Nandrolone decanoate in induced fracture nonunion with vascular deficit in rat model: morphological aspects

  • R. SenosEmail author
  • M. Roberto-Rodrigues
  • R. M. P. Fernandes
  • T. M. P. Santos
  • L. P. Viana
  • I. Lima
  • M. A. Guzman-Silva
  • M. S. Gomes
  • R. E. G. Rici
  • J. R. Kfoury Júnior
Original Article



The nonunion fracture is a relatively frequent complication in both human and veterinary medicine. Specifically, atrophic fracture nonunions are difficult to treat, with revision surgery usually providing the best prognosis. Anabolic steroids, such as nandrolone decanoate (ND), have been reported to have beneficial clinical effects on bone mass gain during osteoporosis; however, their utility in promoting regeneration in atrophic nonunions has not been documented. Our objective was to examine morphological changes induced by the ND in experimental fracture nonunion with vascular deficit in the rat model.


Fourteen adult Wistar rats had an atrophic fracture nonunion induced in the diaphysis of their left femur. Rats were allocated into two groups: control group and nandrolone decanoate group. Rats in the latter group were given nandrolone decanoate (1.5 mg/kg IM, once a week, during 4 weeks after confirmation of fracture nonunion radiographically). Radiographic and anatomopathological examination, micro-tomography and histological analysis were assessed to characterize the morphological changes promoted by the nandrolone decanoate use.


Based on radiology, anatomopathological evaluation, computed micro-tomography and conventional microscopy, nandrolone decanoate promoted bone regeneration at the fracture nonunion site by increasing the cellularity at the fracture site. Percentage of collagen was not significantly different between groups, consistent with high-quality regenerated bone.


The anabolic steroid nandrolone decanoate improved bone mass and regeneration without affecting collagen production and therefore has potential for improving outcomes for atrophic fracture nonunion.


