Archives of Osteoporosis

, 14:10 | Cite as

Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial

  • Salvatore MinisolaEmail author
  • Fernando Marin
  • David L. Kendler
  • Piet Geusens
  • Cristiano A. F. Zerbini
  • Luis A. Russo
  • Enrique Casado
  • Astrid Fahrleitner-Pammer
  • Jan J. Stepan
  • Eric Lespessailles
  • Rüdiger Moericke
  • Alicia Bagur
  • Péter Lakatos
  • Pedro López-Romero
  • Jean Jacques Body
Short Scientific Communication



Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category.


Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 μg or oral weekly risedronate 35 mg, with concomitant 500–1000 mg of elemental calcium and 400–800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients. Heterogeneity of the treatment effect on fractures was investigated by logistic and Cox proportional hazards regression models.


At baseline, mean serum 25(OH)D was 31.9 ng/mL in the teriparatide group and 31.5 ng/mL in the risedronate group, and 16.8% and 17.9% of patients, respectively, were 25(OH)D insufficient. At month 6, the mean serum 25(OH)D concentration decreased in teriparatide-treated patients to 24.5 ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2 ng/mL) (p < 0.001). Proportions of 25(OH)D insufficient patients at month 6 were 26.7% and 5.6%, respectively (p < 0.001). The risk reduction with teriparatide versus risedronate for any of the fracture endpoints did not significantly differ between subgroups by 25(OH)D sufficiency status at baseline, with nonsignificant (p > 0.1) treatment-by-25(OH)D interactions in all fracture analyses.


Serum 25(OH)D concentration decreases during teriparatide treatment. Fracture risk reduction with teriparatide versus risedronate did not significantly differ between the two groups of patients defined by baseline 25(OH)D.

Trial registration Identifier: NCT01709110

EudraCT Number: 2012-000123-41


Teriparatide Fractures Postmenopausal osteoporosis 25-Hydroxy-vitamin D Subgroup analysis Bisphosphonates 



We are indebted to Anja Gentzel-Jorczyk (Clinical Trial Coordinator), and Estrella Crespo and Laura Briones (Data Management) for their contribution to the study, to Ansgar Dressler and Bhawna Basin from Trilogy Writing and Consulting for editorial assistance, to the members of the investigational teams at the study centers, and to the women who participated in the study.


This VERO clinical trial was funded by Lilly.

