Top

Knee Surgery, Sports Traumatology, Arthroscopy

Published in:

01-02-2013 | Experimental Study

Enhancement of bone formation with a synthetic matrix containing bone morphogenetic protein-2 by the addition of calcium citrate

Authors: Wei Wang, Qingyu Chen, Xiucui Li, Wei Zhang, Lei Peng, Liming Wang, Zhongqin Lin, Huazi Xu, Shifeng Song, Xiaolei Zhang, Shaowen Cheng, Dongquan Kou, Chuanzhu Lv, Ziming Yu

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 2/2013

Abstract

Purpose

The aim of the study was to test whether calcium citrate combined with rhBMP-2 was able to enhance bone regeneration compared with a matrix containing only rhBMP-2.

Methods

In each of experimental mice, one cylinder of calcium citrate–rhBMP-2 or rhBMP-2 alone was implanted into the thigh muscle pouches of the mouse. The following two treatment modalities were randomly allocated: (1) empty control with rhBMP-2 alone in a gelatin matrix and (2) a gelatin matrix including both calcium citrate and BMP-2. After several weeks, bone granules were obtained by histological analysis.

Results

Histomorphometric analysis showed the greatest amount of newly formed bone was observed in the group that contained 10.0 mg calcium citrate with 2.0 mg rhBMP-2 (p < 0.05). Quantitative histomorphometry revealed in the calcium citrate–rhBMP-2 group an obvious increase in the fractional area and the average new bone mineral density of newly formed bone at 2, 4 and 6 weeks than in the rhBMP-2 group (p < 0.05). At 2 weeks time-point, the mature cancellous bone had formed in the calcium citrate–rhBMP-2 group.

Conclusions

From this study, it can be concluded that calcium citrate combined with rhBMP-2 significantly enhances bone regeneration in muscle. This synthetic gelatin matrix containing calcium citrate/gelatin granules fulfils a number of criteria required for an ideal carrier system for rhBMP-2. The calcium ions that calcium citrate releases into the surrounding environment can activate bone formation when used as part of a combination of calcium citrate and BMP-2.

Adluri RS, Zhan L, Bagchi M, Maulik N, Maulik G (2010) Comparative effects of a novel plant-based calcium supplement with two common calcium salts on proliferation and mineralization in human osteoblast cells. Mol Cell Biochem 340(1–2):73–80PubMedCrossRef

Ehrenfried LM, Patel MH, Cameron RE (2008) The effect of tri-calcium phosphate (TCP) addition on the degradation of polylactide-co-glycolide (PLGA). J Mater Sci Mater Med 19(1):459–466PubMedCrossRef

Fowler BL, Dall BE, Rowe DE (1995) Complications associated with harvesting autogenous iliac bone graft. Am J Orthop (Belle Mead NJ) 24(12):895–903

Honda Y, Anada T, Kamakura S, Nakamura M, Sugawara S, Suzuki O (2006) Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line. Biochem Biophys Res Commun 345(3):1155–1160PubMedCrossRef

Jovanovic SA, Hunt DR, Bernard GW, Spiekermann H, Nishimura R, Wozney JM, Wikesjo UM (2003) Long-term functional loading of dental implants in rhBMP-2 induced bone. A histologic study in the canine ridge augmentation model. Clin Oral Implants Res 14(6):793–803PubMedCrossRef

Jung GY, Park YJ, Han JS (2010) Effects of HA released calcium ion on osteoblast differentiation. J Mater Sci Mater Med 21(5):1649–1654PubMedCrossRef

Jung RE, Weber FE, Thoma DS, Ehrbar M, Cochran DL, Hammerle CH (2008) Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate. Clin Oral Implants Res 19(2):188–195PubMedCrossRef

Kenny AM, Prestwood KM, Biskup B, Robbins B, Zayas E, Kleppinger A, Burleson JA, Raisz LG (2004) Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women. Osteoporos Int 15(4):290–294PubMedCrossRef

Kuo SY, Ho CM, Chen WC, Jan CR (2003) Sulfhydryl modification by 4,4′-dithiodipyridine induces calcium mobilization in human osteoblast-like cells. Arch Toxicol 77(11):630–637PubMedCrossRef

10.

Maeno S, Niki Y, Matsumoto H, Morioka H, Yatabe T, Funayama A, Toyama Y, Taguchi T, Tanaka J (2005) The effect of calcium ion concentration on osteoblast viability, proliferation and differentiation in monolayer and 3D culture. Biomaterials 26(23):4847–4855PubMedCrossRef

11.

Matsushita N, Terai H, Okada T, Nozaki K, Inoue H, Miyamoto S, Takaoka K (2006) Accelerated repair of a bone defect with a synthetic biodegradable bone-inducing implant. J Orthop Sci 11(5):505–511PubMedCrossRef

12.

Maus U, Andereya S, Gravius S, Ohnsorge JA, Niedhart C, Siebert CH (2008) BMP-2 incorporated in a tricalcium phosphate bone substitute enhances bone remodeling in sheep. J Biomater Appl 22(6):559–576PubMedCrossRef

13.

Misra DN (1996) Interaction of citric acid with hydroxyapatite: surface exchange of ions and precipitation of calcium citrate. J Dent Res 75(6):1418–1425PubMedCrossRef

14.

