As hydroxyapatite has good osteoconductive properties, it is used as coating material for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Silymarin promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration. System administration of silymarin increases bone strength and both cancellous and cortical bone mass. The aim of this study was to confirm the effect of the local incorporation silymarin into hydroxyapatite-coated titanium implants in the osteoporotic and normal condition. Twelve-week-old female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group sham, group ovariectomized and group silymarin, and the rats from ovariectomized and sham received hydroxyapatite implants and animals belong to group silymarin received silymarin-hydroxyapatite implants until death at 12 weeks, respectively. The bilateral femurs of rats were harvested for evaluation. All treatments increased new bone formation around the surface of titanium rods and push-out force other than group ovariectomized. Compared with group ovariectomized, group silymarin showed the strongest effects on new bone formation, biomechanical strength and regulation of osteogenesis and bone resorption-related gene expression, respectively. Additionally, these are significant difference in bone formation, gene expression and push-out force was observed among treatment groups. This finding suggests that local incorporation of silymarin is useful to improve the fixation of hydroxyapatite-coated implants in ovariectomized rats.
VirdiASIrishJSenaK, et al.
Sclerostin antibody treatment improves implant fixation in a model of severe osteoporosis. J Bone Joint Surg Am2015;
97: 133–140.
2.
StrömOBorgströmFKanisJA, et al.
Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos2011;
6: 59–155.
3.
Prevention NCDPoO.Osteoporosis prevention, diagnosis, and therapy. JAMA2001;
285: 785–795.
4.
KanisJABurletNCooperC, et al.
European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int2008;
19: 399–428.
5.
RossRDHamiltonJLWilsonBM, et al.
Pharmacologic augmentation of implant fixation in osteopenic bone. Curr Osteoporos Rep2013;
12: 55–64.
6.
HayashiKFotovatiAAliSA, et al.
Prostaglandin EP4 receptor agonist augments fixation of hydroxyapatite-coated implants in a rat model of osteoporosis. Bone Joint J2005;
87: 1150–1156.
7.
NakamuraYHayashiKAbu-AliS, et al.
Effect of preoperative combined treatment with alendronate and calcitriol on fixation of hydroxyapatite-coated implants in ovariectomized rats. J Bone Joint Surg Am2008;
90: 824–832.
8.
OzawaSOgawaTIidaK, et al.
Ovariectomy hinders the early stage of bone-implant integration: histomorphometric, biomechanical, and molecular analyses. Bone2002;
30: 137–143.
9.
TsiridisEGamieZConaghanPG, et al.
Biological options to enhance periprosthetic bone mass. Injury2007;
38: 704–713.
10.
LouSLvHLiZ, et al.
Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: a meta-analysis of randomised controlled trials. BMJ Open2018;
8: e015187.
11.
QinSZhangQZhangL.Effect of OPG gene mutation on protein expression and biological activity in osteoporosis. Exp Ther Med2017;
14: 1475–1480.
12.
TabatabaeimalazyOSalariPKhashayarP, et al.
New horizons in treatment of osteoporosis. Daru2017;
25: 2.
13.
CrocenziFARomaMG.Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication. CMC2006;
13.
14.
MurielP.NF-κB in liver diseases: a target for drug therapy. J Appl Toxicol2010;
29: 91–100.
15.
KavithaCVDeepGGangarSC, et al.
Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-κB, and AP-1 activation in RAW264.7 cells. Mol Carcinog2014;
53: 169–180.
16.
KimJHKimKJinHM, et al.
Silibinin inhibits osteoclast differentiation mediated by TNF family members. Mol Cells2009;
28: 201–207.
17.
YingXSunLChenX, et al.
Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling. Eur J Pharmacol2013;
721: 225–230.
18.
TaoZSZhouWSQiangZ, et al.
Intermittent administration of human parathyroid hormone (1-34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur. J Biomater Appl2016;
30: 952–960.
19.
TaoZSZhouWSBaiBL, 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. J Mater Sci Mater Med2016;
27: 43.
