The local application of recombinant human parathyroid hormone (1-34) promotes osseointegration of an immediate implant

doi:10.3969/j.issn.2095-4344.2017.26.019

Abstract

Abstract:

BACKGROUND: Based on a mouse model of tibial implantation, some scholars have found that the CaP-coated implant with recombinant human parathyroid hormone (1-34) (PTH(1-34)) shows strong osteogenesis effect at early stage, but this coating has not been applied in the oral environment

OBJECTIVE: To explore the role of local application of PTH(1-34) on immediate implant osseointegration .

METHODS: Nine New Zealand white rabbits were randomly divided into two groups (six in experimental group and three in control group). All of the tooth sockets were filled with heterogeneous freeze-dried bone firstly after four incisors of each rabbit were extracted. In the experimental group, a titanium screw with PTH(1-34) loaded CaP coating was implanted into each tooth socket, while in the control group, a titanium screw with only CaP coating was implanted. The animals were executed respectively at 4, 8, 12 weeks after operation, and the intact maxillary and mandibular specimens were harvested and tested by gross observation, bone density analysis, torque test, histologic al observation, X-ray observation.

RESULTS AND CONCLUSION: The gray value and maximum torque value of regenerated osseous tissue at different time points in the experimental group were significantly higher than those in the control group (P < 0.05). Within 4-12 weeks after implantation, regenerated and mature bone tissue appeared earlier in the experimental group than the control group. A large amount of new blood vessels were seen in the experimental group at 8 weeks after implantation, while in the control group, there were only few new blood vessels. To conclude, the local application of PTH(1-34) can promote bone formation, improve the implant-bone bonding strength, and enhance the stability of the implant.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Dental Implants, Teriparatide, Osseointegration, Tissue Engineering

CLC Number:

R318

Sun Zhi-hui, Zheng Yu, Wang Li-jie, Fan Shi-feng, Hou Xiao-wei.

The local application of recombinant human parathyroid hormone (1-34) promotes osseointegration of an immediate implant

[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(26): 4210-4216.

Figures/Tables 4

References

[1]Brennan-Calanan RM,Genco RJ,Wilding GE,et al. Osteoporosis and oral infection: Independent risk factors for oral bone loss.J Dent Res.2008;87(4):323-327．

[2]Prank K,Nowlan SJ,Harms HM,et al.Time series prediction of plasma hormone concentration. Evidence for differences in predictability of parathyroid hormone secretion between osteoporoctic patients and normal controls.J Clin Invest.1995; 95(6):2910-2919.

[3]Blind E,Raue F,Knappe V,et al.Cyclic AMP formation in rat bone and kidney cells is stimulated equally by parathyroid hormone-related protein (PTHrP) 1-34 and PTH 1-34. Exp Clin Endocrinol.1993;101(3):150-155.

[4]四川美康医药软件研究开发有限公司.药物临床信息参考[M].成都:四川科学技术出版社,2007:1507-1508.

[5]Yu XH,Wang LP,Jiang X,et al.Biomimetic CaP coating incorporated with parathyroid hormone improves the osseointegration of titanium implant.J Mater Sci Mater Med. 2012;23(9):2177-2186.

[6]Brnemark PI,Hansson BO,Adell R,et al. Osseointegrated implants in the treatment of the edentulous jaw．Experience from a 10-year period.Scand J Plast Reconstr Surg Suppl. 1977;16:1-132．

[7]Marquezan M,Osorio A,Sant’ Anna E,et al. Does bone mineral density influence the primary stability of dental implants? A systematic review.Clin Oral Implants Res.2012;23(7):767~774．

[8]中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊治指南(2011年)[J].中华骨质疏松和骨矿盐疾病杂志, 2011, 4(1):2-17.

[9]Binte AR,Tanaka M,Kohno S,et al.Relationship between porotic changes in alveolar bone and spinal osteoporosis.J Dent Res.2007;86(1):52-57.

[10]Khosla S,Westendorf JJ,Oursler MJ. Building bone to reverse osteoporosis and repair fractures.J Clin Invest. 2008;118(2): 421-428.

[11]梁红.内源性及外源性甲状旁腺激素对小鼠拔牙创骨愈合的影响[D].南京医科大学,2010.

[12]Tang ZL,Zhang WJ,Wang DX,et al.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):419-430．

[13]Deshpande SS,Gallagher KK,Donneys A,et al.Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis. Plast Reconstr Surg.2013;132(1):91-100.

[14]Reynolds DG,Takahata M,Lerner AL,et al.Teriparatide therapy enhances devitalized femoral allograft osseointegration and biomechanics in a murine model. Bone.2011;48(3):562-570.

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

[16]Jilka RL,Weinstein RS,Bellido T,et al.Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.J Clin Invest.1999;104(4):439-446.

