Advertisement

Journal of Bone and Mineral Metabolism

, Volume 36, Issue 2, pp 221–228 | Cite as

Effect of osteoporosis medication on changes in bone mineral density and bone turnover markers after 24-month administration of daily teriparatide: comparison among minodronate, raloxifene, and eldecalcitol

  • Shinichi NakatohEmail author
Original Article

Abstract

This study reveals the changes in bone mineral density (BMD), the turnover rate, and the balance [multiple of median formation/multiple of median resorption (MoMf/MoMr)] affected by the selection of different bone resorption inhibitors after 24-month daily teriparatide (20 µg/day) administration. The turnover rate was calculated as √(MoMf2 + MoMr2), where MoMf = bone-specific alkaline phosphatase (BAP) value/18.6 and MoMr = tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463. One hundred and twenty-one osteoporotic women (mean age 82.4 years) were randomly administered minodronate (50 mg/28 days), raloxifene (60 mg/day), or eldecalcitol (0.75 µg/day) after teriparatide discontinuation. BMD was measured at 0, 24, and 48 weeks; BAP values and TRACP-5b were measured at 0, 12, 24, 36, and 48 weeks after administration of bone resorption inhibitors. In the minodronate group, BMD increased significantly from week 0 to weeks 24 and 48. The turnover rate was significantly reduced at week 12, and remained so over the entire course in all three groups. The speed of change of turnover rate was greatest in the minodronate group. The balance in the minodronate group shifted significantly toward formation dominance at week 12 (to 0.97 from 0.87) and then again toward resorption dominance (to 0.84) at week 24. However, no further advancement in resorption dominance was observed until week 48. Conversely, the balance in the raloxifene and eldecalcitol groups shifted toward resorption dominance gradually over the entire course. In conclusion, the BMD-increasing effect was greatest with minodronate administration and depends not only on the decrease in turnover rate but also on changes in balance after teriparatide discontinuation.

Keywords

Osteoporosis Teriparatide Minodronate Bone mineral density Bone turnover markers 

Notes

Compliance with ethical standards

Conflict of interest

This study was planned as an investigator-initiated study, and necessary costs were supported by a research grant from Astellas Pharma.

