Skip to main content

Advertisement

Log in

Effect of intermittent PTH (1–34) on posterolateral spinal fusion with iliac crest bone graft in an ovariectomized rat model

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Intermittent treatment with high-dose parathyroid hormone (PTH) enhances the quantity and quality of the fusion callus and reduces healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague–Dawley rats. Intermittent PTH (1–34) could be an appropriate adjunctive therapy for osteoporotic patients undergoing posterolateral intertransverse process fusion.

Introduction

The study was designed to test the hypothesis that intermittent administration of PTH improves spinal fusion rates in a randomized controlled, ovariectomized osteoporotic rat spinal fusion model.

Methods

Thirty-six 10-week-old Sprague–Dawley rats were ovariectomized and underwent bilateral posterolateral L4–L5 spinal fusion with autologous iliac bone graft 6 weeks later. The experimental (PTH) group (18 rats) received daily subcutaneously administered injections of PTH (1–34) at 30 μg/kg/day starting on the day of operation. The control group (18 rats) received a subcutaneously administered injection of normal saline of the same volume. Nine rats from each group were sacrificed at 4 and 6 weeks. After sacrifice, the L4–L5 vertebral segments were removed and analyzed by plain radiographs, μ-CT, histomorphometry, and serum bone metabolism marker.

Results

The PTH group had a significantly higher fusion rate and X-ray fusion score than the control group at 4 and 6 weeks (p < 0.05). μ-CT and histological analysis showed that the fusion bone volume and cortical thickness for the PTH group were significantly higher than those for the control group at 4 and 6 weeks (p < 0.05). Metabolic marker analysis also showed significant difference between the two groups. The serum osteocalcin was significantly higher in the PTH group at 4 and 6 weeks, and levels of N-terminal peptide of type I collagen were significantly higher at 4 weeks (p < 0.05).

Conclusion

Intermittent treatment with high-dose PTH enhances the quantity of the fusion callus and reduces the healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague–Dawley rats.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. DeWald CJ, Stanley T (2006) Instrumentation-related complications of multilevel fusions for adult spinal deformity patients over age 65: surgical considerations and treatment options in patients with poor bone quality. Spine 31(19 Suppl):S144–S151

    Article  PubMed  Google Scholar 

  2. Andreassen TT, Willick GE, Morley P et al (2004) Treatment with parathyroid hormone hPTH(1–34), hPTH(1–31), and monocyclic hPTH(1–31) enhances fracture strength and callus amount after withdrawal fracture strength and callus mechanical quality continue to increase. Calcif Tissue Int 74(4):351–356

    Article  PubMed  CAS  Google Scholar 

  3. Rao RD, Bagaria V, Gourab K et al (2008) Autograft containment in posterolateral spine fusion. Spine J 8(4):563–569

    Article  PubMed  Google Scholar 

  4. Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L et al (2001) Effects of daily treatment with parathyroid hormone on bone micro-architecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16:1846–1853

    Article  PubMed  CAS  Google Scholar 

  5. Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R (1993) Anabolic actions of parathyroid hormone on bone. Endocrine Rev 14:690–709

    CAS  Google Scholar 

  6. Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V et al (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on estrogen with osteoporosis. Lancet 350:550–555

    Article  PubMed  CAS  Google Scholar 

  7. Erben RG, Weiser H, Sinowatz F, Rambeck WA, Zucker H (1992) Vitamin D metabolites prevent vertebral osteopenia in ovariectomized rats. Calcif Tissue Int 50(3):228–236

    Article  PubMed  CAS  Google Scholar 

  8. Cecchini MG, Fleisch H, Mühibauer RC (1997) Ipriflavone inhibits bone resorption in intact and ovariectomized rats. Calcif Tissue Int 61(Suppl 1):S9–S11

    Article  PubMed  CAS  Google Scholar 

  9. Mofidi A, Sedhom M, O’Shea K et al (2005) Is high level of disability an indication for spinal fusion? Analysis of long-term outcome after posterior lumbar interbody fusion using carbon fiber cages. J Spinal Disord Tech 18(6):479–484

