Skip to main content
SpringerLink
Log in

Combined treatment with parathyroid hormone (1–34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model

  • Original Article
  • Published:
Medical & Biological Engineering & Computing Aims and scope Submit manuscript

Abstract

The objective of this study was to evaluate the effect of following combined treatment with parathyroid hormone (1–34) (PTH) and beta-tricalcium phosphate (β-TCP) on local bone formation in a rat 3-mm critical-size defect at distal femur. Twelve weeks after bilateral ovariectomy (OVX) and sham operation (sham), all animals were randomly divided into four groups: group OVX, group OVX + β-TCP, group sham, and group sham + β-TCP, then all rats underwent bone defect in the bilateral distal femurs, and β-TCP were implanted into critical-sized defects for group OVX + β-TCP and group sham + β-TCP. After defect operation, all animals were received following subcutaneous injections with PTH (60 μg/kg, three times a week) until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that systemic usage of PTH or local usage of β-TCP can increase the healing of defects in OVX or sham rats. Furthermore, treatments with PTH and β-TCP showed a stronger effect on accelerating the local bone formation than used alone. Osteoporosis can limit the function of PTH and/or β-TCP. The results from our study demonstrate that combination of PTH and β-TCP had an additive effect on local bone formation in non-osteoporosis and/or osteoporosis rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Andersson N, Lindberg MK, Ohlsson C, Andersson K, Ryberg B (2001) Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice. J Endocrinol 170(3):529–537

    Article  CAS  PubMed  Google Scholar 

  2. Barradas AMC, Fernandes HAM, Groen N, Chai YC, Schrooten J, van de Peppel J, van Leeuwen JPTM, van Blitterswijk CA, de Boer J (2012) A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells. Biomaterials 33(11):3205–3215. doi:10.1016/j.biomaterials.2012.01.020

    Article  CAS  PubMed  Google Scholar 

  3. Bashoor-Zadeh M, Baroud G, Bohner M (2011) Simulation of the in vivo resorption rate of beta-tricalcium phosphate bone graft substitutes implanted in a sheep model. Biomaterials 32(27):6362–6373. doi:10.1016/j.biomaterials.2011.05.030

    Article  CAS  PubMed  Google Scholar 

  4. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22(3):465–475. doi:10.1359/jbmr.061113

    Article  PubMed  Google Scholar 

  5. Cheng N, Dai J, Cheng X, Li S, Miron RJ, Wu T, Chen W, Zhang Y, Shi B (2013) Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model. J Mater Sci Mater Med 24(8):1963–1975. doi:10.1007/s10856-013-4945-y

    Article  CAS  PubMed  Google Scholar 

  6. Comelekoglu U, Bagis S, Yalin S, Ogenler O, Yildiz A, Sahin NO, Oguz I, Hatungil R (2007) Biomechanical evaluation in osteoporosis: ovariectomized rat model. Clin Rheumatol 26(3):380–384. doi:10.1007/s10067-006-0367-2

    Article  PubMed  Google Scholar 

  7. De Long WG, Einhorn TA, Koval K, Mckee M, Smith W, Sanders R, Watson T (2007) Bone, grafts and bone graft substitutes in orthopedic trauma surgery: a critical analysis. J Bone Joint Surg Am 89A(3):649–658. doi:10.2106/Jbjs.F.00465

    Google Scholar 

  8. Deal C, Gideon J (2003) Recombinant human PTH 1-34 (Forteo): an anabolic drug for osteoporosis. Cleve Clin J Med 70(7):585–586

    Article  PubMed  Google Scholar 

  9. Finkemeier CG (2002) Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 84-A(3):454–464

    PubMed  Google Scholar 

  10. Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–S27. doi:10.1016/j.injury.2005.07.029

    Article  PubMed  Google Scholar 

  11. Goulet JA, Senunas LE, DeSilva GL, Greenfield ML (1997) Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res 339:76–81

    Article  PubMed  Google Scholar 

  12. Hannan EL, Magaziner J, Wang JJ, Eastwood EA, Silberzweig SB, Gilbert M, Morrison RS, McLaughlin MA, Orosz GM, Siu AL (2001) Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes. JAMA 285(21):2736–2742

    Article  CAS  PubMed  Google Scholar 

  13. Hanseler P, Ehrbar M, Kruse A, Fischer E, Schibli R, Ghayor C, Weber FE (2015) Delivery of BMP-2 by two clinically available apatite materials: in vitro and in vivo comparison. J Biomed Mater Res Part A 103(2):628–638. doi:10.1002/jbm.a.35211

    Article  Google Scholar 

  14. Heiss C, Schieker M, Schnettler R (2008) Implantation of bone substitutes for tibial head fractures. Unfallchirurg 111(8):621–627. doi:10.1007/s00113-008-1463-3