Compliance with ethical standards

Conflicts of interest

Salvatore Minisola: Speaker and/or consultant fees from: Abiogen, Amgen, DiaSorin, Lilly, Italfarmaco, Fujii, MSD, Takeda. Fernando Marin: Lilly Employee. David L. Kendler: Honoraria, research grants, and/or consultant fees from: Amgen, Lilly, AstraZeneca, Astellas, UCB. Piet Geusens: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis. Cristiano A.F. Zerbini: Research support from Lilly. Luis A. Russo: None. Enrique Casado: Speaker fees from: Amgen, Lilly. Astrid Fahrleitner-Pammer: Speaker fees from: Amgen, Alexion, BMS, Lilly, Fresenius. Jan J. Stepan: None. Eric Lespessailles: Speaker and consultant fees from: Amgen, Expanscience, Lilly, MSD; research grants from Abbvie, Amgen, Lilly, MSD, UCB. Rüdiger Möricke: None. Alicia Bagur: Speaker fees from Lilly and Craveri. Péter Lakatos: None. Pedro López-Romero: Lilly Employee. Jean Jacques Body: Speaker fee from Amgen; research support from Lilly.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, Bagur A, Malouf-Sierra J, Lakatos P, Fahrleitner-Pammer A, Lespessailles E, Minisola S, Body JJ, Geusens P, Möricke R, López-Romero P (2018) Effects of teriparatide and risedronate on new fractures in postmenopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 391:230–240. CrossRefPubMedGoogle Scholar
  2. 2.
    Geusens P, Marin F, Kendler DL, Russo LA, Zerbini CAF, Minisola S, Body JJ, Lespessailles E, Greenspan SL, Bagur A, Stepan JJ, Lakatos P, Casado E, Moericke R, López-Romero P, Fahrleitner-Pammer A (2018) Effects of teriparatide compared with risedronate on the risk of fractures in subgroups of postmenopausal women with severe osteoporosis: the VERO trial. J Bone Miner Res 33(5):783–794. CrossRefPubMedGoogle Scholar
  3. 3.
    Dawson-Hughes B, Chen P, Krege JH (2007) Response to teriparatide in patients with baseline 25-hydroxyvitamin D insufficiency or sufficiency. J Clin Endocrinol Metab 92(12):4630–4636. CrossRefPubMedGoogle Scholar
  4. 4.
    Cosman F, Dawson-Hughes B, Wan X, Krege JH (2012) Changes in vitamin D metabolites during teriparatide treatment. Bone 50(6):1368–1371. CrossRefPubMedGoogle Scholar
  5. 5.
    Mok J, Brown C, Moore AEB, Min SS, Hampson G (2018) Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in post-menopausal women with osteoporosis and a high prevalence of secondary risk factors in real-life setting of a metabolic bone clinic; effect of age and vitamin D status. Endocr Res 13:1–8. CrossRefGoogle Scholar
  6. 6.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8(9):1137–1148. CrossRefPubMedGoogle Scholar
  7. 7.
    Institute of Medicine (US) Committee to review dietary reference intakes for vitamin D and calcium (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington DC, pp 260–262Google Scholar
  8. 8.
    Cauley JA, Greendale GA, Ruppert K, Lian Y, Randolph JF Jr, Lo JC, Burnett-Bowie SA, Finkelstein JS (2015) Serum 25 hydroxyvitamin D, bone mineral density and fracture risk across the menopause. J Clin Endocrinol Metab 100(5):2046–2054. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Licata AA (2005) Osteoporosis, teriparatide, and dosing of calcium and vitamin D. N Engl J Med 352(18):1930–1931. CrossRefPubMedGoogle Scholar
  10. 10.
    Sridharan M, Cheung J, Moore AE, Frost ML, Fraser WD, Fogelman I, Hampson G (2010) Circulating fibroblast growth factor-23 increases following intermittent parathyroid hormone (1-34) in postmenopausal osteoporosis: association with biomarker of bone formation. Calcif Tissue Int 87(5):398–405. CrossRefPubMedGoogle Scholar
  11. 11.
    Alshayeb H, Showkat A, Wall BM, Gyamlani GG, David V, Quarles LD (2014) Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol. J Clin Endocrinol Metab 99(10):E1830–E1837. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ginsberg C, Katz R, de Boer IH, Kestenbaum BR, Chonchol M, Shlipak MG, Sarnak MJ, Hoofnagle AN, Rifkin DE, Garimella PS, Ix JH (2018) The 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: the cardiovascular health study. Bone 107:124–130. CrossRefPubMedGoogle Scholar
  13. 13.
    Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26(7):1609–1616. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Van Schoor NM, Visser M, Pluijm SM, Kuchuk N, Smit JH, Lips P (2008) Vitamin D deficiency as a risk factor for osteoporotic fractures. Bone 42(2):260–266. CrossRefPubMedGoogle Scholar
  15. 15.
    Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA study of elderly women. Osteoporos Int 16(11):1425–1431. CrossRefPubMedGoogle Scholar
  16. 16.
    Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of osteoporotic fractures research group. N Engl J Med 339(11):733–738. CrossRefPubMedGoogle Scholar
  17. 17.
    Garnero P, Munoz F, Sornay-Rendu E, Delmas PD (2007) Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone 40(3):716–722. CrossRefPubMedGoogle Scholar
  18. 18.
    Roddam AW, Neale R, Appleby P, Allen NE, Tipper S, Key TJ (2007) Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Am J Epidemiol 166(11):1327–1336. CrossRefPubMedGoogle Scholar
  19. 19.
    Looker AC, Mussolino ME (2008) Serum 25-hydroxyvitamin D and hip fracture risk in older U.S. white adults. J Bone Miner Res 23(1):143–150. CrossRefPubMedGoogle Scholar
  20. 20.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930. CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  • Salvatore Minisola
    • 1
    Email author
  • Fernando Marin
    • 2
  • David L. Kendler
    • 3
  • Piet Geusens
    • 4
  • Cristiano A. F. Zerbini
    • 5
  • Luis A. Russo
    • 6
  • Enrique Casado
    • 7
  • Astrid Fahrleitner-Pammer
    • 8
  • Jan J. Stepan
    • 9
  • Eric Lespessailles
    • 10
  • Rüdiger Moericke
    • 11
  • Alicia Bagur
    • 12
  • Péter Lakatos
    • 13
  • Pedro López-Romero
    • 2
  • Jean Jacques Body
    • 14
  1. 1.Department of Internal Medicine and Medical DisciplinesSapienza Rome UniversityRomeItaly
  2. 2.Lilly Research Center EuropeMadridSpain
  3. 3.University of British ColumbiaVancouverCanada
  4. 4.Maastricht University Medical CenterMaastrichtThe Netherlands
  5. 5.Centro Paulista de Investigaçao ClínicaSao PauloBrazil
  6. 6.Centro de Analises e Pesquisas Clínicas LTDARio de JaneiroBrazil
  7. 7.University Hospital Parc Taulí Sabadell (UAB)BarcelonaSpain
  8. 8.Division of Endocrinology and DiabetologyMedical University of GrazGrazAustria
  9. 9.Institute of Rheumatology and Faculty of Medicine 1Charles UniversityPragueCzech Republic
  10. 10.Regional HospitalUniversity of OrleansOrleansFrance
  11. 11.Institut Präventive Medizin & Klinische ForschungMagdeburgGermany
  12. 12.Centro de Osteopatías ComlitBuenos AiresArgentina
  13. 13.Semmelweis University Medical SchoolBudapestHungary
  14. 14.CHU BrugmannULBBrusselsBelgium

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