Osteoporosis International

, Volume 19, Issue 8, pp 1153–1160 | Cite as

Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women

  • P. D. Delmas
  • S. R. Davis
  • J. Hensen
  • S. Adami
  • S. van Os
  • E. A. Nijland
Original Article



A randomized trial was conducted in osteopenic postmenopausal women to compare the efficacy of tibolone versus raloxifene on BMD of the lumbar spine and hip. Tibolone increased lumbar spine and total hip BMD to a statistically significantly greater extent than raloxifene after two years of treatment.


Both tibolone, a selective tissue estrogenic activity regulator (STEAR), and raloxifene, a selective estrogen receptor modulator (SERM), are known to prevent postmenopausal bone loss. However, no head-to-head studies to compare the efficacy on bone have been performed.


A double-blind, randomized trial was conducted in osteopenic postmenopausal women aged 60–79 years to compare the effects of tibolone 1.25 mg/day to raloxifene 60 mg/day on bone mineral density (BMD). Serum osteocalcin and serum type I collagen C-telopeptides were measured as biochemical markers of bone metabolism.


Three hundred and eight subjects were allocated to treatment. Both treatments significantly increased lumbar spine BMD, however the increase was significantly larger after tibolone treatment than after raloxifene treatment (at year 1: 2.2% versus 1.2%, p < 0.01 and at year 2: 3.8% versus 2.1%, p < 0.001). After 2 years of treatment, the increase in total hip BMD in the tibolone group was significantly larger than in the raloxifene group (p < 0.05). Both treatments significantly reduced type I collagen C-telopeptides and osteocalcin levels when compared to baseline.


Tibolone 1.25 mg/day for 2 years prevents postmenopausal bone loss in older women and results in a larger increase of BMD both at the lumbar spine and hip than raloxifene.


Bone mineral density Menopause Osteoporosis Raloxifene Tibolone 



The authors would like to thank Ellemiek von Mauw (Global Clinical Development, Organon, Oss) and Sabine Braat (Biometrics Department, Organon, Oss) for their contributions to the execution, statistical analysis and reporting of this study. The editorial contribution of Jane Irons (JSI Communications) to this manuscript is also acknowledged.

Conflicts of interest

P. Delmas has consulted for and received speaker fees from Organon. E. Nijland was an employee of Organon at the time of the study. S. Davis has been an investigator for Organon and has received honoraria for lectures from Organon. S. Adami and J. Hensen report no relevant conflicts of interest.

Funding source

This study was funded by NV Organon, Oss, The Netherlands.

