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Erschienen in: Journal of Bone and Mineral Metabolism 6/2018

26.12.2017 | Original Article

Effects of combined human parathyroid hormone (1–34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats

verfasst von: Hang Li, Qiang Zhou, Bing-Li Bai, She-Ji Weng, Zong-Yi Wu, Zhong-Jie Xie, Zhen-Hua Feng, Liang Cheng, Viraj Boodhun, Lei Yang

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 6/2018

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Abstract

The objective of this study was to investigate the effects of human parathyroid hormone (1–34) (PTH1–34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague–Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1–34 (60 μg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1–34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.
Literatur
1.
Zurück zum Zitat Patel A, Pavlou G, Mújica-Mota RE, Toms AD (2015) The epidemiology of revision total knee and hip arthroplasty in England and Wales: a comparative analysis with projections for the United States. A study using the National Joint Registry dataset. Bone Joint J 97-B:1076–1081CrossRef Patel A, Pavlou G, Mújica-Mota RE, Toms AD (2015) The epidemiology of revision total knee and hip arthroplasty in England and Wales: a comparative analysis with projections for the United States. A study using the National Joint Registry dataset. Bone Joint J 97-B:1076–1081CrossRef
2.
Zurück zum Zitat Tao ZS, Zhou WS, Bai BL, Cui W, Lv YX, Yu XB, Huang ZL, Tu KK, Zhou Q, Sun T (2016) 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 Med 27:43CrossRef Tao ZS, Zhou WS, Bai BL, Cui W, Lv YX, Yu XB, Huang ZL, Tu KK, Zhou Q, Sun T (2016) 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 Med 27:43CrossRef
3.
Zurück zum Zitat Duarte PM, César Neto JB, Gonçalves PF, Sallum EA, Jf N (2003) Estrogen deficiency affects bone healing around titanium implants: a histometric study in rats. Implant Dent 12:340CrossRef Duarte PM, César Neto JB, Gonçalves PF, Sallum EA, Jf N (2003) Estrogen deficiency affects bone healing around titanium implants: a histometric study in rats. Implant Dent 12:340CrossRef
4.
5.
Zurück zum Zitat Jinno T, Kirk SS, Goldberg VM (2004) Effects of calcium ion implantation on osseointegration of surface-blasted titanium alloy femoral implants in a canine total hip arthroplasty model. J Arthroplast 19:102–109CrossRef Jinno T, Kirk SS, Goldberg VM (2004) Effects of calcium ion implantation on osseointegration of surface-blasted titanium alloy femoral implants in a canine total hip arthroplasty model. J Arthroplast 19:102–109CrossRef
6.
Zurück zum Zitat Sul YT, Johansson C, Byon E, Albrektsson T (2005) The bone response of oxidized bioactive and non-bioactive titanium implants. Biomaterials 26:6720–6730CrossRef Sul YT, Johansson C, Byon E, Albrektsson T (2005) The bone response of oxidized bioactive and non-bioactive titanium implants. Biomaterials 26:6720–6730CrossRef
7.
Zurück zum Zitat Tao ZS, Zhou WS, Tu KK, Huang ZL, Zhou Q, Sun T, Lv YX, Cui W, Yang L (2015) 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. Injury 46:2164–2169CrossRef Tao ZS, Zhou WS, Tu KK, Huang ZL, Zhou Q, Sun T, Lv YX, Cui W, Yang L (2015) 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. Injury 46:2164–2169CrossRef
8.
Zurück zum Zitat Reikeras O, Gunderson RB (2003) Excellent results of HA coating on a grit-blasted stem: 245 patients followed for 8–12 years. Acta Orthop Scand 74:140CrossRef Reikeras O, Gunderson RB (2003) Excellent results of HA coating on a grit-blasted stem: 245 patients followed for 8–12 years. Acta Orthop Scand 74:140CrossRef
9.
