Effects of Intermittent Teriparatide Administration on Bone Graft Healing and Local Simvastatin
Effects of Teriparatide on Bone Healing
,
Abstract
Introduction: Improving bone healing by various methods is one of the research areas of oral and maxillofacial surgery, as in the surgical branches dealing with hard tissue in medicine. Many methods, such as bone grafts, drugs, hormones, and tissue engineering applications, are used in bone reconstruction and rehabilitation. Moreover, improving bone healing is critical for better surgical outcomes. This study aimed to compare early and late period effects of intermittent teriparatide application on bone graft and local simvastatin application from histopathological, histomorphometric analysis, and biochemical aspects. Materials and Methods: 24 New Zealand rabbits were divided into four groups. While experimental groups received intermittent teriparatide (30µg/kg), control groups were given sterile distilled water. A total of 3 defects were created on each rabbit’s right and left tibia. Bone graft and local simvastatin were randomly applied to the opened defects, and one defect was left blank for control purposes. Rabbits were sacrificed on days 15 and 30 to examine early and late bone healing. Blood was drawn for biochemical analysis. Results: The healing score and new bone development in teriparatide applied and grafted defects were statistically significant compared to all groups (p<0.05). A statistically significant difference was obtained in grafted defects compared to the control group in teriparatide-applied defects. Local simvastatin caused necrosis in both experimental and control groups. Teriparatide administration does not cause a statistically significant change in calcium, potassium, and parathyroid hormone biomarkers (p>0.05).Conclusion: Better bone healing and bone graft healing in rabbits treated with teriparatide may encourage improved surgical outcomes in clinical practice. Keywords: Teriparatide; Intermittent; Bone healing; Bone graft; Simvastatin.
1. Matichescu A, Ardelean LC, Rusu LC et al. Advanced Biomaterials and Techniques for Oral Tissue Engineering and Regeneration-A Review. Materials (Basel) 2020;13(22): 5303. [Medline: 33238625] [doi: 10.3390/ma13225303]
2. Altundal, H, Sayrak, H, Yurtsever, E, Göker, K. Inhibitory effect of alendronate on bone resorption of autogenous free bone grafts in rats. J Oral Maxillofac Surg 2007;65(3): 508-516. [Medline: 17307600] [doi: 10.1016/j.joms.2005.11.054]
3. Koca CG, Kösehasanoğulları M. Evaluation of single-dose applied teriparatide effect on bone healing with histomorphometric and micro-ct analysis. J Craniomaxillofac Surg. 2021;49(2):98-103. [Medline: 33384204] [doi: 10.1016/j.jcms.2020.12.004]
4. Keskinrüzgar, A, Yanık, S, Aras, MH, Çetiner, S. Teriparatide [parathyroid hormone [1-34] and dentistry. Acta Odontol Turc 2015;32(3):165-170. [doi: http://dx.doi.org/10.17214/aot.74775]
5. Gupta S, Gabbro MD, Chang J. The impact of simvastatin intervention on the healing of bone, soft tissue, and TMJ cartilage in dentistry: a systematic review and meta-analysis. International Journal of Implant Dentistry 2019;5:17. [Medline: 30963362] [doi: 10.1186/s40729-019-0168-4]
6. Mundy G, Garrett R, Harris S et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999;286:1946–9. [Medline: 10583956] [doi: 10.1126/science.286.5446.1946]
7. Koca. C, Sadry S, Asker H, Çiçek M, Kösehasanoğullari M, Kaya G. Effects of the different administration frequencies of teriparatide (PTH [1‐34]) on new bone formation of expanded midpalatal sutures in rats: A histomorphometric and microcomputed tomography analysis. Orthodontics and Craniofacial Research 2021;24:449-457. [Medline: 34169642] [doi: 10.1111/ocr.12512]
