Skip to main content

Advertisement

Log in

Comparative Study on Osteoconductivity by Synthetic Octacalcium Phosphate and Sintered Hydroxyapatite in Rabbit Bone Marrow

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Octacalcium phosphate (OCP) is thought to be a precursor of the mineral crystals in biological apatite. Synthetic OCP has been shown to be converted into an apatite structure when implanted in murine calvarial bone, to enhance bone regeneration more than synthetic hydroxyapatite (HA), and to degrade faster than biodegradable β-tricalcium phosphate. This study was designed to investigate whether OCP implantation enhances the formation and resorption of new bone (remodeling) concomitant with OCP degradation when implanted intramedullary in a rabbit femur for 12 weeks, compared to sintered HA ceramic. Histological and histomorphometric analyses using undecalcified specimens showed that the area of bone apposition was significantly higher on OCP than on HA between 2 and 3 weeks, whereas it subsequently became smaller on OCP than on HA. The area attacked by multinucleated giant cells, including tartrate-resistant acid phosphatase (TRAP)-positive cells, was significantly higher for OCP than for HA at 8 weeks. Radiography revealed resorption of OCP but not of HA. The results disclose some osteoconductive characteristics of synthetic OCP in the bone marrow space: (1) enhancement of bone regeneration at the initial bone apposition stage and (2) stimulation of resorption of the newly formed bone coupled with OCP biodegradation mediated by TRAP-positive osteoclast-like cells. These results suggest that synthetic OCP would be a more useful bone substitute than HA in implant applications where rapid bone formation and concomitant implant resorption are important considerations.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Elliot JC (1965) The interpretation of the infrared absorption spectra of some carbonate-containing apatites. In: Fearnhead RW, Stack MV (eds), Tooth enamel. John Wright, Bristol, pp 20–22

    Google Scholar 

  2. Aoba T (1996) Recent observations on enamel crystal formation during mammalian amelogenesis. Anat Rec 245:208–218

    Article  CAS  PubMed  Google Scholar 

  3. Kim HM, Rey C, Glimcher MJ (1995) Isolation of calcium-phosphate crystals of bone by non-aqueous methods at low temperature. J Bone Miner Res 10:1589–1601

    Article  CAS  PubMed  Google Scholar 

  4. Brown WE, Smith JP, Lehr JR, Frazier AW (1962) Crystallographic and chemical relations between octacalcium phosphate and hydroxyapatite. Nature 196:1050–1055

    CAS  Google Scholar 

  5. Sauer GR, Wuthier RE (1988) Fourier transform infrared characterization of mineral phases formed during induction of mineralization by collagenase-released matrix vesicles in vitro. J Biol Chem 263:13718–13724

    CAS  PubMed  Google Scholar 

  6. Miake Y, Shimoda S, Fukae M, Aoba T (1993) Epitaxial overgrowth of apatite crystals on the thin-ribbon precursor at early stages of porcine enamel mineralization. Calcif Tissue Int 53:249–256

    Article  CAS  PubMed  Google Scholar 

  7. Bodier-Houlle P, Steuer P, Voegel JC, Cuisinier FJ (1998) First experimental evidence for human dentine crystal formation involving conversion of octacalcium phosphate to hydroxyapatite. Acta Crystallogr D Biol Crystallogr 54:1377–1381

    Article  CAS  PubMed  Google Scholar 

  8. Addadi L, Weiner S, Geva M (2001) On how proteins interact with crystals and their effect on crystal formation. Z Kardiol 90(suppl 3):92–98

    PubMed  Google Scholar 

  9. Boskey AL, (1998) Biomineralization: conflicts, challenges, and opportunities. J Cell Biochem Suppl 30/31:83–91

    Article  Google Scholar 

  10. Chickerur NS, Tung MS, Brown WE (1980) A mechanism for incorporation of carbonate into apatite. Calcif Tissue Int 32:55–62

