Departament of Geology, University of Oviedo, C/Jesús Arias de Velasco, s/n, 33005, Oviedo, Spain.
Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina.
Biol Trace Elem Res. 2018 Dec;186(2):457-466. doi: 10.1007/s12011-018-1322-1. Epub 2018 Apr 5.
Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics. Young male Wistar rats (half non-diabetic, half with streptozotocin/nicotinamide-induced diabetes) were either untreated or orally administered 625 mg/kg/day of SrR for 6 weeks. After sacrifice, femora from all animals were evaluated by a multi-scale approach (X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical-emission spectrometry, static histomorphometry, pQCT, and mechanical testing) to determine chemical, crystalline, and biomechanical properties. Untreated diabetic animals (versus untreated non-diabetic) showed a decrease in femoral mineral carbonate content, in cortical thickness and BMC, in trabecular osteocyte density, in maximum load supported at rupture and at yield point, and in overall toughness at mid-shaft. Treatment of diabetic animals with SrR further affected several parameters of bone (some already impaired by diabetes): crystallinity index (indicating less mature apatite crystals); trabecular area, BMC, and vBMD; maximum load at yield point; and structural elastic rigidity. However, SrR was also able to prevent the diabetes-induced decreases in trabecular osteocyte density (completely) and in bone ultimate strength at rupture (partially). Our results indicate that SrR treatment can partially but significantly prevent some bone structural mechanical properties as previously affected by diabetes, but not others (which may even be worsened).
长期糖尿病可导致低骨量和骨质疏松症、低压力性骨折发生率增加，和/或骨折愈合延迟。雷奈酸锶（SrR）是一种双重作用的抗骨质疏松药物，其在糖尿病性骨病患者中的应用尚未得到充分评估。在这项研究中，我们研究了 SrR 口服治疗和/或实验性糖尿病对骨成分和生物力学的影响。年轻雄性 Wistar 大鼠（一半非糖尿病，一半链脲佐菌素/烟酰胺诱导的糖尿病）未治疗或口服 625mg/kg/天 SrR 治疗 6 周。处死所有动物后，采用多尺度方法（X 射线衍射、傅里叶变换红外光谱、电感耦合等离子体发射光谱、静态组织形态计量学、pQCT 和机械测试）评估股骨的化学成分、晶体和生物力学特性。与未治疗的非糖尿病动物相比，未治疗的糖尿病动物的股骨矿物质碳酸盐含量、皮质厚度和 BMC、小梁骨细胞密度、破裂和屈服点时的最大负载、以及中轴的整体韧性均降低。用 SrR 治疗糖尿病动物进一步影响了几个骨参数（一些已经因糖尿病而受损）：结晶度指数（表明更不成熟的磷灰石晶体）；小梁面积、BMC 和 vBMD；屈服点时的最大负载；和结构弹性刚性。然而，SrR 还能够完全预防糖尿病引起的小梁骨细胞密度降低（完全）和骨折最终破裂强度降低（部分）。我们的结果表明，SrR 治疗可以部分但显著预防糖尿病先前影响的一些骨结构力学特性，但不能预防其他特性（甚至可能恶化）。
