Abstract
Summary
This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR
Introduction
This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.
Methods
Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX + Veh), ALN (OVX + ALN), SR (OVX + SR), and ZOL (OVX + ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.
Results
ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P < 0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P < 0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P < 0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).
Conclusions
In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.
Similar content being viewed by others
References
Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287
Becker W, Hujoel PP, Becker BE et al (2000) Osteoporosis and implant failure: an exploratory case-control study. J Periodontol 71(4):625–31
Holahan CM, Koka S, Kennel KA et al (2008) Effect of osteoporotic status on the survival of titanium dental implants. Int J Oral Maxillofac Implants 23(5):905–910
Keller JC, Stewart M, Roehm M et al (2004) Osteoporosis-like bone conditions affect osseointegration of implants. Int J Oral Maxillofac Implants 19(5):687–694
Duarte PM, César Neto JB, Gonçalves PF et al (2003) Estrogen deficiency affects bone healing around titanium implants: a histometric study in rats. Implant Dent 12(4):340–346
Jensen TB, Bechtold JE, Chen X et al (2007) Systemic alendronate treatment improves fixation of press-fit implants: a canine study using nonloaded implants. J Orthop Res 25:772–778
Qi M, Hu J, Li J et al (2012) Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits. Bone 50(1):119–127
Duarte PM, de Vasconcelos Gurgel BC, Sallum AW et al (2005) Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogen-deficient rats. J Periodontol 76(1):107–114
Qi MC, Zhou XQ, Hu J et al (2004) Oestrogen replacement therapy promotes bone healing around dental implants in osteoporotic rats. Int J Oral Maxillofac Surg 33:279–285
Maïmoun L, Brennan TC, Badoud I et al (2010) Strontium ranelate improves implant osseointegration. Bone 46(5):1436–1441
Shirota T, Tashiro M, Ohno K et al (2003) Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats. J Oral Maxillofac Surg 61:471–480
Kimmel DB (2007) Mechanism of action, pharmacokinetic and pharmacodynamic profile, and clinical applications of nitrogen-containing bisphosphonates. J Dent Res 86(11):1022–1033
Bone HG, Hosking D, Devogelaer JP et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350(12):1189–1199
Rosen CJ, Hochberg MC, Bonnick SL et al (2005) Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res 20(1):141–151
Viera-Negrón YE, Ruan WH, Winger JN et al (2008) Effect of ovariectomy and alendronate on implant osseointegration in rat maxillary bone. J Oral Implantol 34:76–82
Chen BL, Xie DH, Zheng ZM et al (2011) Comparison of the effects of alendronate sodium and calcitonin on bone-prosthesis osseointegration in osteoporotic rats. Osteoporos Int 22(1):265–270
Gasser JA, Ingold P, Venturiere A et al (2008) Long-term protective effects of zoledronic acid on cancellous and cortical bone in the ovariectomized rat. J Bone Miner Res 23(4):544–551
Little DG, Smith NC, Williams PR et al (2003) Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis. J Bone Miner Res 18(7):1300–1307
Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822
Eastell R, Black DM, Boonen S et al (2009) Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density. J Clin Endocrinol Metab 94(9):3215–3225
Carvas JS, Pereira RM, Caparbo VF (2010) A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration. Osteoporos Int 21(10):1723–1729
Prieto-Alhambra D, Javaid MK, Judge A et al (2011) Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study. BMJ 343:d7222. doi:10.1136/bmj.d7222
Hilding M, Aspenberg P (2006) Postoperative clodronate decreases prosthetic migration: 4-year follow-up of a randomized radiostereometric study of 50 total knee patients. Acta Orthop 77:912–916
Friedl G, Radl R, Stihsen C et al (2009) The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial. J Bone Joint Surg Am 91:274–281
