nach oben

Osteoporosis International

Erschienen in:

01.03.2015 | Original Article

Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials

verfasst von: Z.-B. Huang, S.-L. Wan, Y.-J. Lu, L. Ning, C. Liu, S.-W. Fan

Erschienen in: Osteoporosis International | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Summary

To identify the role of vitamin K2 for the prevention and treatment of osteoporosis in postmenopausal women, we conducted this meta-analysis of 19 randomized controlled trials. Our results showed that vitamin K2 might play a role in maintaining the bone mineral density and in reducing the incidence of fractures for postmenopausal women with osteoporosis.

Introduction

Vitamin K2 has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, which was not confirmed in western countries. Thus, we conduct this meta-analysis to verify the hypothesis that vitamin K2 plays a role in the prevention and treatment of osteoporosis for postmenopausal women.

Methods

We searched the Cochrane Library, Pub Med, EMBASE, and ISI web of knowledge (until December 1, 2013) and reference lists of eligible articles. A meta-analysis of all-including randomized controlled trials was then performed.

Results

Nineteen randomized controlled trials encompassing 6759 participants have met the inclusion criteria. Subgroup analysis of postmenopausal women with osteoporosis revealed a significant improvement of vertebral BMD for both medium-term and long-term results favoring vitamin K2 group (p < 0.00001 and p = 0.0005). However, no significant difference in BMD changes was revealed for the non-osteoporosis subgroup analysis. As for the incidence of fractures, pooled analysis of the seven related studies demonstrated no significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.63, p = 0.08). However, sensitivity analysis by rejecting the study inducing heterogeneity demonstrated a significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.50, p = 0.0005). Significant differences were found in undercarboxylated osteocalcin reduction and osteocalcin increment. The result of adverse reaction analysis showed that vitamin K2 group seemed to have a higher adverse reaction rate (RR = 1.22, p = 0.06).

Conclusions

This meta-analysis seemed to support the hypothesis that vitamin K2 plays kind of a role in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. The reduction of undercarboxylated osteocalcin and increment of osteocalcin may have some relation to the process of bone mineralization. However, the effect of vitamin K2 for postmenopausal women without osteoporosis had not been identified. Further high-quality RCTs with large sample size are needed to confirm the role of vitamin K2 in osteoporosis for postmenopausal women.

National Osteoporosis Foundation. Fast facts. http://www.nof.org/connect/get-the-facts. Accessed 24 Jan (2014)

Meunier PJ, Roux C, Ortolani S et al (2009) Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20:1663–1673CrossRefPubMedCentralPubMed

Meunier PJ, Roux C, Seeman E et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468CrossRefPubMed

Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026CrossRefPubMed

Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441CrossRefPubMed

McClung MR, Geusens P, Miller PD, Hip Intervention Program Study Group et al (2001) Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 344:333–340CrossRefPubMed

Black DM, Cummings SR, Karpf DB, Fracture Intervention Trial Research Group et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541CrossRefPubMed

Suttie JW (2009) Vitamin K in health and disease. Chapter 5:93–132

Kaneki M, Hodges SJ, Hosoi T et al (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 17:315–321CrossRefPubMed

10.

Yamaguchi M, Kakuda H, Gao YH, 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 18:71–76CrossRefPubMed

11.

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 15:515–521CrossRefPubMed

12.

Mawatari T, Miura H, 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 15:1810–1817CrossRefPubMed

13.

Iwamoto I, Kosha S, Noguchi S, 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 31:161–164CrossRefPubMed

14.

Tasci AG, Bilgili H, Altunay H, Gecit MR, Keskin D (2011) Prospective evaluation of vitamin K2, raloxifene and their co-administration in osteoporotic rats. Eur J Pharm Sci 43:270–277CrossRefPubMed

15.

Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed

16.

Urayama S, Kawakami A, Nakashima T et al (2000) Effect of vitamin K2 on osteoblast apoptosis: vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine. J Lab Clin Med 136:181–193CrossRefPubMed

17.

Ichikawa T, Horie-Inoue 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 39:239–247CrossRefPubMed

18.

Iwamoto J, Takeda T, Ichimura S (2000) Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci 5:546–551CrossRefPubMed

19.