8. Özer T, Başarlı Ö, Aktaş A, Barış E, Çelik, HH, Ocak, M. Locally administered single-dose teriparatide affects critical-size rabbit calvarial defects: a histological, histomorphometric, and micro-CT study. Acta Orthop Traumatol 2019;53:478-484. [Medline: 31530436] [doi: 10.1016/j.aott.2019.08.007]
9. Zandi, M, Dehghan A, Gheysari F, Rezaeian L, Mezerji, NMG. Evaluation of teriparatide effect on healing of autografted mandibular defects in rats. J Craniomaxillofac Surg 2019;47(1):120-126. [Medline: 30528562] [doi: 10.1016/j.jcms.2018.11.015]
10. Tang ZL, Zhang WJ, Wang DX, Chen JM, Ma H, Wu DR. An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone. J Oral Maxillofac Surg 2014;72(2):419-30. [Medline: 24071373] [doi: 10.1016/j.joms.2013.07.037]
11. Sugiura T, Kashii M, Matsuo Y et al. Intermittent administration of teriparatide enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis. Spine J 2015;15(2):298-306. [Medline: 25110274] [doi: 10.1016/j.spinee.2014.08.001]
12. 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 2013;24(10):2693-700. [Medline: 23756875] [doi: 10.1007/s00198-013-2385-7]
13. Hixon KR, Miller AN. Animal models of impaired long bone healing: Tissue engineering- and cell-based in vivo interventions. J Orthop Res 2022;40:767- 778. [Medline: 35072292] [doi: 10.1002/jor.25277]
14. Haffner-Luntzer M, Ignatius A. Animal models for studying metaphyseal bone fracture healing. European Cells and Materials 2020;40:172-188. [Medline: 33119886] [doi: 10.22203/eCM.v040a11]
15. Matos MA, Araujo FP, Paixao FB. Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation. Journal of Orthopaedic Surgery and Research 2008;3:4. [Medline: 18230175] [doi: 10.1186/1749-799X-3-4]
16. Yukata K, Xie C, Li TF et al. Teriparatide (human PTH(1–34)) compensates for impaired fracture healing in COX-2 deficient mice. Bone 2018;110:150–159. [Medline: 29408411] [doi: 10.1016/j.bone.2018.02.001]
17. Pelled G, Lieber R, Avalos P et al. Teriparatide (recombinant parathyroid hormone 1-34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy. J Tissue Eng Regen Med. 2020;14(8):1037–1049. [Medline: 32483878] [doi: 10.1002/term.3075]
18. Kuroshima S, Salihi ZA, Yamashita J. Parathyroid Hormone Related to Bone Regeneration in Grafted and Nongrafted Tooth Extraction Sockets in Rats. J Implant Dentistry 2013;22(1):71-76. [Medline: 23296032] [doi: 10.1097/ID.0b013e318278f94d]
19. Wu Z, Liu C, Zang G, Sun H. The effect of simvastatin on remodeling of the alveolar bone following tooth extraction. Int J Oral Maxillofac Surg 2008;37(2):170-6. [Medline: 17804200] [doi: 10.1016/j.ijom.2007.06.018]
20. Nyan M, Sato D, Oda M et al. Bone formation with the combination of simvastatin and calcium sulfate in critical sized rat calvarial defect. J Pharmacol Sci 2007;104(4):384-6. [Medline: 17721043] [doi: 10.1254/jphs.sc0070184]
21. Nyan M, Sato D, Kihara H, Machida T, Ohya K, Kasugai S. Effects of the combination with alpha- tricalcium phosphate and simvastatin on bone regeneration. Clin Oral Implants Res 2009;20(3):280-7. [Medline: 19397639] [doi: 10.1111/j.1600-0501.2008.01639.x]
22. Ma B, Clarke SA, Brooks RA, Rushton N. The effect of simvastatin on bone formation and ceramic resorption in a periimplant defect model. Acta Biomater 2008;4(1):149-55. [Medline: 17702682] [doi: 10.1016/j.actbio.2007.05.004]
23. Lima CEVC, Calixto JC, Anbinder AL. Influence of the association between simvastatin and demineralized bovine bone matrix on bone repair in rats. Braz. Oral Res 2011;25(1):42-48. [Medline: 21359450] [doi: 10.1590/s1806-83242011000100008]
24. Tao ZS, Zhou WS, Bai B et al. The effects of combined human parathyroid hormone (1–34) and simvastatin treatment on the interface of hydroxyapatite- coated titanium rods implanted into osteopenic rats femurs. Journal of Materials Science: Materials in Medicine 2016;27:43. [Medline: 26758890] [doi: 10.1007/s10856-015-5650-9.]