    Article  CAS  PubMed  Google Scholar 

  15. Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40(6):1434–1446. doi:10.1016/j.bone.2007.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Investig 104(4):439–446. doi:10.1172/JCI6610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Khan SN, Tomin E, Lane JM (2000) Clinical applications of bone graft substitutes. Orthop Clin N Am 31(3):389–398

    Article  CAS  Google Scholar 

  18. Kuemmerle JF (2005) Endogenous IGF-I protects human intestinal smooth muscle cells from apoptosis by regulation of GSK-3 beta activity. Am J Physiol Gastrointest Liver Physiol 288(1):G101–G110. doi:10.1152/ajpgi.00032.2004

    Article  CAS  PubMed  Google Scholar 

  19. Le Guehennec L, Layrolle P, Daculsi G (2004) A review of bioceramics and fibrin sealant. Eur Cells Mater 8:1–10; discussion 10–11

  20. Li YF, Zhou CC, Li JH, Luo E, Zhu SS, Feng G, Hu J (2012) The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats. Osteoporos Int 23(4):1463–1474. doi:10.1007/s00198-011-1751-6

    Article  CAS  PubMed  Google Scholar 

  21. Marx J (2004) Coming to grips with bone loss. Science 305(5689):1420–1422. doi:10.1126/science.305.5689.1420

    Article  CAS  PubMed  Google Scholar 

  22. Miron RJ, Wei L, Bosshardt DD, Buser D, Sculean A, Zhang Y (2014) Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects. Clin Oral Invest 18(2):471–478

    Article  Google Scholar 

  23. Moazzaz P, Gupta MC, Gilotra MM, Gilotra MN, Maitra S, Theerajunyaporn T, Chen JL, Reddi AH, Martin RB (2005) Estrogen-dependent actions of bone morphogenetic protein-7 on spine fusion in rats. Spine 30(15):1706–1711

    Article  PubMed  Google Scholar 

  24. Mosekilde L, Torring O, Rejnmark L (2011) Emerging anabolic treatments in osteoporosis. Curr Drug Saf 6(2):62–74

    Article  CAS  PubMed  Google Scholar 

  25. Namkung-Matthai H, Appleyard R, Jansen J, Hao Lin J, Maastricht S, Swain M, Mason RS, Murrell GA, Diwan AD, Diamond T (2001) Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 28(1):80–86

    Article  CAS  PubMed  Google Scholar 

  26. O’Loughlin PF, Morr S, Bogunovic L, Kim AD, Park B, Lane JM (2008) Selection and development of preclinical models in fracture-healing research. J Bone Joint Surg 90(Supplement_1):79–84

    Article  PubMed  Google Scholar 

  27. Roux C, Wyman A, Hooven FH, Gehlbach SH, Adachi JD, Chapurlat RD, Compston JE, Cooper C, Diez-Perez A, Greenspan SL, Lacroix AZ, Netelenbos JC, Pfeilschifter J, Rossini M, Saag KG, Sambrook PN, Silverman S, Siris ES, Watts NB, Boonen S, investigators G (2012) Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women: the global longitudinal study of osteoporosis in women (GLOW). Osteoporos Int 23(12):2863–2871. doi:10.1007/s00198-012-1935-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sasso RC, LeHuec JC, Shaffrey C, Spine Interbody Research G (2005) Iliac crest bone graft donor site pain after anterior lumbar interbody fusion: a prospective patient satisfaction outcome assessment. J Spinal Disord Tech 18(Suppl):S77–S81

    Article  PubMed  Google Scholar 

  29. Sato M, Westmore M, Clendenon J, Smith S, Hannum B, Zeng GQ, Brommage R, Turner CH (2000) Three-dimensional modeling of the effects of parathyroid hormone on bone distribution in lumbar vertebrae of ovariectomized cynomolgus macaques. Osteoporos Int 11(10):871–880. doi:10.1007/s001980070047

    Article  CAS  PubMed  Google Scholar 

  30. Sen MK, Miclau T (2007) Autologous iliac crest bone graft: should it still be the gold standard for treating nonunions? Inj Int J Care Inj 38:S75–S80. doi:10.1016/j.injury.2007.02.012

    Article  Google Scholar 

  31. Skripitz R, Aspenberg P (2004) Parathyroid hormone–a drug for orthopedic surgery? Acta Orthop Scand 75(6):654–662

    Article  PubMed  Google Scholar 

  32. Skripitz R, Andreassen TT, Aspenberg P (2000) Parathyroid hormone (1-34) increases the density of rat cancellous bone in a bone chamber. A dose-response study. J Bone Joint Surg Br 82(1):138–141

