Abstract
Summary
The effect of human parathyroid hormone 1-34 (PTH) and zoledronic acid (ZA) alone or in combination on bone healing in osteoporotic settings was tested using implants inserted in tibiae of ovariectomized (OVX) rats. Combination therapy promoted bone healing more than each treatment alone 12 weeks after implant insertion.
Introduction
PTH and ZA have been demonstrated to be effective on implant fixation. However, reports about the combined use of PTH and ZA for promotion of bone healing around implant in osteoporotic settings are still limited. This study aims to investigate effects of PTH+ZA on implant stabilization in OVX rats.
Methods
Twelve weeks after bilateral ovariectomy, OVX rats randomly received implants without or with ZA (by immersion in 1 mg/ml ZA solution for 24 h). Subsequently, half of the animals from each group also received subcutaneous injections of PTH (60 μg/kg, three times a week) for 12 weeks. Thus, there were four groups: control, PTH, ZA, and PTH+ZA.
Results
All treatments promoted bone healing around implant compared to control, but PTH+ZA treatment showed significantly stronger effects than PTH or ZA alone in histological, micro-CT, and biomechanical tests.
Conclusion
The results indicated the additive effects of PTH and ZA on implant fixation in OVX rats; it was suggested that the anabolic effect of PTH was potent and not blunted by ZA during bone healing around implant when used concurrently.
Similar content being viewed by others
References
Brånemark PI, Hansson BO, Adell R, Breine U, Lindström J, Hallén O, Ohman A (1977) Osseointegrated implants in the treatment of edentuluous jaw. Experience from a 10-year period. Scand J Plast Reconstr Surg 16:1–132
Jacobs JJ, Sumner DR, Galante JO (1993) Mechanisms of bone loss associated with total hip replacement. Orthop Clin N Am 24:583–590
Neale SD, Haynes DR, Howie DW, Murray DW, Athanasou NA (2000) The effect of particle phagocytosis and metallic wear particles on osteoclast formation and bone resorption in vitro. J Arthroplasty 15:654–662
Neale SD, Sabokbar A, Howie DW, Murray DW, Athanasou NA (1999) Macrophage colony-stimulating factor and interleukin-6 release by periprosthetic cells stimulates osteoclast formation and bone resorption. J Orthop Res 17:686–694
No author listed (1993) Consensus development conference. Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 94:646-650
Fini M, Giavaresi G, Rimondini L, Giardino R (2002) Titanium alloy osseointegration in cancellous and cortical bone of ovariectomized animals: histomorphometric and bone hardness measurements. Int J Oral Maxillofac Implants 17:28–37
Rocca M, Fini M, Giavaresi G, Aldini NN, Giardino R (2002) Osteointegration of hydroxyapatite-coated and uncoated titanium screws in long-term ovariectomized sheep. Biomaterials 23:1017–10123
Tsiridis E, Gamie Z, Conaghan PG, Giannoudis PV (2007) Biological options to enhance periprosthetic bone mass. Injury 38:704–713
Gao Y, Zou SJ, Liu XG, Bao CY, Hu J (2009) The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats. Biomaterials 30:1790–1796
Hilding M, Aspenberg P (2007) Local preoperative treatment with a bisphosphonate improves the fixation of total knee prostheses: a randomized, double-blind radiostereometric study of 50 patients. Acta Orthop 78:795–799
Kneissel M, Boyde A, Gasser JA (2001) Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34). Bone 28:237–250
Gabet Y, Kohavi D, Müller R, Chorev M, Bab I (2005) Intermittently administered parathyroid hormone 1-34 reverses bone loss and structural impairment in orchiectomized adult rats. Osteoporos Int 16:1436–1443
Gabet Y, Müller R, Levy J, Dimarchi R, Chorev M, Bab I, Kohavi D (2006) Parathyroid hormone 1-34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis. Bone 39:276–282
Shirota T, Tashiro M, Ohno K, Yamaguchi A (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
Perilli E, Le V, Ma B, Salmon P, Reynolds K, Fazzalari NL (2010) Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats. Osteoporos Int 21:1371–1382
Lindsay R, Miller P, Pohl G, Glass EV, Chen P, Krege JH (2009) Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis. Osteoporos Int 20:943–948
Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res 21:366–373
Johansson HR, Skripitz R, Aspenberg P (2008) Bisphosphonates can block the deterioration in implant fixation after withdrawal of intermittent doses of parathyroid hormone. J Bone Joint Surg Br 90:400–404
Mair B, Tangl S, Feierfeil J, Skiba D, Watzek G, Gruber R (2009) Age-related efficacy of parathyroid hormone on osseointegration in the rat. Clin Oral Implants Res 20:400–405
