Effects of Preventive Long-Term Treatment with Strontium Ranelate and Zoledronic Acid on Bone Quality in Ovariectomized Rats
American Journal of Clinical and Experimental Medicine
Volume 4, Issue 6, November 2016, Pages: 191-200
Received: Sep. 3, 2016; Accepted: Sep. 18, 2016; Published: Nov. 15, 2016
Views 3197      Downloads 83
Marta Martín-Fernández, Biochemistry Investigation, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
Marina Gómez-Chinchón, Biochemistry Investigation, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
Luis Álvarez, Spinal Pathology Unit, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
Blanca Torrubia, Biochemistry Investigation, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
Manuel Díaz-Curiel, Internal Medicine, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
David Guede, Trabeculae, Limited Society, Technological Park of Galicia, Ourense, Spain
Jose Ramón Caeiro, Traumatology and Orthopedic Surgery, Universitary Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Cristobalina Rodríguez-Álvarez, Area of preventive Medicine and Public Health. Health Sciences Faculty, Medicine, University of La Laguna, Tenerife, Spain
Concepción de la Piedra, Biochemistry Investigation, Sanitary Research Institute Jimenez Diaz Foundation, Madrid, Spain
Article Tools
Follow on us
The aim of this work was to study the effects on bone quality produced by long-range treatment with zoledronic acid (ZA) or strontium ranelate (SrR) in ovariectomized rats. Sixty 6-month-old female Wistar rats were divided: SHAM (n=15), simulated intervention; OVX (n=15), ovariectomized; OVX+ZA (n=15), ovariectomized treated with ZA (0.083 mg/kg i. v. at the beginning of the study); and OVX+SrR (n=15), ovariectomized treated with SrR (0.033 g/kg/day by oral gavage). Rats were sacrificed 8 months later. Femoral (F) and lumbar (L) bone mineral density (BMD), trabecular and cortical microstructure, biomechanical testing and Raman spectrometry were performed. FBMD and LBMD decreased in OVX rats with no changes with SrR. ZA treatment prevented changes to BMD. Ovariectomy produced a reduction in micro-CT parameters, while SrR treatment did not avoid these changes. ZA treatment increased micro-CT parameters with respect to the SHAM group. The microstructural parameters of the cortical region were not modified in any of the groups. Ovariectomy produced a decrease in biomechanical parameters that was maintained with SrR. ZA treatment produced an increase in these parameters being higher than those of the SHAM group. Ovariectomy and treatments did not produce differences in crystallinity or substitution index. Mineralization index (MI) decreased in the OVX group. SrR did not revert this effect though ZA avoided it. According to our results preventive treatment with SrR did not revert the alterations in bone quality due to ovariectomy in rats. Treatment with ZA not only reverted the effects of ovariectomy, but also improved bone quality with respect to control rats.
Ovariectomized Rats, Zoledronic Acid, Strontium Ranelate
To cite this article
Marta Martín-Fernández, Marina Gómez-Chinchón, Luis Álvarez, Blanca Torrubia, Manuel Díaz-Curiel, David Guede, Jose Ramón Caeiro, Cristobalina Rodríguez-Álvarez, Concepción de la Piedra, Effects of Preventive Long-Term Treatment with Strontium Ranelate and Zoledronic Acid on Bone Quality in Ovariectomized Rats, American Journal of Clinical and Experimental Medicine. Vol. 4, No. 6, 2016, pp. 191-200. doi: 10.11648/j.ajcem.20160406.16
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Wariner AH, Curtis JR. Adherence to osteoporosis treatments: room for improvement. Curr Opin Rheumatol 2009 21: 356-62.
Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesembrink P, Hodson PK, Abrams K, Orloff JJ, Horowith Z, Eriksen FF, Boonen S . For the HORIZON recurrent fracture trial. N Eng J Med 2007; 357: 1799-1809.
Reginster JY, Bruyére O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, Devogelaer JP. Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone 2009; 45: 1059-64.
Kleerekoper M. Osteoporosis prevention and therapy: preserving and building strength through bone quality. Osteoporos Int 2006; 17: 1707–15.
Pistoia W, Van Rietbergen B, Rüegsegger P. Mechanical consequences of diferent scenarios for simulated bone athrophy and recovery in the distal radius. Bone 2003; 33: 937-45.
Borchers RE Gibson LJ, Burchardt H, Hayes WC. Effects of selected thermal variables on the mechanical properties of trabecular bone. Biomaterials 1995; 16: 545–51.
Gala Paniagua J, Díaz-Curiel M, De la Piedra Gordo C, CastillaReparaz C, TorralboGarcía M. Bone mass assessment in rats by dual energy X-ray absorptiometry. The British Journal of Radiology 1998; 71: 754–58.
Feldkamp LA, Davis LC. Practical cone-beam algorithm. Journal of the Optical Society of America 1984 ; 1:612–19
Hildebrand T, Ruegsegger P. A new method for the model-independent assessment of thickness in three-dimensional images. Journal of Microscopy 1997;185: 67–75.
Ulrich D, Van Rietbergen B, Laib A, R̈uegsegger P. The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone. Bone 1999; 25: 55–60.
Hildebrand T, Rüegsegger P. Quantification of Bone Microarchitecture with the Structure Model Index. Computer Methods in Biomechanics and Biomedical Engineering 1997; 1:15–23.
