We assessed whether systemic Strontium ranelate (SrRan) administration accelerates the healing of a bone defect and could modulate local bone cellular activities. Proximal tibia bone defects were created in 6-month-old female rats, which received then orally SrRan (625 mg/kg per day, 5/7 days) or vehicle (controls) for 4, 8, or 12 weeks. Bone samples were analysed by micro-computed tomography and histomorphometry in various compartments, ie metaphyseal second spongiosa (MC), a region close to the defect (CDC), within the healing defect (DC) and in cortical defect bridging region. All mentioned results are statistically significant.
From 8 weeks of treatment and independently of the site, SrRan decreased bone resorption as indicated by reduced active osteoclast surfaces. In contrast, bone formation was stimulated within DC and CDC at early stage of healing as shown by increased mineral apposition rate (MAR) at endosteal compartment by week 4 and increased bone formation rate in CDC and DC by weeks 8 and 12. Osteoid surface and thickness were not altered in DC, suggesting that osteoblast function was modulated toward mineral apposition rather than differentiation. This is supported by increased adjusted apposition rate and a trend to lower mineralization lag time in early healing phase. This led to an increase in trabecular bone mass by weeks 8 and 12 at each trabecular site investigated in SrRan vs time-matched controls. Cortical defect bridging was detected earlier compared to changes in trabecular compartment and was accelerated in SrRan compared to controls. Increased endosteal MAR in early stage of healing led to higher cortical thickness by week 4 in SrRan vs controls, with a trend to lower periosteal osteoclast surfaces by week 8.
In healing of both trabecular and cortical compartments bone defect, SrRan early stimulated formation and later decreased resorption, suggesting potential advantages in orthopaedic surgery.
17 May 2014 - 20 May 2014