School of Medicine, Physiology Department, Marmara University, Istanbul, Turkey.
School of Medicine, Histology & Embryology Department, Marmara University, Istanbul, Turkey.
Cell Biochem Funct. 2019 Mar;37(2):102-112. doi: 10.1002/cbf.3379. Epub 2019 Feb 27.
The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. HIGHLIGHTS: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.
抗分解代谢双膦酸盐阿仑膦酸钠被认为是绝经后骨质疏松症的一线治疗药物;但它的使用与一些副作用有关，包括胃黏膜损伤。目的是阐明褪黑素联合阿仑膦酸钠治疗是否更有利于维持骨量和预防胃副作用。在麻醉下，雌性 Sprague-Dawley 大鼠行双侧卵巢切除术（OVX），对照组行假手术。手术后 4 周，OVX 大鼠用生理盐水、褪黑素（25μg/ml/d）、阿仑膦酸钠（70μg/kg/wk）、褪黑素+阿仑膦酸钠、褪黑素+褪黑素受体拮抗剂（luzindole，10μg/kg/d）或阿仑膦酸钠+褪黑素+luzindole 治疗 8 周。第 12 周末处死大鼠。检测胫骨中 Runx2 表达、凋亡细胞和小梁厚度，分析胃组织氧化损伤参数。在所有 OVX 组中，Runx2 表达均受抑制。与褪黑素或阿仑膦酸钠治疗组相比，生理盐水处理的 OVX 组钙化面积明显减少，而阿仑膦酸钠+褪黑素治疗组的骨与假手术组相似。组织学检查发现骨组织改善的同时，阿仑膦酸钠或褪黑素治疗组定量 TUNEL（+）细胞也相似减少。生理盐水或阿仑膦酸钠治疗组的胃氧化损伤增加，而褪黑素存在时则减轻。虽然褪黑素和阿仑膦酸钠对维持骨量有相似的支持作用，但褪黑素可能通过预防阿仑膦酸钠引起的胃损伤具有更有利的影响，而阿仑膦酸钠的使用会加重这种损伤。重点：我们的结果表明，阿仑膦酸钠和褪黑素对维持骨量有相似的支持作用，而褪黑素可以预防阿仑膦酸钠的胃副作用，这种联合治疗方法可能是治疗绝经后骨质疏松症的一种可行的治疗方法。