    Article  CAS  PubMed  Google Scholar 

  11. Siew C, Gruninger SE, Chow LC, Brown WE (1992) Procedure for the study of acidic calcium phosphate precursor phases in enamel mineral formation. Calcif Tissue Int 50:144–148

    Article  CAS  PubMed  Google Scholar 

  12. Bucholz RW (2002) Nonallograft osteoconductive bone graft substitutes. Clin Orthop 395:44–52

    PubMed  Google Scholar 

  13. LeGeros RZ (2002) Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop 72:81–98

    Google Scholar 

  14. Ogose A, Hotta T, Kawashima H, Kondo N, Gu W, Kamura T, Endo N (2005) Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after excision of bone tumors. J Biomed Mater Res Appl Biomater 72:94–101

    Article  CAS  Google Scholar 

  15. Barrere F, van der Valk CM, Dalmeijer RA, Meijer G, van Blitterswijk CA, de Groot K, Layrolle P (2003) Osteogenicity of octacalcium phosphate coatings applied on porous metal implants. J Biomed Mater Res 66:779–788

    Article  CAS  Google Scholar 

  16. Barrere F, van der Valk CM, Dalmeijer RA, van Blitterswijk CA, de Groot K, Layrolle P (2003) In vitro and in vivo degradation of biomimetic octacalcium phosphate and carbonate apatite coatings on titanium implants. J Biomed Mater Res 64:378–387

    Article  CAS  Google Scholar 

  17. Bigi A, Bracci B, Cuisinier F, Elkaim R, Fini M, Mayer I, Mihailescu IN, Socol G, Sturba L, Torricelli P (2005) Human osteoblast response to pulsed laser deposited calcium phosphate coatings. Biomaterials 26:2381–2389

    Article  CAS  PubMed  Google Scholar 

  18. Dekker RJ, de Bruijn JD, Stigter M, Barrere F, Layrolle P, van Blitterswijk CA (2005) Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs. Biomaterials 26:5231–5239

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki O, Kamakura S, Katagiri T (2005) Surface chemistry and biological responses to synthetic octacalcium phosphate. J Biomed Mater Res Appl Biomater DOI: 10.1002/jbm.b.30407

    Google Scholar 

  20. Lu J, Descamps M, Dejou J, Koubi G, Hardouin P, Lemaitre J, Proust JP (2002) The biodegradation mechanism of calcium phosphate biomaterials in bone. J Biomed Mater Res 63:408–412

    Article  CAS  PubMed  Google Scholar 

  21. Lu JX, Gallur A, Flautre B, Anselme K, Descamps M, Thierry B, Hardouin P (1998) Comparative study of tissue reactions to calcium phosphate ceramics among cancellous, cortical, and medullar bone sites in rabbits. J Biomed Mater Res 42:357–367

    Article  CAS  PubMed  Google Scholar 

  22. Brown WE, Mathew M, Tung MS (1981) Crystal chemistry of octacalcium phosphate. Prog Crystal Growth Charact 4:59–87

    Article  CAS  Google Scholar 

  23. LeGeros RZ (1985) Preparation of octacalcium phosphate (OCP): a direct fast method. Calcif Tissue Int 37:194–197

    CAS  PubMed  Google Scholar 

  24. Suzuki O, Nakamura M, Miyasaka Y, Kagayama M, Sakurai M (1991) Bone formation on synthetic precursors of hydroxyapatite. Tohoku J Exp Med 164:37–50

    CAS  PubMed  Google Scholar 

  25. Suzuki O, Nakamura M, Miyasaka Y, Kagayama M, Sakurai M (1993) Maclura pomifera agglutinin-binding glycoconjugates on converted apatite from synthetic octacalcium phosphate implanted into subperiosteal region of mouse calvaria. Bone Miner 20:151–166