Zurück zum Zitat Palm L, Jacobsson SA, Ivarsson I (2002) Hydroxyapatite coating improves 8- to 10-year performance of the link RS cementless femoral stem. J Arthroplast 17:172–175CrossRef Palm L, Jacobsson SA, Ivarsson I (2002) Hydroxyapatite coating improves 8- to 10-year performance of the link RS cementless femoral stem. J Arthroplast 17:172–175CrossRef
10.
Zurück zum Zitat Hara T, Hayashi K, Nakashima Y, Kanemaru T, Iwamoto Y (1999) The effect of hydroxyapatite coating on the bonding of bone to titanium implants in the femora of ovariectomised rats. J Bone Joint Surg Br 81:705–709CrossRef Hara T, Hayashi K, Nakashima Y, Kanemaru T, Iwamoto Y (1999) The effect of hydroxyapatite coating on the bonding of bone to titanium implants in the femora of ovariectomised rats. J Bone Joint Surg Br 81:705–709CrossRef
11.
Zurück zum Zitat Hayashi K, Uenoyama K, Mashima T, Sugioka Y (1994) Remodelling of bone around hydroxyapatite and titanium in experimental osteoporosis. Biomaterials 15:11–16CrossRef Hayashi K, Uenoyama K, Mashima T, Sugioka Y (1994) Remodelling of bone around hydroxyapatite and titanium in experimental osteoporosis. Biomaterials 15:11–16CrossRef
12.
Zurück zum Zitat Mavrogenis AF, Dimitriou R, Parvizi J, Babis GC (2009) Biology of implant osseointegration. J Musculoskel Neuron 9:61 Mavrogenis AF, Dimitriou R, Parvizi J, Babis GC (2009) Biology of implant osseointegration. J Musculoskel Neuron 9:61
13.
Zurück zum Zitat Fini M, Giavaresi G, Rimondini L, Giardino R (2002) Titanium alloy osseointegration in cancellous and cortical bone of ovariectomized animals: histomorphometric and bone hardness measurements. Int J Oral Maxillofac Implants 17:28–37PubMed Fini M, Giavaresi G, Rimondini L, Giardino R (2002) Titanium alloy osseointegration in cancellous and cortical bone of ovariectomized animals: histomorphometric and bone hardness measurements. Int J Oral Maxillofac Implants 17:28–37PubMed
14.
Zurück zum Zitat Gabet Y, Müller R, Levy J, Dimarchi R, Chorev M, Bab I, Kohavi D (2006) Parathyroid hormone 1–34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis. Bone 39:276–282CrossRef Gabet Y, Müller R, Levy J, Dimarchi R, Chorev M, Bab I, Kohavi D (2006) Parathyroid hormone 1–34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis. Bone 39:276–282CrossRef
15.
Zurück zum Zitat Tao ZS, Qiang Z, Tu KK, Huang ZL, Xu HM, Sun T, Lv YX, Cui W, Yang L (2015) Treatment study of distal femur for parathyroid hormone (1–34) and β-tricalcium phosphate on bone formation in critical-sized defects in rats. J Craniomaxillofac Surg 43:2136–2143CrossRef Tao ZS, Qiang Z, Tu KK, Huang ZL, Xu HM, Sun T, Lv YX, Cui W, Yang L (2015) Treatment study of distal femur for parathyroid hormone (1–34) and β-tricalcium phosphate on bone formation in critical-sized defects in rats. J Craniomaxillofac Surg 43:2136–2143CrossRef
16.
Zurück zum Zitat Shirota T, Tashiro M, Ohno K, Yamaguchi A (2003) Effect of intermittent parathyroid hormone (1–34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats. J Oral Maxillofac Surg 61:471–480CrossRef Shirota T, Tashiro M, Ohno K, Yamaguchi A (2003) Effect of intermittent parathyroid hormone (1–34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats. J Oral Maxillofac Surg 61:471–480CrossRef
18.
Zurück zum Zitat Shiraki M, Shiraki Y, Aoki C, Miura M (2000) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res 15:515–521CrossRef Shiraki M, Shiraki Y, Aoki C, Miura M (2000) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res 15:515–521CrossRef
19.
