Strontium ranelate (SrR) has both bone anabolic and anti-resorption properties and has therefore the potential to increase the healing of bone defects. The aim of the present study was to investigate the effect of systemic treatment with SrR during the healing of cortical bone defects in rats. In addition, the vertebral bodies were examined in order to elucidate the effect of short-term treatment with SrR on intact trabecular bone. Sixty 16-week-old female Wistar rats were randomized into four groups. A cylindrical defect was drilled through the anterior cortex of the mid-femoral diaphysis in both hind limbs. Two of the groups were treated with SrR (900 mg/kg b.w.) mixed into the food and two groups served as controls. The animals were euthanized after either 3 or 8 weeks of treatment. Healing of the defects was analyzed with µCT, mechanical testing, and stereology. Treatment with SrR resulted in increased thickness of the defects after 3 weeks of treatment, whereas no effect on bone volume fraction (BV/TV), mechanical properties (maximum strength and maximum stiffness), periosteal callus volume, or osteoclast-covered bone surfaces (Oc.S/BS) after either 3 or 8 weeks of treatment was found. Furthermore, SrR increased the bone material density (ρ) of the vertebral bodies, and tended to increase BV/TV after 8 weeks of treatment (p = 0.087). The mechanical properties of the vertebral bodies were not influenced by SrR treatment. In conclusion, 3 weeks of treatment with SrR increased the thickness of the healing mid-femoral cortical bone defects in rats, but did not influence BV/TV, mechanical properties, periosteal callus volume, or Oc.S/BS after either 3 or 8 weeks. Furthermore, SrR had no effect on the microstructure and mechanical properties of the vertebral bodies.
Rats Bone defects Bone healing Strontium ranelate MicroCT Biomechanics
This is a preview of subscription content, log in to check access.
The authors are grateful for the hard work and excellent technical assistance of Jytte Utoft. Thomas Dalager Jørgensen is acknowledged for his elegant graphical work. We thank Visiopharm for the contribution to the newCAST stereology software system and the Velux Foundation for the donation of the µCT scanner. The study was kindly supported by the Aarhus University Research Foundation and the Danish Council for Independent Research | Medical Sciences (0602-01706B).
JBV, AB, and JST designed the study. JBV, AB, TGS, and JST contributed to the experimental work. JBV prepared the first draft of the paper and is the guarantor. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.
Compliance with Ethical Standards
Conflict of interest
The authors Jens Bay Vegger, Annemarie Brüel, Thomas Givskov Sørensen, and Jesper Skovhus Thomsen declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
The experiment complied with the EU Directive 2010/63/EU for animal experiments, and all procedures were approved by the Danish Animal Inspectorate under the Danish Ministry of Justice.
Gerstenfeld LC, Sacks DJ, Pelis M et al (2009) Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res 24:196–208. doi:10.1359/jbmr.081113CrossRefPubMedGoogle Scholar
Aspenberg P, Genant HK, Johansson T et al (2010) Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 25:404–414. doi:10.1359/jbmr.090731CrossRefPubMedGoogle Scholar
Sikjaer T, Rejnmark L, Thomsen JS et al (2012) Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study. J Bone Miner Res 27:781–788. doi:10.1002/jbmr.1493CrossRefPubMedGoogle Scholar
Bouxsein ML, Boyd SK, Christiansen BA et al (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486. doi:10.1002/jbmr.141CrossRefPubMedGoogle Scholar
Ammann P, Shen V, Robin B et al (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020. doi:10.1359/JBMR.040906CrossRefPubMedGoogle Scholar
Boyd SK, Szabo E, Ammann P (2011) Increased bone strength is associated with improved bone microarchitecture in intact female rats treated with strontium ranelate: A finite element analysis study. Bone 48:1109–1116. doi:10.1016/j.bone.2011.01.004CrossRefPubMedGoogle Scholar