Skip to main content

Advertisement

SpringerLink
Log in

Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment

  • Short Communication
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this study, serum activin-A was increased in postmenopausal women with low bone mass and was positively correlated to age and negatively to lumbar spinal bone mineral density (BMD). Serum activin-A levels did not change 3 months after zoledronic acid infusion.

Introduction

The aims of the study were to evaluate prospectively the circulating activin-A levels in postmenopausal women with low bone mass and explore possible correlations with clinical and laboratory data, as well as the 3-month effect of zoledronic acid infusion.

Methods

Postmenopausal women with low bone mass assigned to receive zoledronic acid infusion (Patients, n = 47) and age-matched, postmenopausal women with normal bone mass (Controls, n = 27) were recruited on an outpatient basis. Main outcome measurement was serum activin-A levels.

Results

Serum activin-A was higher in patients at baseline compared to controls (p < 0.001) and activin-A in the serum of patients and controls was positively correlated with age (Spearman’s coefficient of correlation [rs] = 0.325; p = 0.005) and negatively with lumbar spinal (LS) BMD (rs = −0.425; p < 0.001). In multiple linear regression analysis, only age (B = 8.93; 95 % CI = 4.39–13.46; p < 0.001) was associated with serum activin-A levels at baseline, independent from group (patients or controls), previous anti-osteoporotic treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels were not affected 3 months after zoledronic acid infusion.

Conclusions

Serum activin-A is increased in postmenopausal women with low bone mass compared with postmenopausal women with normal bone mass and is positively correlated to age and negatively to LS BMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. de Kretser DM, O'Hehir RE, Hardy CL, Hedger MP (2012) The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Mol Cell Endocrinol 359:101–106

    Article  PubMed  Google Scholar 

  2. Payne C, King J, Hay D (2011) The role of activin/nodal and Wnt signaling in endoderm formation. Vitam Horm 85:207–216

    Article  PubMed  CAS  Google Scholar 

  3. Luisi S, Florio P, Reis FM, Petraglia F (2001) Expression and secretion of activin A: possible physiological and clinical implications. Eur J Endocrinol 145:225–236

    Article  PubMed  CAS  Google Scholar 

  4. Toulis KA, Anastasilakis AD, Polyzos S, Makras P (2011) Targeting the osteoblast: approved and experimental anabolic agents for the treatment of osteoporosis. Hormones (Athens) 10:174–195

    Google Scholar 

  5. Eijken M, Swagemakers S, Koedam M, Steenbergen C, Derkx P, Uitterlinden AG, van der Spek PJ, Visser JA, de Jong FH, Pols HA, van Leeuwen JP (2007) The activin A-follistatin system: potent regulator of human extracellular matrix mineralization. FASEB J 21:2949–2960

    Article  PubMed  Google Scholar 

  6. Gaddy-Kurten D, Coker JK, Abe E, Jilka RL, Manolagas SC (2002) Inhibin suppresses and activin stimulates osteoblastogenesis and osteoclastogenesis in murine bone marrow cultures. Endocrinology 143:74–83

    Article  PubMed  CAS  Google Scholar 

  7. Nicks KM, Perrien DS, Akel NS, Suva LJ, Gaddy D (2009) Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, activin and inhibin. Mol Cell Endocrinol 310:11–20

    Article  PubMed  CAS  Google Scholar 

  8. Hashimoto M, Shoda A, Inoue S, Yamada R, Kondo T, Sakurai T et al (1992) Functional regulation of osteoblastic cells by the interaction of activin-A with follistatin. J Biol Chem 267:4999–5004

    PubMed  CAS  Google Scholar 

  9. Ikenoue T, Jingushi S, Urabe K, Okazaki K, Iwamoto Y (1999) Inhibitory effects of activin-A on osteoblast differentiation during cultures of fetal rat calvarial cells. J Cell Biochem 75:206–214

    Article  PubMed  CAS  Google Scholar 

  10. Vale W, Wiater E, Gray P, Harrison C, Bilezikjian L, Choe S (2004) Activins and inhibins and their signaling. Ann N Y Acad Sci 1038:142–147

    Article  PubMed  CAS  Google Scholar 

  11. Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M, Pozzi S, Santo L, Cirstea D, Patel K, Sohani AR, Guimaraes A, Xie W, Chauhan D, Schoonmaker JA, Attar E, Churchill M, Weller E, Munshi N, Seehra J, Weissleder R, Anderson KC, Scadden DT, Raje N (2010) Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci U S A 107:5124–5129