[17]Chen HL,Demiralp B,Schneider A,et al.Parathyroid hormone and parathyroid hormone-related protein exert both pro- and anti-apoptotic effects in mesenchymal cells.J Biol Chem.2002; 277(22):19374-19381.

[18]Dobnig H,Turner RT.Evidence that intermittent treatment with parathyroid hormone increase bone formation in adult rats by activation of bone lining cells. Endocrinology.1995;136(8): 3632-3638.

[19]Gasser JA,Kneissel M,Thomsen JS,et al. PTH and interactions with bisphoshonates.J Musculoskelet Neuronal Interact.2000;1(1):53-56．

[20]Hodsman AB,Steer BM.Early histomorphometric changes in response to parathyroid hormone therapy in osteoporosis: Evidence for de novo bone formation on quiescent cancellous surfaces.Bone.1993;14(3):523-527.

[21]Jilka RL,O'Brien CA,Ali AA,et al.Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts.Bone.2009;44(2):275-286．

[22]Rickard DJ,Wang FL,Rodriguez-Rojas AM,et al.Intermittent treatment with parathyroid hormone(PTH)as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells. Bone.2006;39(6):1361-1372.

[23]唐雯菁,杜艳萍,洪维,等.甲状旁腺素对骨髓间充质干细胞增殖、分化和旁分泌功能的影响[J].中华骨质疏松和骨矿盐疾病杂志, 2014,7(1):42-47.

[24]Frisch SM.cAMP takes controls.Nat Cell Biol. 2000;2(9): E167-168．

[25]Drake MT,Srinivasan B,Mdder UI,et al.Effects of intermittent parathyroid hormone treatment on osteoprogenitor cells in postmenopausal women.Bone.2011;49(3):349-355．

[26]Neer M,Slovik DM,Daly M,et al.Treatment of postmenopausal osteoporosis with daily parathyroid hormone plus calcitriol. Osteoporos Int.1993;3(1):204-205.

[27]Burr DB,Hirano T,Turner CH,et al.Intermittently administered human parathyroid hormone (1-34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgous monkeys.J Bone Miner Res.2001;16(1):157-165.

[28]Sato M.Westmore M,Ma YL,et al.Teriparatide [PTH(1-34)] strengthens the proximal femur of onariectomized nonhuman primates despite increasing porosity.J Bone Miner Res. 2004; 19(4):623-629.

[29]Datta NS,Abou-Samra AB.PTH and PTHrP signaling in osteoblasts.Cell Signal.2009; 21(8):1245-1254.

[30]卫红艳,朱梅.甲状旁腺素治疗骨质疏松研究进展[J].药品评价, 2013,10(5):40-44.

[31]王晶晶,孟维艳,张喆,等.负载 PTH(1-34) 聚乳酸微球体外促成骨分化作用的研究[J].实用口腔医学杂志,2015,31(3):360-364.

[32]于美娜.负载PTH(1-34)的温水凝胶的制备及细胞学研究[D].吉林大学,2013.

[33]Valderrama P,Jung RE,Thoma DS,et al.Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: A histomorphometric study in dogs.J Periodontol. 2010;81(5): 737-747．

[34]Yu X,Wei M.Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method.J Biomed Mater Res B Appl Biomater.2011;97(2):345-354.

[35]李德超,刘惠萍,李慕勤,等.具有微弧氧化-硅烷-褪黑素复合膜层钛合金种植体的体内骨结合[J].中国组织工程研究, 2016, 20(43):6438-6444.

[36]Weng J,Wang M,Chen J.Plasma-sprayed calcium phosphate particles with high bioactivity and their use in bioactive scaffolds.Biomaterials.2002;23(13):2623-2629.

[37]Milella E,Cosentino F,Licciulli A,et al.Preparation and characterisation of titania/hydroxyapatite composite coatings obtained by sol-gel process. Biomaterials. 2001;22(11): 1425-1431.

[38]邓炜,王贻宁.仿生溶液生长法磷酸钙涂层种植体的研究进展[J].国外医学口腔医学分册,2001,28(2):76-78.

[39]Junker R,Dimakis A,Thoneick M,et al.Effects of implant surface coatings and composition on bone integration: a systematic review.Clin Oral Implants Res. 2009;20(4): 185-206.

[40]Luong LN,McFalls KM,Kohn DH.Gene delivery via DNA incorporation within a biomimetic apatite coating. Biomaterials. 2009;30(36):6996-7004.

[41]Stigter M,Bezemer J,de Groot K,et al.Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.J Control Release.2004;99(1):127-137.

[42]Liu Y,Li JP,Hunziker EB,et al.Incorporation of growth factors into medical devices via biomimetic coatings.Philos Trans A Math Phys Eng Sci.2006;364(1838):233-248.

[43]Wang CX,Liu JJ,Xiao Y,et al.Study on preparation and activity of a novel recombinant human parathyroid hormone(1-34) analog with N-terminal Pro-Pro extension. Regul Pept.2007; 141(1-3):35-43.