
J Clin Endocrinol Metab. 2002 Nov;87(11):4942-5. doi: 10.1210/jc.2002-020792.
The adipocyte-derived hormone leptin, which plays an important role in energy homeostasis, has been suggested to have an influence on bone development and remodeling. However, it is not clear from animal studies whether leptin is a stimulator or an inhibitor of bone growth. Cross-sectional studies in humans suggest that serum leptin levels are positively associated with bone mineral density (BMD), but these observations are not consistent, and whether this relationship is independent of obesity remains unclear. We therefore examined the effect of sc leptin administration on BMD and markers of bone turnover in two women, one with congenital generalized lipodystrophy and the other with acquired generalized lipodystrophy. Both patients had regular menstrual cycles. At baseline, the BMD for both patients, measured at the lumbar spine and total hip, was within 1 SD of the peak bone mass. There was no significant change in BMD in both patients after 16-18 months of leptin therapy. Similarly, concentrations of serum osteocalcin and bone-specific alkaline phosphatase or urinary excretion of deoxypyridinoline and N-telopeptides remained unchanged after 6-8 months of leptin therapy, suggesting no effects of leptin on osteoblastic or osteoclastic activity. Our preliminary data suggest that sc leptin replacement in hypoleptinemic patients with generalized lipodystrophy has no effect on the mature adult skeleton.
脂肪细胞分泌的激素瘦素在能量平衡中起重要作用，有人认为它对骨骼发育和重塑有影响。然而，从动物研究中尚不清楚瘦素是骨骼生长的刺激物还是抑制剂。对人类的横断面研究表明，血清瘦素水平与骨矿物质密度（BMD）呈正相关，但这些观察结果并不一致，而且这种关系是否独立于肥胖尚不清楚。因此，我们研究了皮下注射瘦素对两名女性骨矿物质密度和骨转换标志物的影响，一名患有先天性全身性脂肪营养不良，另一名患有获得性全身性脂肪营养不良。两名患者月经周期均规律。基线时，两名患者腰椎和全髋部测量的骨矿物质密度均在峰值骨量的1个标准差范围内。瘦素治疗16 - 18个月后，两名患者的骨矿物质密度均无显著变化。同样，瘦素治疗6 - 8个月后，血清骨钙素和骨特异性碱性磷酸酶浓度或脱氧吡啶啉和N - 端肽的尿排泄量均保持不变，表明瘦素对成骨细胞或破骨细胞活性无影响。我们的初步数据表明，在患有全身性脂肪营养不良的低瘦素血症患者中皮下注射瘦素替代治疗对成熟的成年骨骼没有影响。