Zurück zum Zitat Iwamoto I, Kosha S, Noguchi SI, Murakami M, Fujino T, Douchi T, Nagata Y (1999) A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women; a comparative study with vitamin D3 and estrogen–progestin therapy. Maturitas 31:161–164CrossRef Iwamoto I, Kosha S, Noguchi SI, Murakami M, Fujino T, Douchi T, Nagata Y (1999) A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women; a comparative study with vitamin D3 and estrogen–progestin therapy. Maturitas 31:161–164CrossRef
20.
Zurück zum Zitat Shimizu T, Takahata M, Kameda Y, Hamano H, Ito T, Kimura-Suda H, Todoh M, Tadano S, Iwasaki N (2014) Vitamin K-dependent carboxylation of osteocalcin affects the efficacy of teriparatide (PTH 1–34) for skeletal repair. Bone 64:95–101CrossRef Shimizu T, Takahata M, Kameda Y, Hamano H, Ito T, Kimura-Suda H, Todoh M, Tadano S, Iwasaki N (2014) Vitamin K-dependent carboxylation of osteocalcin affects the efficacy of teriparatide (PTH 1–34) for skeletal repair. Bone 64:95–101CrossRef
21.
Zurück zum Zitat Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, Ishida N, Nakagawa M, Takechi M, Sano Y (2001) Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 17:315–321CrossRef Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, Ishida N, Nakagawa M, Takechi M, Sano Y (2001) Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 17:315–321CrossRef
22.
Zurück zum Zitat Yamaguchi M, Kakuda H, Ying HG, Tsukamoto Y (2000) Prolonged intake of fermented soybean (natto) diets containing vitamin K2 (menaquinone-7) prevents bone loss in ovariectomized rats. J Bone Miner Metab 18:71–76CrossRef Yamaguchi M, Kakuda H, Ying HG, Tsukamoto Y (2000) Prolonged intake of fermented soybean (natto) diets containing vitamin K2 (menaquinone-7) prevents bone loss in ovariectomized rats. J Bone Miner Metab 18:71–76CrossRef
23.
Zurück zum Zitat Mawatari T, Hiromasa MMD, Higaki H, Moro-Oka T, Kurata K, Murakami T, Iwamoto Y (2000) Effect of vitamin K2 on three-dimensional trabecular microarchitecture in ovariectomized rats. J Bone Miner Res 15:1810–1817CrossRef Mawatari T, Hiromasa MMD, Higaki H, Moro-Oka T, Kurata K, Murakami T, Iwamoto Y (2000) Effect of vitamin K2 on three-dimensional trabecular microarchitecture in ovariectomized rats. J Bone Miner Res 15:1810–1817CrossRef
24.
Zurück zum Zitat Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamazaki K (2009) Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 27:66–75CrossRef Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamazaki K (2009) Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 27:66–75CrossRef
25.
Zurück zum Zitat Iwamoto J (2014) Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients 6:1971–1980CrossRef Iwamoto J (2014) Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients 6:1971–1980CrossRef
26.
Zurück zum Zitat Nagura N, Komatsu J, Iwase H, Hosoda H, Ohbayashi O, Nagaoka I, Kaneko K (2015) Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats. Biomed Rep 3:295–300CrossRef Nagura N, Komatsu J, Iwase H, Hosoda H, Ohbayashi O, Nagaoka I, Kaneko K (2015) Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats. Biomed Rep 3:295–300CrossRef
27.
Zurück zum Zitat Chen B, Li Y, Xie D, Yang X (2012) Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats. J Orthop Res 30:733–739CrossRef Chen B, Li Y, Xie D, Yang X (2012) Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats. J Orthop Res 30:733–739CrossRef
28.
Zurück zum Zitat Virdi AS, Liu M, Sena K, Maletich J, Mcnulty M, Ke HZ, Sumner DR (2012) Sclerostin antibody increases bone volume and enhances implant fixation in a rat model. J Bone Joint Surg Am 94:1670–1680CrossRef Virdi AS, Liu M, Sena K, Maletich J, Mcnulty M, Ke HZ, Sumner DR (2012) Sclerostin antibody increases bone volume and enhances implant fixation in a rat model. J Bone Joint Surg Am 94:1670–1680CrossRef
29.