25. Leiyang LU, Bing LIU, Fei G, Jing Y. Effect of parathyroid combined with simvastatin on the differentiation of osteoblasts and the mRNA expression of OPG and RANKL. Chinese Journal of Osteoporosis 2014;20(7):750-754. [Doi: 10.3969.j.issn.1006-7108.2014.007.007]
2. Altundal, H, Sayrak, H, Yurtsever, E, Göker, K. Inhibitory effect of alendronate on bone resorption of autogenous free bone grafts in rats. J Oral Maxillofac Surg 2007;65(3): 508-516. [Medline: 17307600] [doi: 10.1016/j.joms.2005.11.054]
3. Koca CG, Kösehasanoğulları M. Evaluation of single-dose applied teriparatide effect on bone healing with histomorphometric and micro-ct analysis. J Craniomaxillofac Surg. 2021;49(2):98-103. [Medline: 33384204] [doi: 10.1016/j.jcms.2020.12.004]
4. Keskinrüzgar, A, Yanık, S, Aras, MH, Çetiner, S. Teriparatide [parathyroid hormone [1-34] and dentistry. Acta Odontol Turc 2015;32(3):165-170. [doi: http://dx.doi.org/10.17214/aot.74775]
5. Gupta S, Gabbro MD, Chang J. The impact of simvastatin intervention on the healing of bone, soft tissue, and TMJ cartilage in dentistry: a systematic review and meta-analysis. International Journal of Implant Dentistry 2019;5:17. [Medline: 30963362] [doi: 10.1186/s40729-019-0168-4]
6. Mundy G, Garrett R, Harris S et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999;286:1946–9. [Medline: 10583956] [doi: 10.1126/science.286.5446.1946]
7. Koca. C, Sadry S, Asker H, Çiçek M, Kösehasanoğullari M, Kaya G. Effects of the different administration frequencies of teriparatide (PTH [1‐34]) on new bone formation of expanded midpalatal sutures in rats: A histomorphometric and microcomputed tomography analysis. Orthodontics and Craniofacial Research 2021;24:449-457. [Medline: 34169642] [doi: 10.1111/ocr.12512]
8. Özer T, Başarlı Ö, Aktaş A, Barış E, Çelik, HH, Ocak, M. Locally administered single-dose teriparatide affects critical-size rabbit calvarial defects: a histological, histomorphometric, and micro-CT study. Acta Orthop Traumatol 2019;53:478-484. [Medline: 31530436] [doi: 10.1016/j.aott.2019.08.007]
9. Zandi, M, Dehghan A, Gheysari F, Rezaeian L, Mezerji, NMG. Evaluation of teriparatide effect on healing of autografted mandibular defects in rats. J Craniomaxillofac Surg 2019;47(1):120-126. [Medline: 30528562] [doi: 10.1016/j.jcms.2018.11.015]
10. Tang ZL, Zhang WJ, Wang DX, Chen JM, Ma H, Wu DR. An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone. J Oral Maxillofac Surg 2014;72(2):419-30. [Medline: 24071373] [doi: 10.1016/j.joms.2013.07.037]
11. Sugiura T, Kashii M, Matsuo Y et al. Intermittent administration of teriparatide enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis. Spine J 2015;15(2):298-306. [Medline: 25110274] [doi: 10.1016/j.spinee.2014.08.001]
12. 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 2013;24(10):2693-700. [Medline: 23756875] [doi: 10.1007/s00198-013-2385-7]
13. Hixon KR, Miller AN. Animal models of impaired long bone healing: Tissue engineering- and cell-based in vivo interventions. J Orthop Res 2022;40:767- 778. [Medline: 35072292] [doi: 10.1002/jor.25277]
14. Haffner-Luntzer M, Ignatius A. Animal models for studying metaphyseal bone fracture healing. European Cells and Materials 2020;40:172-188. [Medline: 33119886] [doi: 10.22203/eCM.v040a11]
