Abstract

Strontium ranelate (SrR) is one of the pharmaceutical agents reported to be effective on the promotion of fracture healing. This study aimed to evaluate the integrative effect of the oral SrR with a topical Chinese herbal paste, namely, CDR, on facilitation of bone healing. The in vivo efficacy was evaluated using rats with tibial fracture. They were treated with either CDR topically, or SrR orally, or their combined treatments. The in vivo results illustrated a significant additive effect of CDR on SrR in increasing the yield load of the fractured tibia. The in vitro results showed that neither SrR nor CDR exhibited a cytotoxic effect on UMR106 and bone-marrow stem cell (BMSC), but both of them increased the proliferation of BMSC at low concentrations. The combination of CDR at 200 μg/mL with SrR at 200 or 400 μg/ml also showed an additive effect on increasing the ALP activity of BMSC. Both SrR and CDR alone reduced osteoclast formation, and the effective concentration of SrR to inhibit osteoclastogenesis was reduced in the presence of CDR. This integrative approach by combining oral SrR and topical CDR is effective in promoting fracture healing properly due to their additive effects on proosteogenic and antiosteoclastogenic properties.

Highlights

  • One of the commonest consultations in orthopaedic clinics relates to fracture

  • Biomechanical 4-point bending test illustrated that the yield load of the fractured tibia of the rats which received a high oral dose of Strontium ranelate (SrR) (600 mg/ml) together with topical CDR application at the same time (CDR + SrR600) was significantly higher than that of the control (Ctrl) by 66.3% (p < 0.05), CDR by 65.6% (p < 0.05), and SrR200 by 91.2% (p < 0.01) (Figure 1(a))

  • Similar observations were found in the analyses of the ultimate load (Figure 1(b)), failure load (Figure 1(c)), and stiffness (Figure 1(d)), except that no statistical significance was found when CDR + SrR600 was compared with Ctrl

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Summary

Introduction

One of the commonest consultations in orthopaedic clinics relates to fracture. The annual worldwide incidence of adult fractures is around 9.0–22.8 per 1000 people [1]. Patients with bone fracture require a long hospitalization time [2]. Orthopaedic surgeries are undoubtedly effective in fixing fractures. The healing process thereafter is seldom concerned by healthcare professionals in hospitals and clinics. The healing of the fracture relies on self-recovery. There are many scientific researchers working on the interventions to facilitate fracture healing, for instance, inventions of biophysical stimulations and applications of biomaterial scaffolds, as well as investigations on the efficacy of growth factors and bone morphogenetic proteins [7,8,9,10]. The clinical application of these interventions is yet controversial

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