Strontium Ranelate Treatment Improves Trabecular and Cortical Intrinsic Bone Tissue Quality, a Determinant of Bone Strength

Abstract

Beside its influence on determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality as evaluated by nanoindentation, increasing elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for 104 wk with daily dose from 0 to 900 mg/kg. Introduction:We previously showed that strontium ranelate treatment improves the mechanical properties of the vertebral body and long bone midshaft in intact rats. The increased energy to failure obtained with strontium ranelate is essentially caused by an increase in plastic energy, suggesting that bone formed during treatment can withstand greater deformation before fracture. In the bone mineral phase, strontium is mainly located in the hydrated shell and could thus potentially influence intrinsic bone tissue quality. Materials and Methods: To study whether strontium ranelate treatment could positively influence intrinsic bone tissue quality (elastic modulus, hardness, and dissipated energy), nanoindentation tests were performed at the level of trabecular nodes and cortex under physiological or dry conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a daily dose of 0, 225, 450, or 900 mg/kg (n ‫ס‬ 12 per group). Ex vivo CT measurements and axial compression tests of adjacent vertebral bodies were also performed. Significance of difference was evaluated using ANOVA. Results: In agreement with previous results, strontium ranelate (900 mg/kg/d) significantly increased versus controls in maximal load (+23%), total energy (+71%), and plastic energy (+143%). At the level of trabecular bone, strontium ranelate treatment resulted in a significant increase in elastic modulus (+15.1%, p < 0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001) versus controls in physiological, but not in dry, conditions. The effect was less pronounced in cortex. Conclusions: These results show for the first time a direct action of strontium ranelate on bone tissue quality. Beside its shown influence on classical determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality. This could contribute to the increase in bone strength and thus be involved in the reduction of fracture risk in postmenopausal osteoporotic patients treated with strontium ranelate.

Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor

“…Another factor that strongly affects bone strength is the quality of bone matrix (Ammann et al 2007). Glp1r KO mice presented with a decrease in maximum load (K17%), hardness (K19%), and dissipated energy (K15%).…”

“…Before mechanical testing, the femurs were thawed overnight and rehydrated in saline for 24 h at room temperature as described elsewhere (Ammann et al 2007). Three-point bending strength was measured with a constant span length of 10 mm.…”

A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis

“…In mice, this is reflected in an increase in vertebral bone mass. Studies in rats have demonstrated that in addition to the increase in bone mass, there is an increase in cortical thickness and an improvement in trabecular and cortical microarchitecture, leading to an increased bone quality and strength [Ammann et al 2004[Ammann et al , 2007. In ovariectomized rats, an established animal model for postmenopausal osteoporosis, strontium ranelate was able to prevent bone loss by decreasing bone resorption while maintaining bone formation not only in the short term [Marie et al 1993], but also in the long term [Bain et al 2009].…”

Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model

“…Considering the poor quality and quantity of bone in osteoporosis, there are efforts to enhance fracture healing in this situation. [9][10][11] In treatment of osteoporosis, vitamin D3 (vitD3) and calcium supplementation has been considered a baseline therapy. It has been shown that administration of antiresorptive agents sustains or increases bone mass by suppressing bone resorption while maintaining normal bone formation.…”