Iwamoto J, Takeda T, Ichimura S (2001) Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J Orthop Sci 6:487–492CrossRefPubMed

20.

Ishida Y, Kawai S (2004) Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: the Yamaguchi Osteoporosis Prevention Study. Am J Med 117:549–555CrossRefPubMed

21.

Orimo H, Shiraki M, Tomita A, Morii H, Fujita T, Ohata M (1998) Effects of menatetrenone on the bone and calcium metabolism in osteoporosis: a double-blind placebo-controlled study. J Bone Miner Metab 16:106–112CrossRef

22.

Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2010) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–1740CrossRefPubMed

23.

Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res 24:983–991CrossRefPubMedCentralPubMed

24.

Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–1261CrossRefPubMed

25.

Iwamoto J, Matsumoto H, Takeda T (2009) Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials. Clin Drug Investig 29:471–479CrossRefPubMed

26.

Fang Y, Hu C, Tao X, Wan Y, Tao F (2012) Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Miner Metab 30:60–68CrossRefPubMed

27.

Furlan AD, Pennick V, Bombardier C, van Tulder M (2009) 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine (Phila Pa 1976) 34:1929–1941CrossRef

28.

Higgins JPT DJe Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org

29.

Higgins JPT DJ, Altman DG (editors). Chapter 16: special topics in statistics. In: Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org

30.

Koitaya N, Sekiguchi M, Tousen Y et al (2013) Low-dose vitamin K (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab 24:24

31.

Kasukawa Y, Miyakoshi N, Ebina T, Aizawa T, Hongo M, Nozaka K, Ishikawa Y, Saito H, Chida S, Shimada Y (2013) Effects of risedronate alone or combined with vitamin K on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis. J Bone Miner Metab 12:12

32.

Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y (2012) Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II. Calcif Tissue Int 90:251–262CrossRefPubMed

33.

Moschonis G, Kanellakis S, Papaioannou N, Schaafsma A, Manios Y (2011) Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II. J Bone Miner Metab 29:501–506CrossRefPubMed

34.

Je SH, Joo NS, Choi BH, Kim KM, Kim BT, Park SB, Cho DY, Kyu-nam-Kim LDJ (2011) Vitamin K supplement along with vitamin d and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old. J Korean Med Sci 26:1093–1098CrossRefPubMedCentralPubMed

35.

Shiraki M, Itabashi A (2009) Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. J Bone Miner Metab 27:333–340CrossRefPubMed

36.

Inoue T, Fujita T, Kishimoto H, Makino 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 27:66–75CrossRefPubMed

37.

Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H (2008) Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab 26:260–264CrossRefPubMed

38.

Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963–972CrossRefPubMedCentralPubMed

39.

Purwosunu Y, Muharram RIA, Reksoprodjo S, Sekizawa A (2006) Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res 32:230–234CrossRefPubMed

40.

Ushiroyama T, Ikeda A, Ueki M (2002) Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas 41:211–221CrossRefPubMed

41.

Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E (2013) Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int 24:2499–2507CrossRefPubMed

42.

Stevenson M, Lloyd-Jones M, Papaioannou D (2009) Vitamin K to prevent fractures in older women: systematic review and economic evaluation. Health Technol Assess 13:1–134CrossRefPubMed

43.

Iwamoto J, Takeda T, Sato Y (2006) Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Curr Drug Saf 1:87–97CrossRefPubMed

44.

Yamauchi M, Yamaguchi T, Nawata K, Takaoka S, Sugimoto T (2010) Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women. Clin Nutr 29:761–765CrossRefPubMed

Titel: Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials
verfasst von: Z.-B. Huang
S.-L. Wan
Y.-J. Lu
L. Ning
C. Liu
S.-W. Fan
Publikationsdatum: 01.03.2015
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 3/2015
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2989-6

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2015

Trends in fall-related hospitalisations in older people living in aged care facilities

Increased undercarboxylated osteocalcin/intact osteocalcin ratio in patients undergoing hemodialysis

Relationship between American Society of Anesthesiologists (ASA) grade and 1-year mortality in nonagenarians undergoing hip fracture surgery

Changes in skeletal collagen cross-links and matrix hydration in high- and low-turnover chronic kidney disease

Wintertime surgery increases the risk of conversion to hip arthroplasty after internal fixation of femoral neck fracture