15. Matos MA, Araujo FP, Paixao FB. Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation. Journal of Orthopaedic Surgery and Research 2008;3:4. [Medline: 18230175] [doi: 10.1186/1749-799X-3-4]
16. Yukata K, Xie C, Li TF et al. Teriparatide (human PTH(1–34)) compensates for impaired fracture healing in COX-2 deficient mice. Bone 2018;110:150–159. [Medline: 29408411] [doi: 10.1016/j.bone.2018.02.001]
17. Pelled G, Lieber R, Avalos P et al. Teriparatide (recombinant parathyroid hormone 1-34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy. J Tissue Eng Regen Med. 2020;14(8):1037–1049. [Medline: 32483878] [doi: 10.1002/term.3075]
18. Kuroshima S, Salihi ZA, Yamashita J. Parathyroid Hormone Related to Bone Regeneration in Grafted and Nongrafted Tooth Extraction Sockets in Rats. J Implant Dentistry 2013;22(1):71-76. [Medline: 23296032] [doi: 10.1097/ID.0b013e318278f94d]
19. Wu Z, Liu C, Zang G, Sun H. The effect of simvastatin on remodeling of the alveolar bone following tooth extraction. Int J Oral Maxillofac Surg 2008;37(2):170-6. [Medline: 17804200] [doi: 10.1016/j.ijom.2007.06.018]
20. Nyan M, Sato D, Oda M et al. Bone formation with the combination of simvastatin and calcium sulfate in critical sized rat calvarial defect. J Pharmacol Sci 2007;104(4):384-6. [Medline: 17721043] [doi: 10.1254/jphs.sc0070184]
21. Nyan M, Sato D, Kihara H, Machida T, Ohya K, Kasugai S. Effects of the combination with alpha- tricalcium phosphate and simvastatin on bone regeneration. Clin Oral Implants Res 2009;20(3):280-7. [Medline: 19397639] [doi: 10.1111/j.1600-0501.2008.01639.x]
22. Ma B, Clarke SA, Brooks RA, Rushton N. The effect of simvastatin on bone formation and ceramic resorption in a periimplant defect model. Acta Biomater 2008;4(1):149-55. [Medline: 17702682] [doi: 10.1016/j.actbio.2007.05.004]
23. Lima CEVC, Calixto JC, Anbinder AL. Influence of the association between simvastatin and demineralized bovine bone matrix on bone repair in rats. Braz. Oral Res 2011;25(1):42-48. [Medline: 21359450] [doi: 10.1590/s1806-83242011000100008]
24. Tao ZS, Zhou WS, Bai B et al. The effects of combined human parathyroid hormone (1–34) and simvastatin treatment on the interface of hydroxyapatite- coated titanium rods implanted into osteopenic rats femurs. Journal of Materials Science: Materials in Medicine 2016;27:43. [Medline: 26758890] [doi: 10.1007/s10856-015-5650-9.]
25. Leiyang LU, Bing LIU, Fei G, Jing Y. Effect of parathyroid combined with simvastatin on the differentiation of osteoblasts and the mRNA expression of OPG and RANKL. Chinese Journal of Osteoporosis 2014;20(7):750-754. [Doi: 10.3969.j.issn.1006-7108.2014.007.007]
| Files | ||
| Issue | Vol 11, No 1 (Winter 2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jcr.v11i1.16488 | |
| Keywords | ||
| Teriparatide Intermittent Bone healing Bone graft Simvastatin | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Acikgoz MM, Tilgen Yasasever C, Olgac NV, Cevher E, Ak G. Effects of Intermittent Teriparatide Administration on Bone Graft Healing and Local Simvastatin. J Craniomaxillofac Res. 2024;11(1):35-41.