Zurück zum Zitat Li YF, Zhou CC, Li JH, Luo E, Zhu SS, Feng G, Hu J (2012) The effects of combined human parathyroid hormone (1–34) and zoledronic acid treatment on fracture healing in osteoporotic rats. Osteoporos Int 23:1463–1474CrossRef Li YF, Zhou CC, Li JH, Luo E, Zhu SS, Feng G, Hu J (2012) The effects of combined human parathyroid hormone (1–34) and zoledronic acid treatment on fracture healing in osteoporotic rats. Osteoporos Int 23:1463–1474CrossRef
30.
Zurück zum Zitat He F, Yang G, Wang X, Zhao S (2009) Effect of electrochemically deposited nanohydroxyapatite on bone bonding of sandblasted/dual acid-etched titanium implant. Int J Oral Maxillofac Implants 24:790PubMed He F, Yang G, Wang X, Zhao S (2009) Effect of electrochemically deposited nanohydroxyapatite on bone bonding of sandblasted/dual acid-etched titanium implant. Int J Oral Maxillofac Implants 24:790PubMed
31.
Zurück zum Zitat Li YF, Li XD, Bao CY, Chen QM, Zhang H, Hu J (2013) Promotion of peri-implant bone healing by systemically administered parathyroid hormone (1–34) and zoledronic acid adsorbed onto the implant surface. Osteoporos Int 24:1063–1071CrossRef Li YF, Li XD, Bao CY, Chen QM, Zhang H, Hu J (2013) Promotion of peri-implant bone healing by systemically administered parathyroid hormone (1–34) and zoledronic acid adsorbed onto the implant surface. Osteoporos Int 24:1063–1071CrossRef
32.
Zurück zum Zitat Gabet Y, Kohavi D, Kohler T, Baras M, Müller R, Bab I (2008) Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning. J Bone Miner Res 23:48–57CrossRef Gabet Y, Kohavi D, Kohler T, Baras M, Müller R, Bab I (2008) Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning. J Bone Miner Res 23:48–57CrossRef
33.
Zurück zum Zitat Li Y, Li Q, Zhu S, Luo E, Li J, Feng G, Liao Y, Hu J (2010) The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials 31:9006–9014CrossRef Li Y, Li Q, Zhu S, Luo E, Li J, Feng G, Liao Y, Hu J (2010) The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials 31:9006–9014CrossRef
34.
Zurück zum Zitat Tao ZS, Zhou WS, He XW, Liu W, Bai BL, Zhou Q, Huang ZL, Tu KK, Li H, Sun T (2016) A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C Mater Biol Appl 62:226CrossRef Tao ZS, Zhou WS, He XW, Liu W, Bai BL, Zhou Q, Huang ZL, Tu KK, Li H, Sun T (2016) A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C Mater Biol Appl 62:226CrossRef
35.
Zurück zum Zitat Turner RT, Vandersteenhoven JJ, Bell NH (2010) The effects of ovariectomy and 17 beta-estradiol on cortical bone histomorphometry in growing rats. J Bone Miner Res 2:115–122CrossRef Turner RT, Vandersteenhoven JJ, Bell NH (2010) The effects of ovariectomy and 17 beta-estradiol on cortical bone histomorphometry in growing rats. J Bone Miner Res 2:115–122CrossRef
36.
Zurück zum Zitat Koshihara Y, Hoshi K (1997) Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res 12:431–438CrossRef Koshihara Y, Hoshi K (1997) Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res 12:431–438CrossRef
37.
Zurück zum Zitat Vermeer C, Jie KS, Knapen MH (1995) Role of vitamin K in bone metabolism. Annu Rev Nutr 15:1–22CrossRef Vermeer C, Jie KS, Knapen MH (1995) Role of vitamin K in bone metabolism. Annu Rev Nutr 15:1–22CrossRef
38.