Manufacturer names

Tibolone (Livial®): NV Organon

Raloxifene (Evista®): Eli Lilly


  1. 1.
    European Foundation for Osteoporosis and the National Osteoporosis Foundation (1997) Consensus Development Statement: Who are candidates for prevention and treatment for osteoporosis? Osteoporos Int 7:1–6Google Scholar
  2. 2.
    Melton LJ 3rd, Chrischilles EA, Cooper C et al (1992) Perspective.How many women have osteoporosis? J Bone Miner Res 7:1005–1010PubMedCrossRefGoogle Scholar
  3. 3.
    Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767PubMedCrossRefGoogle Scholar
  4. 4.
    Leibson CL, Tosteson AN, Gabriel SE et al (2002) Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 50:1644–1650PubMedCrossRefGoogle Scholar
  5. 5.
    Wells G, Tugwell P, Shea B et al, for the Osteoporosis Methodology Group and the Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 23:529–539PubMedCrossRefGoogle Scholar
  6. 6.
    Cauley JA, Robbins J, Chen Z et al, for the Women’s Health Initiative Investigators (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290:1729–1738PubMedCrossRefGoogle Scholar
  7. 7.
    Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333CrossRefGoogle Scholar
  8. 8.
    Kloosterboer HJ (2004) Tissue-selectivity: the mechanism of action of tibolone. Maturitas 48(Suppl 1):S30–S40PubMedCrossRefGoogle Scholar
  9. 9.
    Ederveen AGH, Kloosterboer HJ (2001) Tibolone exerts its protective effect on trabecular bone loss through the estrogen receptor. J Bone Miner Res 16:1651–1657PubMedCrossRefGoogle Scholar
  10. 10.
    Thiebaud D, Bigler JM, Renteria S et al. A 3-year study of prevention of postmenopausal bone loss: conjugated estrogens plus medroxyprogesterone acetate versus tibolone. Climacteric 1:202–210Google Scholar
  11. 11.
    Roux C, Pelissier C, Fechtenbaum J et al (2002) Randomized, double-blind, 2-year comparison of tibolone with 17β-estradiol and norethindrone acetate in preventing postmenopausal bone loss. Osteoporosis Int 13:241–248CrossRefGoogle Scholar
  12. 12.
    Lippuner K, Haenggi W, Birkhaeuser MH et al (1997) Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17β-oestradiol and dydrogesterone. J Bone Miner Res 12:806–812PubMedCrossRefGoogle Scholar
  13. 13.
    Milner M, Harrison RF, Gilligan E et al (2000) Bone density changes during two years treatment with tibolone or conjugated estrogens and norgestrel, compared with untreated controls in postmenopausal women. Menopause 7:327–333PubMedCrossRefGoogle Scholar
  14. 14.
    Rymer J, Robinson J, Fogelman I (2002) Ten years of treatment with tibolone 2.5 mg daily: effects on bone loss in postmenopausal women. Climacteric 5:390–398PubMedCrossRefGoogle Scholar
  15. 15.
    Berning B, Kuijk CV, Kuiper JW et al (1996) Effects of two doses of tibolone on trabecular and cortical bone loss in early postmenopausal women: a two-year randomized, placebo-controlled study. Bone 19:395–399PubMedCrossRefGoogle Scholar
  16. 16.
    Pavlov PW, Ginsburg J, Kicovic PM et al (1999) Double-blind, placebo controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures. Gynecol Endocrinol 13:230–237PubMedCrossRefGoogle Scholar
  17. 17.
    Bjarnason NH, Bjarnason K, Haarbo J et al (1996) Tibolone prevention of bone loss in late postmenopausal women. J Clin Endocronol Metab 81:2419–2422CrossRefGoogle Scholar
  18. 18.
    Bjarnason BH, Bjarnason K, Hassager C et al (1997) The response in spinal bone mass to tibolone treatment is related to bone turnover in elderly women. Bone 20:151–155PubMedCrossRefGoogle Scholar
  19. 19.
    Gallagher JC, Baylink DJ, Freeman R et al (2001) Prevention of bone loss with tibolone in postmenopausal women: results of two randomized, double-blind, placebo-controlled, dose-finding studies. J Clin Endocrinol Metab 86:4717–4726PubMedCrossRefGoogle Scholar
  20. 20.
    Gambacciani M, Ciaponi M, Cappagli B et al (2004) A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women. Gynecol Endocrinol 18:9–16PubMedCrossRefGoogle Scholar
  21. 21.
    Delmas PD, Bjarnason NH, Mitlak BH et al (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337:1641–1647PubMedCrossRefGoogle Scholar
  22. 22.
    Weinstein RS, Parfitt AM, Marcus R et al (2003) Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women. Osteoporos Int 14:814–822PubMedCrossRefGoogle Scholar
  23. 23.
    Lufkin EG, Whitaker MD, Nickelsen T et al (1998) Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 13:1747–1754PubMedCrossRefGoogle Scholar
  24. 24.
    Johnston CC Jr, Bjarnason NH, Cohen FJ et al (2000) Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials. Arch Intern Med 160:3444–3450PubMedCrossRefGoogle Scholar
  25. 25.
    Meunier PJ, Vignot E, Garnero P et al (1999) Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group. Osteoporos Int 10:330–336PubMedCrossRefGoogle Scholar
  26. 26.
    Ettinger B, Black DM, Mitlak BH et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645PubMedCrossRefGoogle Scholar
  27. 27.
    Delmas PD, Ensrud KE, Adachi JD et al, for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators (2002) Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87:3609–3617PubMedCrossRefGoogle Scholar
  28. 28.
    Cummings SR, Delmas PD, Bilezikian JP et al (2006) The effects of tibolone in older women with osteoporosis: preliminary results from the LIFT trial. Osteoporos Int 17:952–953Google Scholar
  29. 29.
    Cummings SR (2006) LIFT study is discontinued. Letter to the editor. BMJ 332:667PubMedCrossRefGoogle Scholar
  30. 30.
    The North American Menopause Society (2006) Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 13:340–367CrossRefGoogle Scholar
  31. 31.
    Studd J, Arnala I, Kicovic PM et al (1998) A randomized study of tibolone on bone mineral density in osteoporotic postmenopausal women with previous fractures. Obstet Gynecol 92:574–579PubMedCrossRefGoogle Scholar
  32. 32.
    Geusens P, Dequeker J, Gielen J et al (1991) Non-linear increase in vertebral density induced by a synthetic steroid (org OD14) in women with established osteoporosis. Maturitas 13:155–162PubMedCrossRefGoogle Scholar
  33. 33.
    Dören M, Nilsson J-Å, Johnell O (2003) Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis. Hum Reprod 18:1737–1746PubMedCrossRefGoogle Scholar
  34. 34.
    Siris ES, Harris ST, Eastell R et al, for the Continuing Outcomes Relevant to Evista (CORE) Investigators (2005) Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res 20:1514–1524PubMedCrossRefGoogle Scholar
  35. 35.
    Delmas PD, Genant HK, Crans GG et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRefGoogle Scholar
  36. 36.
    Frolik CA, Bryant HU, Black EC et al (1996) Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen and alendronate. Bone 18:621–627PubMedCrossRefGoogle Scholar
  37. 37.
    Heaney RP, Draper MW (1997) Raloxifene and estrogen: comparative bone-remodeling kinetics. J Clin Endocrinol Metab 82:3425–3429PubMedCrossRefGoogle Scholar
  38. 38.
    Kloosterboer HJ, Ederveen AGH (2003) Pros and cons of existing treatment modalities in osteoporosis: a comparison between tibolone, SERMs and estrogen (±progestogen) treatments. J Steroid Biochem Mol Biol 83:157–165CrossRefGoogle Scholar
  39. 39.
    Allen MR, Iwata K, Sato M et al (2006) Raloxifene enhances vertebral mechanical properties independent of bone density. Bone 39:1130–1135PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • P. D. Delmas
    • 1
    • 7
  • S. R. Davis
    • 2
  • J. Hensen
    • 3
  • S. Adami
    • 4
  • S. van Os
    • 5
  • E. A. Nijland
    • 6
  1. 1.INSERM Research Unit 831 and University of LyonLyonFrance
  2. 2.Monash Medical SchoolPrahranAustralia
  3. 3.University of ErlangenErlangenGermany
  4. 4.University of VeronaValeggio sul MincioItaly
  5. 5.Global Clinical Development, NV OrganonOssThe Netherlands
  6. 6.Rugpoli TwenteDeldenThe Netherlands
  7. 7.INSERM Research Unit 831, Hôpital E. HerriotLyonFrance

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