Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan.
Clinical Development Center, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan.
Endocrinology. 2019 Oct 1;160(10):2339-2352. doi: 10.1210/en.2019-00239.
Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.
骨质疏松症是糖尿病(DM)的并发症。糖尿病性骨质疏松症的病理与绝经后骨质疏松症不同,且没有针对糖尿病性骨质疏松症的特定治疗指南。在目前的研究中,通过评估骨质疏松症药物(如合成代谢剂 PTH[特立帕肽(TPTD)]和抗吸收剂降钙素[依降钙素(ECT)]和双膦酸盐[利塞膦酸钠(RIS)])对骨代谢以及对自发性糖尿病 Torii(SDT)肥胖大鼠(2 型糖尿病(T2DM)的模型)的葡萄糖和脂质代谢的影响,解决了这个问题。这些药物每周三次皮下注射到 8 周龄雄性 SDT 肥胖大鼠体内,共 8 周。在 SDT 肥胖大鼠中,TPTD 治疗可增加椎骨小梁骨上的成骨细胞数量和功能,并增加小梁骨量、骨密度(BMD)和椎骨的机械强度。此外,TPTD 可改善皮质骨结构并增加 BMD。RIS 减少了破骨细胞数量和功能,导致股骨骨干的椎体骨矿物质含量和 BMD 增加,并且椎骨的机械强度增加。ECT 对骨量或代谢没有明显影响。与糖尿病病变相似,所有药物对高血糖、胰腺形态或血清胰岛素和胰高血糖素水平均无影响。然而,TPTD 组的甘油三酯水平和脂肪肝中的脂质滴减少。这些结果表明,TPTD 除了可用于治疗 T2DM 中的骨质疏松症外,还可能对治疗脂肪肝有用。