    Article  CAS  PubMed  Google Scholar 

  26. Mathew M, Brown W, Schroeder L, Dickens B (1988) Crystal-structure of octacalcium bis(hydrogenphosphate) tetrakis(phosphate) pentahydrate, Ca8(HPO4)2(PO4)4· 5H2O. J Cryst Spectrosc 18:235–250

    Article  CAS  Google Scholar 

  27. Sasano Y, Kamakura S, Homma H, Suzuki O, Mizoguchi I, Kagayama M (1999) Implanted octacalcium phosphate (OCP) stimulates osteogenesis by osteoblastic cells and/or committed osteoprogenitors in rat calvarial periosteum. Anat Rec 256:1–6

    Article  CAS  PubMed  Google Scholar 

  28. Fowler BO, Moreno EC, Brown WE (1966) Infra-red spectra of hydroxyapatite, octacalcium phosphate and pyrolysed octacalcium phosphate. Arch Oral Biol 11:477–492

    Article  CAS  PubMed  Google Scholar 

  29. Nelson DG, McLean JD (1984) High-resolution electron microscopy of octacalcium phosphate and its hydrolysis products. Calcif Tissue Int 36:219–232

    Article  CAS  PubMed  Google Scholar 

  30. Sarkar M, Wu AM, Kabat EA (1981) Immunochemical studies on the carbohydrate specificity of Maclura pomifera lectin. Arch Biochem Biophys 209:204–218

    Article  CAS  PubMed  Google Scholar 

  31. Nakamura M, Akita H, Mizoguchi I, Kagayama M (1989) A histochemical localization on Maclura pomifera lectin during osteogenesis. Histochemistry 92:225–230

    Article  CAS  PubMed  Google Scholar 

  32. Ishikawa Y, Valhmu WB, Wuthier RE (1987) Induction of alkaline phosphatase in primary cultures of epiphyseal growth plate chondrocytes by a serum-derived factor. J Cell Physiol 133:344–350

    Article  CAS  PubMed  Google Scholar 

  33. Ishikawa Y, Wu LN, Valhmu WB, Wuthier RE (1991) Fetuin and alpha-2HS glycoprotein induce alkaline phosphatase in epiphyseal growth plate chondrocytes. J Cell Physiol 149:222–234

    Article  CAS  PubMed  Google Scholar 

  34. Terkeltaub RA, Santoro DA, Mandel G, Mandel N (1988) Serum and plasma inhibit neutrophil stimulation by hydroxyapatite crystals. Evidence that serum alpha2-HS glycoprotein is a potent and specific crystal-bound inhibitor. Arthritis Rheum 31:1081–1089

    CAS  PubMed  Google Scholar 

  35. Anderson HC (1969) Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol 41:59–72

    Article  CAS  PubMed  Google Scholar 

  36. Hsu HH, Anderson HC (1978) Calcification of isolated matrix vesicles and reconstituted vesicles from fetal bovine cartilage. Proc Natl Acad Sci USA 75:3805–3808

    CAS  PubMed  Google Scholar 

  37. Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, Terkeltaub R, Millan JL (2002) Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci US A 99:9445–9449

    Article  CAS  Google Scholar 

  38. Suzuki O, Yagishita H, Yamazaki M, Aoba T (1995) Adsorption of bovine serum albumin onto octacalcium phosphate and its hydrolyzates. Cells Mater 5:45–54

    CAS  Google Scholar 

  39. Kamakura S, Nakajo S, Suzuki O, Sasano Y (2004) New scaffold for recombinant human bone morphogenetic protein-2. J Biomed Mater Res 71:299–307

    Article  CAS  Google Scholar 

  40. Kamakura S, Sasano Y, Homma-Ohki H, Nakamura M, Suzuki O, Kagayama M, Motegi K (1997) Multinucleated giant cells recruited by implantation of octacalcium phosphate (OCP) in rat bone marrow share ultrastructural characteristics with osteoclasts. J Electron Microsc (Tokyo) 46:397–403