    Article  PubMed  CAS  Google Scholar 

  12. Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, Zaidi S, Zhu L, Yaroslavskiy BB, Zhou H, Zallone A, Sairam MR, Kumar TR, Bo W, Braun J, Cardoso-Landa L, Schaffler MB, Moonga BS, Blair HC, Zaidi M (2006) FSH directly regulates bone mass. Cell 125:247–260

    Article  PubMed  CAS  Google Scholar 

  13. Terpos E, Kastritis E, Christoulas D, Gkotzamanidou M, Eleutherakis-Papaiakovou E, Kanellias N, Papatheodorou A, Dimopoulos MA (2012) Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy. Ann Oncol 23:2681–2686

    Google Scholar 

  14. Leto G (2010) Activin A and bone metastases. J Cell Physiol 225:302–309

    Article  PubMed  CAS  Google Scholar 

  15. Lotinun S, Pearsall RS, Davies MV, Marvell TH, Monnell TE, Ucran J, Fajardo RJ, Kumar R, Underwood KW, Seehra J, Bouxsein ML, Baron R (2010) A soluble activin receptor Type IIA fusion protein (ACE-011) increases bone mass via a dual anabolic-antiresorptive effect in Cynomolgus monkeys. Bone 46:1082–1088

    Article  PubMed  CAS  Google Scholar 

  16. Ruckle J, Jacobs M, Kramer W, Pearsall AE, Kumar R, Underwood KW, Seehra J, Yang Y, Condon CH, Sherman ML (2009) Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24:744–752

    Article  PubMed  CAS  Google Scholar 

  17. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661

    Article  PubMed  CAS  Google Scholar 

  18. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  Google Scholar 

  19. Drake MT, McCready LK, Hoey KA, Atkinson EJ, Khosla S (2010) Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women. J Clin Endocrinol Metab 95:5063–5068

    Article  PubMed  CAS  Google Scholar 

  20. Loots GG, Keller H, Leupin O, Murugesh D, Collette NM, Genetos DC (2012) TGF-β regulates sclerostin expression via the ECR5 enhancer. Bone 50:663–669

    Article  PubMed  CAS  Google Scholar 

  21. Fuller K, Bayley KE, Chambers TJ (2000) Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun 268:2–7

    Article  PubMed  CAS  Google Scholar 

  22. Baccarelli A, Morpurgo PS, Corsi A, Vaghi I, Fanelli M, Cremonesi G, Vaninetti S, Beck-Peccoz P, Spada A (2001) Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects. Exp Gerontol 36:1403–1412

    Article  PubMed  CAS  Google Scholar 

  23. Singhellakis PN, Malandrinou FC, Psarrou CJ, Danelli AM, Tsalavoutas SD, Constandellou ES (2011) Vitamin D deficiency in white, apparently healthy, free-living adults in a temperate region. Hormones (Athens) 10:131–143

    Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Endocrinology, 424 General Military Hospital, Ring Road, 564 29 N.Efkarpia, Thessaloniki, Greece

    A. D. Anastasilakis

  2. Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece

    S. A. Polyzos

  3. Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, Greece

    P. Makras

  4. Department of Obstetrics and Gynaecology, 424 General Military Hospital, Thessaloniki, Greece

    A. Gkiomisi

  5. 1st Department of Orthopaedics, 424 General Military Hospital, Thessaloniki, Greece

    M. Savvides

  6. Department of Medical Research, 251 General Air Force Hospital, Athens, Greece

    A. Papatheodorou

  7. Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece

    E. Terpos

Authors
  1. A. D. Anastasilakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. A. Polyzos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Makras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Gkiomisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Savvides
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Papatheodorou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Terpos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. D. Anastasilakis.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

Comparative error bars of (A) naïve patients and those having previously received other anti-osteoporotic treatment and (B) patients previously on other bisphosphonate treatment or not. Bold lines are for baseline and normal lines for month 3; BPs for bisphosphonates (JPEG 33 kb)

High resolution image (TIFF 634 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anastasilakis, A.D., Polyzos, S.A., Makras, P. et al. Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment. Osteoporos Int 24, 2127–2132 (2013). https://doi.org/10.1007/s00198-012-2198-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-2198-0

Keywords

Search

Navigation