Reginster JY, Seeman E, De Vernejoul MC et al (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis, treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90(5):2816–22
Kanis JA, Johansson H, Oden A et al (2011) A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX(®). Osteoporos Int 22(8):2347–2355
Roux C, Fechtenbaum J, Kolta S et al (2008) Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis. Ann Rheum Dis 67(12):1736–1738
Liu JM, Wai-Chee Kung A, Pheng CS et al (2009) Efficacy and safety of 2 g day of strontium ranelate in Asian women with postmenopausal osteoporosis. Bone 45(3):460–465
Blake GM, Compston JE, Fogelman I (2009) Could strontium ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res 24(8):1354–1357
Marie PJ, Hott M, Modrowski D et al (1993) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615
Reginster JY (2002) Strontium ranelate in osteoporosis. Curr Pharm Des 8(21):1907–1916
Li Y, Feng G, Gao Y et al (2010) Strontium ranelate treatment enhances hydroxyapatite-coated titanium screws fixation inosteoporotic rats. J Orthop Res 28(5):578–582
Widler L, Jaeggi KA, Glatt M et al (2002) Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J Med Chem 45(17):3721–3738
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011) Guide for the Care and Use of Laboratory Animals: Eighth Edition. National Academies, Washington (DC), p 248
Chen BL, Li YQ, Xie DH et al (2012) Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats. J Orthop Res 30(5):733–739
Yildiz A, Esen E, Kürkçü M et al (2010) Effect of zoledronic acid on osseointegration of titanium implants: an experimental study in an ovariectomized rabbit model. J Oral Maxillofac Surg 68(3):515–23
Linderbäck P, Agholme F, Wermelin K et al (2012) Weak effect of strontium on early implant fixation in rat tibia. Bone 50(1):350–356
Yaffe A, Kollerman R, Bahar H et al (2003) The influence of alendronate on bone formation and resorption in a rat ectopic bone development model. J Periodontol 74(1):44–50
Nijenhuis T, van der Eerden BC, Hoenderop JG et al (2008) Bone resorption inhibitor alendronate normalizes the reduced bone thickness of TRPV5(-/-) mice. J Bone Miner Res 23(11):1815–1824
Bonnelye E, Chabadel A, Saltel F et al (2008) Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42(1):129–138
Su Y, Bonet J, Deloffre P et al (1992) The strontium salt S12911 inhibits bone resorption in mouse calvaria and isolated rat osteoclast cultures. J Bone Miner Res 17(Sl):188
Licata AA (1997) Bisphosphonate therapy. Am JMed Sci 313(1):17–22
Hadji P, Gamerdinger D, Spieler W et al (2012) Rapid Onset and Sustained Efficacy (ROSE) study: results of a randomised, multicentre trial comparing the effect of zoledronic acid or alendronate on bone metabolism in postmenopausal women with low bone mass. Osteoporos Int 23(2):625–633
Saag K, Lindsay R, Kriegman A et al (2007) A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone 40(5):1238–1243
Seedor JG, Quartuccio HA, Thompson DD (1991) The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats. J Bone Miner Res 6(4):339–46
Hansson U, Toksvig-Larsen S, Ryd L et al (2009) Once-weekly oral medication with alendronate does not prevent migration of knee prostheses: A double-blind randomized RSA study. Acta Orthop 80(1):41–45
Acknowledgments
This study was funded by the Guangdong Provincial Science and Technology Foundation in 2007 (NO2007B312004). The histological examination of this study was finished in The Center for New Drug Function Research, School of Life Science and Biopharmacology, Guangdong Pharmaceutical University. Thanks to Prof. QingNan Li for the help of histological examination. The biomechanical testing was finished in the Orthopedic Research Center of the First Affiliated Hospital of Sun Yat-sen University, and we thank JianWei Chen for the help of biomechanical testing.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Both BaiLing Chen and YiQiang Li are first co-authors.
Rights and permissions
About this article
Cite this article
Chen, B., Li, Y., Yang, X. et al. Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats. Osteoporos Int 24, 2115–2121 (2013). https://doi.org/10.1007/s00198-013-2288-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-013-2288-7