Androgenic Atrophic Bone Healing Regeneration Steroid 



We thank Professor Dr Kurt Hankenson from University of Michigan, Professor Dr John Kastelic from University of Calgary and Professor Dr Concepta Margaret McManus Pimentel from Universidade Federal do Rio Grande do Sul for revising this manuscript. This study was partly funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) of the Brazilian Government doctorate scholarship program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Canadian Orthopaedic Trauma Society (2003) Nonunion following intramedullary nailing with and without reaming. Results of a multicenter randomized clinical trial. J Bone Jt Surg 83(11):2093–2096CrossRefGoogle Scholar
  2. 2.
    Mills LA, Hamish A, Simpson RW (2013) The relative incidence of fracture non-union in the Scottish population (5.17 million): a 5-year epidemiological study. BMJ 3(2):002276Google Scholar
  3. 3.
    Hak DJ, Fitzpatrick D, Bishop JA, Marsh JL, Tilp S, Schenettler R (2014) Delayed union and nonunions: epidemiology, clinical issue, and financial aspects. Injury 45(S2):3–7CrossRefGoogle Scholar
  4. 4.
    Rubin E, Farber JL (2002) Patologia. Editora Guanabara Koogan Ltda, Rio de JaneiroGoogle Scholar
  5. 5.
    Piermattei DL, Flo GL, DeCamp CE (2009) Brinker, Piermattei, Flo: Ortopedia e Tratamento de Fraturas de Pequenos Animais. Manole, BarueriGoogle Scholar
  6. 6.
    Roberto-Rodrigues M, Fernandes RMP, Senos R, Scoralick AC, Bastos AL, Santos TM (2015) Novel rat model of nonunion fracture with vascular deficit. Injury 46(4):649–654CrossRefGoogle Scholar
  7. 7.
    Heckman JD, Sarasohn-Kahn J (1997) The economics of treating tibia fractures: the cost of delayed unions. Bull Hosp Jt Dis 56(1):63–72Google Scholar
  8. 8.
    Kanakaris NK, Giannoudis PV (2007) The health economics of the treatment of long-bone non-unions. Injury 38(S2):77–86CrossRefGoogle Scholar
  9. 9.
    Kanakaris NK, Paliobeis C, Manidakis N, Giannoudis PV (2007) Biological enhancement of tibial diaphyseal aseptic non-unions: the efficacy of autologous bone grafting, BMPs and reaming by-products. Injury 38(s2):65–75CrossRefGoogle Scholar
  10. 10.
    Babhulkar SS, Pande K, Babhulkar S (2005) Nonunion of diaphysis of long bones. Clin Orthop Relat Res 431:50–56CrossRefGoogle Scholar
  11. 11.
    Kicman AT (2008) Pharmacology of anabolic steroids. Br J Pharmacol 154(3):502–521CrossRefGoogle Scholar
  12. 12.
    Geusens P (1995) Nandrolone decanoate: pharmacological properties and therapeutic use in osteoporosis. Clin Rheumatol 14(S3):32–39CrossRefGoogle Scholar
  13. 13.
    Nowakowski H (1962) Metabolic studies with anabolic steroids. Acta Endocrinol 39:37–53CrossRefGoogle Scholar
  14. 14.
    Need AG, Morris HA, Hartley TF, Horowitz M, Nordin BE (1987) Effects of nandrolone decanoate on forearm mineral density and calcium metabolism in osteoporotic postmenopausal women. Calcif Tissue Int 41(1):7–10CrossRefGoogle Scholar
  15. 15.
    Gennari C, AgnusDei D, Gonnelli S, Nardi P (1989) Effects of nandrolone decanoate therapy on bone mass and calcium metabolism in women with established post-menopausal osteoporosis: a double-blind placebo-controlled study. Maturitas 11(3):187–197CrossRefGoogle Scholar
  16. 16.
    Aerssens J, Audekerecke RV, Geusens P, Schot LP, Osman AA (1993) Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: influence of ovarectomy and nandrolone decanoate (anabolic steroid). Calcif Tissue Int 53(4):360–366CrossRefGoogle Scholar
  17. 17.
    Tidermark J, Ponzer S, Carlsson P (2004) Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fratures. Clin Nutr 23(4):587–596CrossRefGoogle Scholar
  18. 18.
    Ahmad F, Yunus SN, Asghar A, Faruqi NA (2013) Influence of anabolic steroid on tibial fracture healing in rabbits—a study on experimental model. J Clin Diagn Res 7(1):93–96Google Scholar
  19. 19.
    Hahn M, Vogel M, Pompesius-Kempa M, Delling G (1992) Trabecular bone pattern factor—a new parameter for simple quantification of bone microarchitecture. Bone 13(4):327–330CrossRefGoogle Scholar
  20. 20.
    Recker RR, Kimmel DB, Dempster D, Weinstein RS, Wronski TJ, Burr DB (2011) Issues in modern bone histomorphometry. Bone 49(5):955–964CrossRefGoogle Scholar
  21. 21.
    Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28(1):1–16CrossRefGoogle Scholar
  22. 22.
    Jerome CP, Power RA, Obasanjo IO, Register TC, Guidry M, Carlson CS, Weaver DS (1997) The androgenic anabolic steroid nandrolone decanoate prevents osteopenia and inhibits bone turnover in ovariectomized cynomolgus monkeys. Bone 20(4):355–364CrossRefGoogle Scholar
  23. 23.
    Hamdy RC, Moore SW, Whalen KE, Landy C (1998) Nandrolone decanoate for men with osteoporosis. Am J Ther 5(2):89–95CrossRefGoogle Scholar
  24. 24.
    Geusens P, Dequeker J (1986) Long-term effect of nandrolone decanoate, 1α hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rat in sympomatic osteoporotic: a double-blind controled study. Bone Miner 1(4):347–357Google Scholar
  25. 25.
    Passerti M, Pedrazzoni M, Pioli G, Butturini L, Ruys AH, Cortenraad MG (1993) Effects of nandrolone decanoate on bone mass in estabilished ostoporosis. Maturitas 17:211–219CrossRefGoogle Scholar
  26. 26.
    Erdtsieck RJ, Pols HAP, Van Kuijk C, Birkenhager-Frenkel DH, Zeelenberg J, Kooy PP (1994) Course of bone mass after hormonal replacement therapy with and without addition of nandrolone decanoate. J Bone Miner Res 9(2):277–283CrossRefGoogle Scholar
  27. 27.
    Orwoll ES (1996) Androgens as anabolic agents for bone. Trends Endocrinol Metab 7(3):77–84CrossRefGoogle Scholar
  28. 28.
    Pederson L, Kremer M, Judd J, Pascoe D, Spelsberg TC, Riggs BL (1999) Androgens regulate bone resorption activity of isolated osteoclasts in vitro. Proc Natl Acad Sci USA 96(2):505–510CrossRefGoogle Scholar
  29. 29.
    Michael H, Härkönen PL, Väänänen HK, Hentunen TA (2005) Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J Bone Miner Res 20(12):2224–2232CrossRefGoogle Scholar
  30. 30.
    Vanderschueren D, Bouillon R (1995) Androgens and bone. Calc Tissue Int 56(5):341–346CrossRefGoogle Scholar
  31. 31.
    Abu EO, Horner A, Kusec V, Triffit JT, Compston JE (1997) The localization of androgen receptors in human bone. J Clin Endocrinol Metab 82(10):3493–3497CrossRefGoogle Scholar
  32. 32.
    Sinnesael M, Claessens F, Boonen S, Vanderschueren D (2013) Novel insights in the regulation and mechanism of androgen action on bone. Curr Opin Endocrinol Diabetes Obes 20(3):240–244CrossRefGoogle Scholar

Copyright information

© Istituto Ortopedico Rizzoli 2019

Authors and Affiliations

  • R. Senos
    • 1
    • 2
    Email author
  • M. Roberto-Rodrigues
    • 3
  • R. M. P. Fernandes
    • 3
  • T. M. P. Santos
    • 4
  • L. P. Viana
    • 3
  • I. Lima
    • 4
  • M. A. Guzman-Silva
    • 5
  • M. S. Gomes
    • 6
  • R. E. G. Rici
    • 2
  • J. R. Kfoury Júnior
    • 2
  1. 1.Department of Biomedical SciencesTufts University – Cummings School of Veterinary MedicineNorth GraftonUSA
  2. 2.Department of Surgery, Faculty of Veterinary MedicineUniversidade de São PauloSão PauloBrazil
  3. 3.Department of MorphologyUniversidade Federal FluminenseNiteróiBrazil
  4. 4.Department of Nuclear EngineeringUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Department of PathologyUniversidade Federal FluminenseNiteróiBrazil
  6. 6.Department of Animal BiologyUniversidade Federal Rural do Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations