Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital, 4, rue Gabrielle-Perret-Gentil, CH-1211, Geneva 14, Switzerland.
GEROM-LHEA, Institut de Biologie en Santé, University of Angers, Angers, France.
Osteoporos Int. 2017 Dec;28(12):3475-3487. doi: 10.1007/s00198-017-4156-3. Epub 2017 Sep 28.
Strontium ranelate treatment is known to prevent fractures. Here, we showed that strontium ranelate treatment enhances bone healing and affects bone cellular activities differently in intact and healing bone compartments: Bone formation was increased only in healing compartment, while resorption was reduced in healing and normal bone compartments.
Systemic administration of strontium ranelate (SrRan) accelerates the healing of bone defects; however, controversy about its action on bone formation remains. We hypothesize that SrRan could affect bone formation differently in normal mature bone or in the bone healing process.
Proximal tibia bone defects were created in 6-month-old female rats, which orally received SrRan (625 mg/kg/day, 5/7 days) or vehicle (control groups) for 4, 8, or 12 weeks. Bone samples were analyzed by micro-computed tomography and histomorphometry in various regions, i.e., metaphyseal 2nd spongiosa, a region close to the defect, within the healing defect and in cortical defect bridging region. Additionally, we evaluated the quality of the new bone formed by quantitative backscattered electron imaging and by red picosirius histology.
Healing of the bone defect was characterized by a rapid onset of bone formation without cartilage formation. Cortical defect bridging was detected earlier compared with healing of trabecular defect. In the healing zone, SrRan stimulated bone formation early and laterly decreased bone resorption improving the healing of the cortical and trabecular compartment without deleterious effects on bone quality. By contrast, in the metaphyseal compartment, SrRan only decreased bone resorption from week 8 without any change in bone formation, leading to little progressive increase of the metaphyseal trabecular bone volume.
SrRan affects bone formation differently in normal mature bone or in the bone healing process. Despite this selective action, this led to similar increased bone volume in both compartments without deleterious effects on the newly bone-formed quality.
雷奈酸锶治疗已知可预防骨折。在此，我们表明雷奈酸锶治疗可增强骨折愈合，并以不同的方式影响完整骨和愈合骨部位的骨细胞活动：仅在愈合部位增加骨形成，而在愈合和正常骨部位减少骨吸收。
全身给予雷奈酸锶（SrRan）可加速骨缺损的愈合；然而，关于其对骨形成的作用仍存在争议。我们假设 SrRan 可能会以不同的方式影响正常成熟骨或骨愈合过程中的骨形成。
在 6 月龄雌性大鼠的胫骨近端创建骨缺损，这些大鼠口服 SrRan（625mg/kg/天，5/7 天）或载体（对照组）4、8 或 12 周。通过微计算机断层扫描和组织形态计量学在不同区域（即，骺骨 2 级松质骨、靠近缺损的区域、愈合缺损内和皮质缺损桥接区域）分析骨样本。此外，我们通过定量背散射电子成像和红偏光天狼星组织学评估新形成的骨的质量。
骨缺损的愈合表现为快速起始的骨形成，无软骨形成。皮质缺损桥接比小梁缺损愈合更早检测到。在愈合区域，SrRan 早期刺激骨形成，随后骨吸收减少，改善皮质和小梁骨的愈合，而不会对骨质量产生有害影响。相比之下，在骺骨区域，SrRan 仅在第 8 周后减少骨吸收，但骨形成没有任何变化，导致骺骨小梁骨体积的逐渐增加很少。
SrRan 在正常成熟骨或骨愈合过程中以不同的方式影响骨形成。尽管有这种选择性作用，但这导致两个部位的骨体积都有相似的增加，而对新形成的骨质量没有有害影响。