20.
YuXWeiM.Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method. J Biomed Mater Res B2011;
97B: 345–354.
21.
YuXJiangXRoweD, et al.
Biomimetic CaP coating incorporated with parathyroid hormone improves the osseointegration of titanium implant. J Mater Sci Mater Med2012;
23: 2177–2186.
22.
SongJEJeonYSTianJ, et al.
Evaluation of silymarin/duck's feet-derived collagen/hydroxyapatite sponges for bone tissue regeneration. Mater Sci Eng C2019;
97: 347–355.
23.
VarkeyMKucharskiCDoschakMR, et al.
Osteogenic response of bone marrow stromal cells from normal and ovariectomized rats treated with a low dose of basic fibroblast growth factor. Tissue Eng2007;
13: 809–817.
24.
ZhangYChengNMironR, et al.
Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials2012;
33: 6698–6708.
25.
TaoZSZhouWSTuKK, et al.
The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats. Injury2015;
46: 2164–2169.
26.
LiYFLiXDBaoCY, et al.
Promotion of peri-implant bone healing by systemically administered parathyroid hormone (1-34) and zoledronic acid adsorbed onto the implant surface. Osteoporos Int2013;
24: 1063–1071.
27.
GabetYKohaviDKohlerT, et al.
Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning. J Bone Miner Res2008;
23: 48–57.
28.
LiYLiQZhuS, et al.
The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials2010;
31: 9006–9014.
29.
TaoZSBaiBLHeXW, et al.
A comparative study of strontium-substituted hydroxyapatite coating on implant's osseointegration for osteopenic rats. Med Biol Eng Comput2016;
54: 1959–1968.
30.
TaoZSZhouWSHeXW, et al.
A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C2016;
62: 226–232.
31.
FabienWClairePLaurentL, et al.
The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem2013;
288: 6542–6551.
32.
BoneHGGreenspanSLMckeeverC, et al.
Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocr Metab2000;
85: 720–726.
33.
TaoZSLvYXCuiW, et al. Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats. [J]. Zeitschrift Für Gerontologie Und Geriatrie 2016; 49(5): 423–428.
34.
TaoZSQiangZTuKK, et al.
Treatment study of distal femur for parathyroid hormone (1-34) and beta-tricalcium phosphate on bone formation in critical size defects in rats. J Biomater Appl2015;
30: 484–491.
35.
TaoZSZhouWSTuKK, et al.
Treatment study of distal femur for parathyroid hormone (1-34) and beta-tricalcium phosphate on bone formation in critical-sized defects in osteopenic rats. J Craniomaxillofac Surg2015;
43: 2136–2143.
36.
HanHJKimSHanDH.Multifactorial evaluation of implant failure: a 19-year retrospective study. Int J Oral Maxillofac Implants2014;
29: 303–310.
37.
DavideCLucioMCarla RenataA.The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials2006;
27: 2331–2339.
38.
UezonoMTakakudaKKikuchiM, et al.
Hydroxyapatite/collagen nanocomposite-coated titanium rod for achieving rapid osseointegration onto bone surface. J Biomed Mater Res B2013;
101B: 1031–1038.
39.
SirinHTVargelIKutsalT, et al.
Ti implants with nanostructured and HA-coated surfaces for improved osseointegration. Artif Cells2015;
44: 1–8.
40.
El-ShitanyNASaharHKaremaED.Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine2010;
17: 116–125.
41.
DemirciBDostTGokalpF, et al.
Silymarin improves vascular function of aged ovariectomized rats. Phytother Res2014;
28: 868–872.
42.
Seidlová-WuttkeDBeckerTChristoffelV, et al.
Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. J Steroid Biochem Mol Biol2003;
86: 179–188.
43.
KimJLParkSHJeongD, et al.
Osteogenic activity of silymarin through enhancement of alkaline phosphatase and osteocalcin in osteoblasts and tibia-fractured mice. Exp Biol Med2012;
237: 417.