Skripitz R, Johansson HR, Ulrich SD, Werner A, Aspenberg P (2009) Effect of alendronate and intermittent parathyroid hormone on implant fixation in ovariectomized rats. J Orthop Sci 14:138–143
Li Y, Li Q, Zhu S, Luo E, Li J, Feng G, Liao Y, Hu J (2010) The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials 31:9006–9014
Yoshinari M, Oda Y, Ueki H, Yokose S (2001) Immobilization of bisphosphonates on surface modified titanium. Biomaterials 22:709–715
Peter B, Pioletti DP, Laïb S, Bujoli B, Pilet P, Janvier P, Guicheux J, Zambelli PY, Bouler JM, Gauthier O (2005) Calcium phosphate drug delivery system: influence of local zoledronate release on bone implant osteointegration. Bone 36:52–60
Gabet Y, Kohavi D, Kohler T, Baras M, Müller R, Bab I (2008) Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning. J Bone Miner Res 23:48–57
Freeman TA, Patel P, Parvizi J, Antoci V Jr, Shapiro IM (2009) Micro-CT analysis with multiple thresholds allows detection of bone formation and resorption during ultrasound-treated fracture healing. J Orthop Res 27:673–679
Mashiba T, Tanizawa T, Takano Y, Takahashi HE, Mori S, Norimatsu H (1995) A histomorphometric study on effects of single and concurrent intermittent administration of human PTH (1-34) and bisphosphonate cimadronate on tibial metaphysis in ovariectomized rats. Bone 17:273S–278S
Zhang L, Endo N, Yamamoto N, Tanizawa T, Takahashi HE (1998) Effects of single and concurrent intermittent administration of human PTH (1-34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats. Tohoku J Exp Med 186:131–141
Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ, PaTH Study Investigators (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215
Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226
Cosman F, Eriksen EF, Recknor C, Miller PD, Guañabens N, Kasperk C, Papanastasiou P, Readie A, Rao H, Gasser JA, Bucci-Rechtweg C, Boonen S (2011) Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] in postmenopausal osteoporosis. J Bone Miner Res 26:503–511
Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446
Khosla S (2003) Parathyroid hormone plus alendronate. A combination that does not add up. N Engl J Med 349:1277–1279
Shirley D, Marsh D, Jordan G, McQuaid S, Li G (2005) Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res 23:1013–1021
Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117
Aspenberg P, Wermelin K, Tengwall P, Fahlgren A (2008) Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats. Acta Orthop 79:111–115
Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, Norimatsu H (2005) The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab 23(Suppl):36–42
Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M, American Society for Bone and Mineral Research (2010) Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 25:2267–2294
Tanizawa T, Yamamoto N, Takano Y, Mashiba T, Zhang L, Nishida S, Endo N, Takahashi HE, Fujimoto R, Hori M (1998) Effects of human PTH(1-34) and bisphosphonate on the osteopenic rat model. Toxicol Lett 102–103:399–403
Friedl G, Turner RT, Evans GL, Dobnig H (2007) Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism. J Orthop Res 25:1454–1464
Hashimoto T, Shigetomi M, Ohno T, Matsunaga T, Muramatsu K, Tanaka H, Sugiyama T, Taguchi T (2007) Sequential treatment with intermittent low-dose human parathyroid hormone (1-34) and bisphosphonate enhances large-size skeletal reconstruction by vascularized bone transplantation. Calcif Tissue Int 81:232–239
Johnston S, Andrews S, Shen V, Cosman F, Lindsay R, Dempster DW, Iida-Klein A (2007) The effects of combination of alendronate and human parathyroid hormone(1-34) on bone strength are synergistic in the lumbar vertebra and additive in the femur of C57BL/6J mice. Endocrinology 148:4466–4474
Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA (2005) Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am 87:731–741
Abtahi J, Tengvall P, Aspenberg P (2012) A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants. Bone 50:1148–1151
Acknowledgments
This study was supported by grant from the National Basic Research Program of China (973 Program, No. 2012CB933902).
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, Y.F., Li, X.D., Bao, C.Y. et al. Promotion of peri-implant bone healing by systemically administered parathyroid hormone (1-34) and zoledronic acid adsorbed onto the implant surface. Osteoporos Int 24, 1063–1071 (2013). https://doi.org/10.1007/s00198-012-2258-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-012-2258-5