    Article  CAS  PubMed  Google Scholar 

  33. Takahashi Y, Yamamoto M, Tabata Y (2005) Osteogenic differentiation of mesenchymal stem cells in biodegradable sponges composed of gelatin and beta-tricalcium phosphate. Biomaterials 26(17):3587–3596. doi:10.1016/j.biomaterials.2004.09.046

    Article  CAS  PubMed  Google Scholar 

  34. Tsai WC, Liao CJ, Wu CT, Liu CY, Lin SC, Young TH, Wu SS, Liu HC (2010) Clinical result of sintered bovine hydroxyapatite bone substitute: analysis of the interface reaction between tissue and bone substitute. J Orthop Sci 15(2):223–232. doi:10.1007/s00776-009-1441-9

    Article  CAS  PubMed  Google Scholar 

  35. Wei L, Ke J, Prasadam I, Miron RJ, Lin S, Xiao Y, Chang J, Wu C, Zhang Y (2014) A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects. Osteoporos Int 25(8):2089–2096. doi:10.1007/s00198-014-2735-0

    Article  CAS  PubMed  Google Scholar 

  36. Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29(11):2520–2526. doi:10.1002/jbmr.2269

    Article  PubMed  PubMed Central  Google Scholar 

  37. Yang N, Cui Y, Tan J, Fu X, Han X, Leng H, Song C (2014) Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats. J Bone Miner Metab 32(3):252–260. doi:10.1007/s00774-013-0496-z

    Article  CAS  PubMed  Google Scholar 

  38. Yingjie H, Ge Z, Yisheng W, Ling Q, Hung W, Kwoksui L, Fuxing P (2007) Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. Bone 41(4):631–638

    Article  PubMed  Google Scholar 

  39. Yu B, Zhao X, Yang C, Crane J, Xian L, Lu W, Wan M, Cao X (2012) Parathyroid hormone induces differentiation of mesenchymal stromal/stem cells by enhancing bone morphogenetic protein signaling. J Bone Miner Res 27(9):2001–2014. doi:10.1002/jbmr.1663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yuan HP, Fernandes H, Habibovic P, de Boer J, Barradas AMC, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD (2010) Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proc Natl Acad Sci USA 107(31):13614–13619. doi:10.1073/pnas.1003600107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yun JI, Wikesjo UM, Borke JL, Bisch FC, Lewis JE, Herold RW, Swiec GD, Wood JC, McPherson JC 3rd (2010) Effect of systemic parathyroid hormone (1-34) and a beta-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model. J Clin Periodontol 37(5):419–426. doi:10.1111/j.1600-051X.2010.01547.x

    Article  CAS  PubMed  Google Scholar 

  42. Zhang Y, Cheng N, Miron R, Shi B, Cheng X (2012) Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials 33(28):6698–6708

    Article  CAS  PubMed  Google Scholar 

Download references

Authors’ contributions

Zhou-Shan Tao implemented the tool, performed the experiments for the evaluation, analyzed the datasets, and wrote the manuscript; Kai-kai Tu and Zheng-Liang Huang helped with the implementation regarding experiments; Yu-Long Zhou, Qiang Zhou, and Tao Sun helped with the experiments data acquisition; Hong-Ming Xu, Yang-Xun Lv, and Wei Cui collaborated in the evaluation, analyzed the datasets, and wrote the manuscript; and Lei Yang collaborated in the design, coordinated all the workflow, and helped to draft, write, and review the manuscript. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China

    Zhou-Shan Tao, Kai-kai Tu, Zheng-Liang Huang, Qiang Zhou, Tao Sun, Hong-Ming Xu, Yu-Long Zhou & Lei Yang

  2. Department of Orthopaedic Surgery, Wenzhou Central Hospital, Wenzhou, 325000, Zhejiang, China

    Yang-Xun Lv

  3. Sichuan Provincial Orthopedics Hospital, NO. 132 West First Section First Ring Road, Chengdu, 610000, Sichuan, China

    Wei Cui

Authors
  1. Zhou-Shan Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai-kai Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zheng-Liang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qiang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Ming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu-Long Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang-Xun Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lei Yang.

Ethics declarations

Competing interests

The authors have declared that they have no competing interests.

Statement of ethical approval

Animals were handled with the approval of the Animal Experimentation Ethics Committee of Second Affiliated Hospital of Wenzhou Medical University.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tao, ZS., Tu, Kk., Huang, ZL. et al. Combined treatment with parathyroid hormone (1–34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model. Med Biol Eng Comput 54, 1353–1362 (2016). https://doi.org/10.1007/s11517-015-1402-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11517-015-1402-8

Keywords

Search

Navigation