    CAS  Google Scholar 

  41. Yamada S, Heymann D, Bouler JM, Daculsi G (1997) Osteoclastic resorption of biphasic calcium phosphate ceramic in vitro. J Biomed Mater Res 37:346–352

    Article  CAS  PubMed  Google Scholar 

  42. Doi Y, Iwanaga H, Shibutani T, Moriwaki Y, Iwayama Y (1999) Osteoclastic responses to various calcium phosphates in cell cultures. J Biomed Mater Res 47:424–433

    Article  CAS  PubMed  Google Scholar 

  43. Lu X, Leng Y (2005) Theoretical analysis of calcium phosphate precipitation in simulated body fluid. Biomaterials 26:1097–1108

    Article  CAS  PubMed  Google Scholar 

  44. Eidelman N, Chow LC, Brown WE (1987) Calcium phosphate saturation levels in ultrafiltered serum. Calcif Tissue Int 40:71–78

    CAS  PubMed  Google Scholar 

  45. Eidelman N, Brown WE, Meyer JL (1991) The effect of pyrophosphate concentrations on calcium-phosphate growth on well-crystallized octacalcium phosphate and hydroxyapatite seed crystals. J Crystal Growth 108:385–393

    Article  CAS  Google Scholar 

  46. Salimi MH, Heughebaert JC, Nancollas GH (1985) Crystal growth of calcium phosphates in the presence of magnesium ions. Langmuir 1:119–122

    Article  CAS  Google Scholar 

  47. Gupta A, Guo XL, Alvarez UM, Hruska KA (1997) Regulation of sodium-dependent phosphate transport in osteoclasts. J Clin Invest 100:538–549

    CAS  PubMed  Google Scholar 

  48. Prudhommeaux F, Schiltz C, Liote F, Hina A, Champy R, Bucki B, Ortiz-Bravo E, Meunier A, Rey C, Bardin T (1996) Variation in the inflammatory properties of basic calcium phosphate crystals according to crystal type. Arthritis Rheum 39:1319–1326

    CAS  PubMed  Google Scholar 

  49. Hang-Korng Ea BU, Rey C, Lioté F (2005) Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes. Arthritis Res Ther 7:R915–R926

    Article  PubMed  CAS  Google Scholar 

  50. Kamakura S, Sasano Y, Shimizu T, Hatori K, Suzuki O, Kagayama M, Motegi K (2002) Implanted octacalcium phosphate is more resorbable than beta-tricalcium phosphate and hydroxyapatite. J Biomed Mater Res 59:29–34

    Article  CAS  PubMed  Google Scholar 

  51. Brown WE, Eidelman N, Tomazic B (1987) Octacalcium phosphate as a precursor in biomineral formation. Adv Dent Res 1:306–313

    CAS  PubMed  Google Scholar 

  52. Doi Y, Shibutani T, Moriwaki Y, Kajimoto T, Iwayama Y (1998) Sintered carbonate apatites as bioresorbable bone substitutes. J Biomed Mater Res 39:603–610

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowlegements

The authors thank Drs. Yasuhisa Tanaka and Shoichi Nagaya, Tohoku University Graduate School of Medicine, for their many helpful suggestions and valuable criticism during preparation of the undecalcified tissue specimens and in the statistical analyses of histomorphometry. This study was supported in part by grants-in-aid (17076001, 16500285, 17659653, 17659603) from the Ministry of Education, Science, Sports, and Culture of Japan and grants from the Uehara Memorial Foundation, JFC Co., and JGC Corporation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. Suzuki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Imaizumi, H., Sakurai, M., Kashimoto, O. et al. Comparative Study on Osteoconductivity by Synthetic Octacalcium Phosphate and Sintered Hydroxyapatite in Rabbit Bone Marrow. Calcif Tissue Int 78, 45–54 (2006). https://doi.org/10.1007/s00223-005-0170-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0170-0

Keywords

Navigation