Mulconrey DS, Bridwell KH, Flynn J, Cronen GA, Rose PS (2008) Bone morphogenetic protein (RhBMP-2) as a substitute for iliac crest bone graft in multilevel adult spinal deformity surgery: minimum two-year evaluation of fusion. Spine (Phila Pa 1976) 33(20):2153–2159CrossRef

15.

Nakade O, Takahashi K, Takuma T, Aoki T, Kaku T (2001) Effect of extracellular calcium on the gene expression of bone morphogenetic protein-2 and -4 of normal human bone cells. J Bone Miner Metab 19(1):13–19PubMedCrossRef

16.

Nakamura S, Matsumoto T, Sasaki J, Egusa H, Lee KY, Nakano T, Sohmura T, Nakahira A (2010) Effect of calcium ion concentrations on osteogenic differentiation and hematopoietic stem cell niche-related protein expression in osteoblasts. Tissue Eng Part A 16(8):2467–2473PubMedCrossRef

17.

Nakamura Y, Wakitani S, Nakayama J, Wakabayashi S, Horiuchi H, Takaoka K (2003) Temporal and spatial expression profiles of BMP receptors and noggin during BMP-2-induced ectopic bone formation. J Bone Miner Res 18(10):1854–1862PubMedCrossRef

18.

Oda M, Kuroda S, Kondo H, Kasugai S (2009) Hydroxyapatite fiber material with BMP-2 gene induces ectopic bone formation. J Biomed Mater Res B Appl Biomater 90(1):101–109PubMed

19.

Qiu H, Yang J, Kodali P, Koh J, Ameer GA (2006) A citric acid-based hydroxyapatite composite for orthopedic implants. Biomaterials 27(34):5845–5854PubMedCrossRef

20.

Ripamonti U, Crooks J, Khoali L, Roden L (2009) The induction of bone formation by coral-derived calcium carbonate/hydroxyapatite constructs. Biomaterials 30(7):1428–1439PubMedCrossRef

21.

Sakhaee K, Poindexter JR, Griffith CS, Pak CY (2004) Stone forming risk of calcium citrate supplementation in healthy postmenopausal women. J Urol 172(3):958–961PubMedCrossRef

22.

Schaefer SL, Lu Y, Seeherman H, Li XJ, Lopez MJ, Markel MD (2009) Effect of rhBMP-2 on tibial plateau fractures in a canine model. J Orthop Res 27(4):466–471PubMedCrossRef

23.

Takagishi Y, Kawakami T, Hara Y, Shinkai M, Takezawa T, Nagamune T (2006) Bone-like tissue formation by three-dimensional culture of MG63 osteosarcoma cells in gelatin hydrogels using calcium-enriched medium. Tissue Eng 12(4):927–937PubMedCrossRef

24.

Thomas SD, Need AG, Tucker G, Slobodian P, O’Loughlin PD, Nordin BE (2008) Suppression of parathyroid hormone and bone resorption by calcium carbonate and calcium citrate in postmenopausal women. Calcif Tissue Int 83(2):81–84PubMedCrossRef

25.

Urist MR (1965) Bone: formation by autoinduction. Science 150(698):893–899PubMedCrossRef

26.

Urist MR, Lietze A, Dawson E (1984) Beta-tricalcium phosphate delivery system for bone morphogenetic protein. Clin Orthop Relat Res 187:277–280PubMed

27.

Valdes MA, Thakur NA, Namdari S, Ciombor DM, Palumbo M (2009) Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. Arch Orthop Trauma Surg 129(12):1651–1657PubMedCrossRef

28.

Yamazaki Y, Oida S, Akimoto Y, Shioda S (1988) Response of the mouse femoral muscle to an implant of a composite of bone morphogenetic protein and plaster of Paris. Clin Orthop Relat Res 234:240–249PubMed

29.

Yeo A, Rai B, Sju E, Cheong JJ, Teoh SH (2008) The degradation profile of novel, bioresorbable PCL-TCP scaffolds: an in vitro and in vivo study. J Biomed Mater Res A 84(1):208–218PubMed

Title: Enhancement of bone formation with a synthetic matrix containing bone morphogenetic protein-2 by the addition of calcium citrate
Authors: Wei Wang
Qingyu Chen
Xiucui Li
Wei Zhang
Lei Peng
Liming Wang
Zhongqin Lin
Huazi Xu
Shifeng Song
Xiaolei Zhang
Shaowen Cheng
Dongquan Kou
Chuanzhu Lv
Ziming Yu
Publication date: 01-02-2013
Publisher: Springer-Verlag
Published in: Knee Surgery, Sports Traumatology, Arthroscopy / Issue 2/2013
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI: https://doi.org/10.1007/s00167-012-1953-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Enhancement of bone formation with a synthetic matrix containing bone morphogenetic protein-2 by the addition of calcium citrate

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2013

Prospective clinical and radiological two-year results after patellofemoral arthroplasty using an implant with an asymmetric trochlea design

The influence of risk factors on clinical outcomes following anatomical medial patellofemoral ligament (MPFL) reconstruction using the gracilis tendon

MR imaging of anterior knee pain: a pictorial essay

Knee arthroplasty and bleeding: when to remove drainages

Acromioclavicular and coracoclavicular PDS augmentation for complete AC joint dislocation showed insufficient properties in a cadaver model

Effect of compression therapy on knee swelling and pain after total knee arthroplasty