    Article  PubMed  Google Scholar 

  10. Abe Y, Takahata M, Ito M et al (2007) Enhancement of graft bone healing by intermittent administration of human parathyroid hormone (1–34) in a rat spinal arthrodesis model. Bone 41(5):775–785

    Article  PubMed  CAS  Google Scholar 

  11. Grauer JN, Bomback DA, Lugo R et al (2004) Posterolateral lumbar fusions in athymic rats: characterization of a model. Spine J 4(3):281–286

    Article  PubMed  Google Scholar 

  12. Fleet JC, Bruns ME, Hock JM, Wood RJ (1994) Growth hormone and parathyroid hormone stimulate intestinal calcium absorption in aged female rats. Endocrinology 134(4):1755–1760

    Article  PubMed  CAS  Google Scholar 

  13. Nakazawa T, Nakajima A, Shiomi K et al (2005) Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1–34) on chondrogenesis in a model of experimental fracture healing. Bone 37(5):711–719

    Article  PubMed  CAS  Google Scholar 

  14. Misof BM, Roschger P, Cosman F et al (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88(3):1150–1156

    Article  PubMed  CAS  Google Scholar 

  15. Andreassen TT, Cacciafesta V (2004) Intermittent parathyroid hormone treatment enhances guided bone regeneration in rat calvarial bone defects. J Craniofac Surg 15(3):424–427

    Article  PubMed  Google Scholar 

  16. Komrakova M, Stuermer EK, Werner C et al (2010) Effect of human parathyroid hormone hPTH (1–34) applied at different regimes on fracture healing and muscle in ovariectomized and healthy rats. Bone 47(3):480–492

    Article  PubMed  CAS  Google Scholar 

  17. Hodsman AB, Bauer DC, Dempster DW et al (2005) Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 26(5):688–703

    Article  PubMed  CAS  Google Scholar 

  18. Nakajima A, Shimoji N, Shiomi K et al (2002) Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1–34). J Bone Miner Res 17(11):2038–2047

    Article  PubMed  CAS  Google Scholar 

  19. Giannoudis P, Tzioupis C, Almalki T et al (2007) Fracture healing in osteoporotic fractures: is it really different? A basic science perspective. Injury 38(Suppl 1):S90–S99

    Article  PubMed  Google Scholar 

  20. Wink CS (1982) Scanning electron microscopy of castrate rat bone. Calcif Tissue Int 34(6):547–552

    Article  PubMed  CAS  Google Scholar 

  21. Snider RK, Krumwiede NK, Snider LJ et al (1999) Factors affecting lumbar spinal fusion. J Spinal Disord 12(2):107–114

    Article  PubMed  CAS  Google Scholar 

  22. Lawrence JP, Ennis F, White AP et al (2006) Effect of daily parathyroid hormone (1–34) on lumbar fusion in a rat model. Spine J 6(4):385–390

    Article  PubMed  Google Scholar 

  23. O’Loughlin PF, Cunningham ME, Bukata SV et al (2009) Parathyroid hormone (1–34) augments spinal fusion, fusion mass volume, and fusion mass quality in a rabbit spinal fusion model. Spine 34(2):121–130

    Article  PubMed  Google Scholar 

  24. Komatsubara S, Mori S, Mashiba T et al (2005) Human parathyroid hormone (1–34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora. Bone 36(4):678–687

    Article  PubMed  CAS  Google Scholar 

  25. Turner RT, Evans GL, Lotinun S, Lapke PD, Iwaniec UT, Morey-Holton E (2007) Dose–response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats. J Bone Miner Res 22(1):64–71

    Article  PubMed  CAS  Google Scholar 

  26. Komatsu DE, Brune KA, Liu H et al (2009) Longitudinal in vivo analysis of the region-specific efficacy of parathyroid hormone in a rat cortical defect model. Endocrinology 150(4):1570–1579

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Wei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qiu, Z., Wei, L., Liu, J. et al. Effect of intermittent PTH (1–34) on posterolateral spinal fusion with iliac crest bone graft in an ovariectomized rat model. Osteoporos Int 24, 2693–2700 (2013). https://doi.org/10.1007/s00198-013-2385-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-013-2385-7

Keywords

Navigation