Because the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal and senescence pathology has been considered since long. One relevant melatonin target site in aging individuals is bone where melatonin chronobiotic effects mediated by MT1 and MT2 receptors are demonstrable. Precursors of bone cells located in bone marrow are exposed to high quantities of melatonin and the possibility arises that melatonin acts a cytoprotective compound via an autacoid effect. Proteins that are incorporated into the bone matrix, like procollagen type I c-peptide, augment after melatonin exposure. Melatonin augments osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts. Osteoclasts are target cells for melatonin as they degrade bone partly by generating free radicals. Osteoclast activity and bone resorption are impaired via the free radical scavenger properties of melatonin. The administration of melatonin in chronobiotic doses (less than 10 mg daily) is commonly used in clinical studies on melatonin effect on bone. However, human equivalent doses allometrically derived from animal studies are in the 1–1.5 mg/kg/day range for a 75 kg human adult, a dose rarely used clinically. In view of the absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers, further investigation is needed to determine whether high melatonin doses have higher therapeutic efficacy in preventing bone loss.

中文翻译：

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褪黑激素作为骨骼中的生物钟/细胞保护剂。涉及剂量

由于时间生物和细胞保护分子褪黑激素随着年龄的增长而减少，因此长期以来人们一直认为它与绝经后和衰老病理有关。衰老个体中褪黑激素的一个相关靶位点是骨骼，其中由 MT1 和 MT2 受体介导的褪黑激素的生物钟效应是显而易见的。位于骨髓中的骨细胞前体暴露于大量褪黑激素，并且褪黑激素可能通过自体效应发挥细胞保护化合物的作用。融入骨基质的蛋白质，如 I 型前胶原 C 肽，在暴露于褪黑激素后会增加。褪黑激素可增强骨保护素，这是一种抑制破骨细胞分化的成骨细胞蛋白。破骨细胞是褪黑激素的靶细胞，因为它们部分通过产生自由基来降解骨骼。褪黑激素的自​​由基清除剂特性会损害破骨细胞的活性和骨吸收。在褪黑激素对骨骼影响的临床研究中，通常使用按时间生物剂量（每天少于 10 毫克）施用褪黑激素。然而，从动物研究中异速生长得出的人体等效剂量对于 75 公斤的成人来说在 1–1.5 毫克/公斤/天的范围内，这一剂量在临床上很少使用。鉴于在正常志愿者中剂量高达100 mg的1期药理学研究中未发现褪黑素的毒性，需要进一步研究以确定高剂量褪黑素是否具有更高的预防骨质流失的治疗效果。