Odgaard A, Gundersen HJ. Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. Bone 1993; 14: 173-182.
Turner CH, Burr DB. Basic biomechanical measurements of bone: A tutorial. Bone 1993; 14: 595–608.
Iolascon G, Frizzi L, Di Pietro G, Capaldo A, Luciano F, Gimigliano F. Bone quality and bone strength: benefits of the bone-forming approach. Clin Cases Miner Bone Metab 2014; 11: 20-4.
Chen B, Li Y, Yang X, Xie D. Comparable effects of alendronate and strontium ranelate on femur in ovariectomized rats. Calcif. Tissue Int 2013; 93: 481–86.
Chen B, Li Y, Yang X, Xu H, Xie D. Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats. Osteoporos. Int. 2013 ; 24, 2115-21.
Boyd SK, Szabo E, Ammann P. Increased bone strength is associated with improved bone microarchitecture in intact female rats treated with strontium ranelate: A finite element analysis study. Bone 2011; 48, 1109–16.
Zacchetti G, RizZAi, Ammann P. Systemic treatment with strontium ranelate accelerates the filling of a critical size bone defect and improves the intrinsic quality of the healing bone. Bone 2012; 50, S57.
Ozturan KE, Demir B, Yucel I, Cakici H, Yilmaz F, Haberal A. Effect of strontium ranelate on fracture healing in the osteoporotic rats. J. Orthop. Res. 2011; 29, 138–42.
Yalin S, Sagir O, Comelekoglu U, Berkoz̈ M, Eroglu P. Strontium ranelate treatment improves oxidative damage in osteoporotic rat model. Pharmacol. Reports 2012; 64, 396–402.
Marie PJ, Host M, Modrowski D, De Poliak C, Guillemain J, Deloffre P. An uncoupling agent containing strontium prevents bone loss by depressing bone resorpion and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 1993 18: 547-51.
Ma YL, Zeng QQ, Porras LL, Harvey A, Moore TL, Shelbourn TL, Dalsky GP, Wronsky TJ, Aguirre JI, Bryant HU, Sato M. Teriparatide [rhPTH (1-34)], but not strontium ranelate, demonstrated bone anabolic efficacy in mature, osteopenic, ovariectomized rats. Endocrinology 2011; 152, 1767–78.
Brüel A, Vegger JB, Raffalt AC, Andersen JET, Thomsen JS. PTH (1-34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats. Bone 2013; 53, 51-8.
Khajuria DK, Razdan R, Mahapatra DR. Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats. Rev. Bras. Reumatol 2015; 55, 103–12.
Brennan MA, Gleeson JP, O’Brien F J, McNamara LM. Effects of ageing, prolonged estrogen deficiency and Zoledronate on bone tissue mineral distribution. J. Mech.Behav. Biomed. Mater 2014; 29: 161–70.
Palacio EP, Müller SS, Sardenberg T, MIzobuchi RR, Galbiatti JA, DUrigan A Jr, Savarese A, Ortolan EV. Detecting early biomechanical effects of zoledronic acid on femurs of osteoporotic female rats. J. Osteoporos 2012; 2012: 162806. doi 10.1155/2012/ 162806.
Wu, CC, Wang CC, Lu DH, Hsu LH, Yang KC, Lin FH. Calcium phosphate cement delivering Zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats. Biomed. Mater 2012; 7: 035009.
Querido W, Campos AP, Martins Ferreira EH, San Gil RA, Rossi AM, Farina M. Strontium ranelate changes the composition and crystal structure of the biological bone-like apatite produced in osteoblast cell cultures. Cell Tissue Res 2014; 357: 793–801.
Rossi AL, Moldovan S, Querido W, Rossi A, Werckman J, ERsen O, Farina M. Effect of strontium ranelate on bone mineral: Analysis of nanoscale compositional changes. Micron 2014; 56: 29–36.
Doublier A, Farlay D, Jaurand X, Vera R, Boivin GEffects of strontium on the quality of bone apatite crystals: A paired biopsy study in postmenopausal osteoporotic women. Osteoporos. Int. 2013; 24: 1079–87.
Gamsjaeger S, Hofstetter B, Zwettler E, Recker R, Gasser JA, Erikssen EF, Klaushofer K, Paschalis EP. Effects of 3 years treatment with once-yearly zoledronic acid on the kinetics of bone matrix maturation in osteoporotic patients. Osteoporos. Int 2013; 24: 339–47.
Dahl SG. Allain P, Marie PJ, Mauras Y, Boivin G, Ammamm P, Tsouderos Y, Delmas PD, Christiansen C. Incorporation and distribution of strontium in bone. Bone2001; 28: 446-53.
Reginster JY, Kaufman JM, Goemaere S, Devogelaer JP, Benhamou CL, FElsenberg D, Diza_curiel M, Brandi ML, Badurski J, Wark J, Balogh A, Bruyére O, Roux C. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos. Int 2012; 23: 1115–1122.
Bunyaratavej N. The action of Strontium ranelate: myth or reality. J. Med. Assoc. Thai 2011; 94 Suppl 5: S35–37.
Black DM, Reid IR, Cauley JA, Cpsman F, Leung PC, Lakatos P, Lippuner K, Cmmings SR, Hue TF, Mukhopadhyay A, Tan M, Aftring RP, Eastell R. The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J. Bone Miner. Res 2015; 30: 934–44.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186