Zurück zum Zitat Hara K, Akiyama Y, Nakamura T, Murota S, Morita I (1995) The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone 16:179–184CrossRef Hara K, Akiyama Y, Nakamura T, Murota S, Morita I (1995) The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone 16:179–184CrossRef
39.
Zurück zum Zitat Iwasaki Y, Yamato H, Murayama H, Takahashi T, Ezawa I, Kurokawa K, Fukagawa M (2002) Menatetrenone prevents osteoblast dysfunction in unilateral sciatic neurectomized rats. Jpn J Pharmacol 90:88–93CrossRef Iwasaki Y, Yamato H, Murayama H, Takahashi T, Ezawa I, Kurokawa K, Fukagawa M (2002) Menatetrenone prevents osteoblast dysfunction in unilateral sciatic neurectomized rats. Jpn J Pharmacol 90:88–93CrossRef
40.
Zurück zum Zitat Matsumoto T, Miyakawa T, Yamamoto D (2012) Effects of vitamin K on the morphometric and material properties of bone in the tibiae of growing rats. Metabolism 61:407–414CrossRef Matsumoto T, Miyakawa T, Yamamoto D (2012) Effects of vitamin K on the morphometric and material properties of bone in the tibiae of growing rats. Metabolism 61:407–414CrossRef
41.
Zurück zum Zitat Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214CrossRef Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214CrossRef
42.
Zurück zum Zitat Saito M, Fujii K, Soshi S, Tanaka T (2005) Effects of vitamin B6 and vitamin K2 on bone mechanical properties and collagen crosslinks in spontaneously diabetic WBN/Kob rats. J Bone Miner Res Suppl SU420 Saito M, Fujii K, Soshi S, Tanaka T (2005) Effects of vitamin B6 and vitamin K2 on bone mechanical properties and collagen crosslinks in spontaneously diabetic WBN/Kob rats. J Bone Miner Res Suppl SU420
43.
Zurück zum Zitat Roy ME, Nishimoto SK, Rho JY, Bhattacharya SK, Lin JS, Pharr GM (2001) Correlations between osteocalcin content, degree of mineralization, and mechanical properties of C. carpio rib bone. J Biomed Mater Res 54:547–553CrossRef Roy ME, Nishimoto SK, Rho JY, Bhattacharya SK, Lin JS, Pharr GM (2001) Correlations between osteocalcin content, degree of mineralization, and mechanical properties of C. carpio rib bone. J Biomed Mater Res 54:547–553CrossRef
44.
Zurück zum Zitat Dayer R, Brennan TC, Rizzoli R, Ammann P (2010) PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet. Osteoporos Int 21:957–967CrossRef Dayer R, Brennan TC, Rizzoli R, Ammann P (2010) PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet. Osteoporos Int 21:957–967CrossRef
45.
Zurück zum Zitat Dayer R, Badoud I, Rizzoli R, Ammann P (2007) Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. J Bone Miner Res 22:1526–1533CrossRef Dayer R, Badoud I, Rizzoli R, Ammann P (2007) Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. J Bone Miner Res 22:1526–1533CrossRef
46.
Zurück zum Zitat Ichikawa T, Horieinoue K, Ikeda K, Blumberg B, Inoue S (2007) Vitamin K2 induces phosphorylation of protein kinase a and expression of novel target genes in osteoblastic cells. J Mol Endocrinol 39:4–239CrossRef Ichikawa T, Horieinoue K, Ikeda K, Blumberg B, Inoue S (2007) Vitamin K2 induces phosphorylation of protein kinase a and expression of novel target genes in osteoblastic cells. J Mol Endocrinol 39:4–239CrossRef
Metadaten
Titel
Effects of combined human parathyroid hormone (1–34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats
verfasst von
Hang Li
Qiang Zhou
Bing-Li Bai
She-Ji Weng
Zong-Yi Wu
Zhong-Jie Xie
Zhen-Hua Feng
Liang Cheng
Viraj Boodhun
Lei Yang
Publikationsdatum
26.12.2017
Verlag
Springer Japan
Erschienen in
Journal of Bone and Mineral Metabolism / Ausgabe 6/2018
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-017-0893-9

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