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.

INTRODUCTION: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.