References

  1. 1.
    Yamamoto T, Taketsuna M, Guo X, Sato M, Sowa H (2014) The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report. J Bone Miner Metab 32:699–708CrossRefPubMedGoogle Scholar
  2. 2.
    Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, Halse J, Lindsay R, Dalsky GP, Mitlak BH (2005) Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 20:1507–1513CrossRefPubMedGoogle Scholar
  3. 3.
    Jakob F, Oertel H, Langdahl B, Ljunggren O, Barrett A, Karras D, Walsh JB, Fahrleitner-Pammer A, Rajzbaum G, Barker C, Lems WF, Marin F (2012) Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study. Eur J Endocrinol 166:87–97CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Eastell R, Nickelsen T, Marin F, Barker C, Hadji P, Farrerons J, Audran M, Boonen S, Brixen K, Gomes JM, Obermayer-Pietsch B, Avramidis A, Sigurdsson G, Glüer CC (2009) Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J Bone Miner Res 24:726–736CrossRefPubMedGoogle Scholar
  5. 5.
    Leder BZ, Neer RM, Wyland JJ, Lee HW, Burnett-Bowie SM, Finkelstein JS (2009) Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metab 94:2915–2921CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Adami S, San Martin J, Muñoz-Torres M, Econs MJ, Xie L, Dalsky GP, McClung M, Felsenberg D, Brown JP, Brandi ML, Sipos A (2008) Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis. Randomized controlled trial. Osteoporos Int 19:87–94CrossRefPubMedGoogle Scholar
  7. 7.
    NIH consensus Development Panel on Osteoporosis Prevention (2001) Diagnosis, and therapy. JAMA 285:785–795CrossRefGoogle Scholar
  8. 8.
    Nishizawa Y, Ohta H, Miura M, Inaba M, Ichimura S, Shiraki M, Takada J, Chaki O, Hagino H, Fujiwara S, Fukunaga M, Miki T, Yoshimura N (2013) Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition). J Bone Miner Metab 31:1–15CrossRefPubMedGoogle Scholar
  9. 9.
    Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357:905–916CrossRefPubMedGoogle Scholar
  10. 10.
    Nakatoh S (2016) The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: a pilot study. J Bone Miner Metab 34:216–224CrossRefPubMedGoogle Scholar
  11. 11.
    Rubin MR, Bilezikian JP (2003) The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med 19:415–432CrossRefPubMedGoogle Scholar
  12. 12.
    Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502CrossRefPubMedGoogle Scholar
  13. 13.
    Bieglmayer C, Kudlacek S (2009) The bone marker plot: an innovative method to assess bone turnover in women. Eur J Clin Investig 39:230–238CrossRefGoogle Scholar
  14. 14.
    Soen S, Fukunaga M, Sugimoto T, Sone T, Fujiwara S, Endo N, Gorai I, Shiraki M, Hagino H, Hosoi T, Ohta H, Yoneda T, Tomomitsu T (2013) Diagnostic criteria for primary osteoporosis: year 2012 revision. J Bone Miner Metab 31:247–257CrossRefPubMedGoogle Scholar
  15. 15.
    Barrett-Connor E, Weiss TW, McHorney CA, Miller PD, Siris ES (2009) Predictors of falls among postmenopausal women: result from the National Osteoporosis Risk Assessment (NORA). Osteoporos Int 20:715–722CrossRefPubMedGoogle Scholar
  16. 16.
    Nakatoh S (2014) Utility of calculations bone turnover rates and bone formation/resorption ratios in osteoporosis care (in Japanese). Osteoporos Jpn 22:133–140Google Scholar
  17. 17.
    Panico A, Lupoli GA, Marciello F, Lupoli R, Cacciapuoti M, Martinelli A, Granieri L, Iacono D, Lupoli G (2011) Teriparatide vs. alendronate as a treatment for osteoporosis: changes in biochemical markers of bone turnover, BMD and quality of life. Med Sci Monit 17:CR442–CR448CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Muschitz C, Kocijan R, Fahrleitner-Pammer A, Pavo I, Haschka J, Schima W, Kapiotis S, Resch H (2014) Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density—the CONFORS Study. J Bone Miner Res 29:1777–1785CrossRefPubMedGoogle Scholar
  19. 19.
    Ebina K, Hashimoto J, Kashii M, Hirao M, Kaneshiro S, Noguchi T, Tsukamoto Y, Yoshikawa H (2017) The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis. J Bone Miner Metab 35:91–98CrossRefPubMedGoogle Scholar
  20. 20.
    Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242PubMedGoogle Scholar
  21. 21.
    Fleisch H (2000) Bisphosphonates in bone disease. Academic Press, San DiegoGoogle Scholar
  22. 22.
    Matsumoto T, Hagino H, Shiraki M, Fukunaga M, Nakano T, Takaoka K, Morii H, Ohashi Y, Nakamura T (2009) Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study. Osteoporos Int 20:1429–1437CrossRefPubMedGoogle Scholar
  23. 23.
    Morii H, Ohashi Y, Taketani Y, Fukunaga M, Nakamura T, Itabashi A, Sarkar S, Harper K (2003) Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial. Osteoporos Int 14:793–800CrossRefPubMedGoogle Scholar
  24. 24.
    Matsumoto T, Ito M, Hayashi Y, Hirota T, Tanigawara Y, Sone T, Fukunaga M, Shiraki M, Nakamura T (2011) A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures—a randomized, active comparator, double-blind study. Bone 49:605–612CrossRefPubMedGoogle Scholar
  25. 25.
    Hagino H, Shiraki M, Fukunaga M, Nakano T, Takaoka K, Ohashi Y, Nakamura T, Matsumoto T (2012) Three years of treatment with minodronate in patients with postmenopausal osteoporosis. J Bone Miner Metab 30:439–446CrossRefPubMedGoogle Scholar
  26. 26.
    Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184CrossRefPubMedGoogle Scholar
  27. 27.
    Díez-Pérez A, Olmos JM, Nogués X, Sosa M, Díaz-Curiel M, Pérez-Castrillón JL, Pérez-Cano R, Muñoz-Torres M, Torrijos A, Jodar E, Del Rio L, Caeiro-Rey JR, Farrerons J, Vila J, Arnaud C, González-Macías J (2012) Risk factors for prediction of inadequate response to antiresorptives. J Bone Miner Res 27:817–824CrossRefPubMedGoogle Scholar
  28. 28.
    Matsumoto T, Kubodera N (2007) ED-71, a new active vitamin D3, increases bone mineral density regardless of serum 25(OH)D levels in osteoporotic subjects. J Steroid Biochem Mol Biol 103:584–586CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2017

Authors and Affiliations

  1. 1.Department of Orthopedic SurgeryAsahi General HospitalToyamaJapan

Personalised recommendations