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The effects of visceral obesity and androgens on bone: trenbolone protects against loss of femoral bone mineral density and structural strength in viscerally obese and testosterone-deficient male rats

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Abstract

Summary

In males, visceral obesity and androgen deficiency often present together and result in harmful effects on bone. Our findings show that both factors are independently associated with adverse effects on femoral bone structure and strength, and trenbolone protects rats from diet-induced visceral obesity and consequently normalises femoral bone structural strength.

Introduction

In light of the rapidly increasing incidence of obesity and osteoporosis globally, and recent conjecture regarding the effects of visceral adiposity and testosterone deficiency on bone health, we investigated the effects of increased visceral adipose tissue (VAT) mass on femoral bone mineral density (BMD), structure and strength in normal weight rats with testosterone deficiency.

Methods

Male Wistar rats (n = 50) were fed either standard rat chow (CTRL, n = 10) or a high-fat/high-sugar diet (HF/HS, n = 40). Following 8 weeks of feeding, rats underwent sham surgery (CTRL, n = 10; HF/HS, n = 10) or orchiectomy (HF/HS + ORX, n = 30). Following a 4-week recovery period, mini-osmotic pumps containing either vehicle (CTRL, n = 10; HF/HS, n = 10; HF/HS + ORX, n = 10), 2.0 mg kg day−1, testosterone (HF/HS + ORX + TEST, n = 10) or 2.0 mg kg day−1 trenbolone (HF/HS + ORX + TREN, n = 10) were implanted for 8 weeks of treatment. Dual-energy X-ray absorptiometry and three-point bending tests were used to assess bone mass, structure and strength of femora.

Results

Diet-induced visceral obesity resulted in decreased bone mineral area (BMA) and content (BMC) and impaired femoral stiffness and strength. Orchiectomy further impaired BMA, BMC and BMD and reduced energy to failure in viscerally obese animals. Both TEST and TREN treatment restored BMA, BMC, BMD and energy to failure. Only TREN reduced visceral adiposity and improved femoral stiffness and strength.

Conclusions

Findings support a role for both visceral adiposity and testosterone deficiency as independent risk factors for femoral osteoporosis, adverse bone geometry and impaired bone strength in male rats. Trenbolone may be a more effective candidate for androgen replacement therapy than testosterone in viscerally obese testosterone-deficient males.

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References

  1. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M (2011) Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378(9793):815–825. doi:10.1016/S0140-6736(11)60814-3

    Article  PubMed  Google Scholar 

  2. Leslie WD, Morin SN (2014) Osteoporosis epidemiology 2013: implications for diagnosis, risk assessment, and treatment. Curr Opin Rheumatol 26(4):440–446. doi:10.1097/BOR.0000000000000064

    Article  CAS  PubMed  Google Scholar 

  3. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating G (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377(9765):557–567. doi:10.1016/S0140-6736(10)62037-5

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jin K, Simpkins JW, Ji X, Leis M, Stambler I (2015) The critical need to promote research of aging and aging-related diseases to improve health and longevity of the elderly population. Aging dis 6(1):1–5. doi:10.14336/AD.2014.1210

    Article  PubMed  Google Scholar 

  5. Reid IR, Plank LD, Evans MC (1992) Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab 75(3):779–782. doi:10.1210/jcem.75.3.1517366

    CAS  PubMed  Google Scholar 

  6. Khosla S, Melton LJ 3rd, Atkinson EJ, O’Fallon WM (2001) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 86(8):3555–3561. doi:10.1210/jcem.86.8.7736

    Article  CAS  PubMed  Google Scholar 

  7. Despres JP, Lemieux I, Prud’homme D (2001) Treatment of obesity: need to focus on high risk abdominally obese patients. BMJ 322(7288):716–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. du Toit EF, Nabben M, Lochner A (2005) A potential role for angiotensin II in obesity induced cardiac hypertrophy and ischaemic/reperfusion injury. Basic Res Cardiol 100(4):346–354. doi:10.1007/s00395-005-0528-5

    Article  PubMed  Google Scholar 

  9. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S (2007) Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56(4):1010–1013. doi:10.2337/db06-1656

    Article  CAS  PubMed  Google Scholar 

  10. Schett G (2011) Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest 41(12):1361–1366. doi:10.1111/j.1365-2362.2011.02545.x

    Article  CAS  PubMed  Google Scholar 

  11. Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD (2009) Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94(9):3387–3393. doi:10.1210/jc.2008-2422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW (2007) Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 92(5):1640–1646. doi:10.1210/jc.2006-0572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bleicher K, Cumming RG, Naganathan V, Travison TG, Sambrook PN, Blyth FM, Handelsman DJ, Le Couteur DG, Waite LM, Creasey HM, Seibel MJ (2011) The role of fat and lean mass in bone loss in older men: findings from the CHAMP study. Bone 49(6):1299–1305. doi:10.1016/j.bone.2011.08.026

    Article  PubMed  Google Scholar 

  14. Choi HS, Kim KJ, Kim KM, Hur NW, Rhee Y, Han DS, Lee EJ, Lim SK (2010) Relationship between visceral adiposity and bone mineral density in Korean adults. Calcif Tissue Int 87(3):218–225. doi:10.1007/s00223-010-9398-4

    Article  CAS  PubMed  Google Scholar 

  15. Yamaguchi T, Kanazawa I, Yamamoto M, Kurioka S, Yamauchi M, Yano S, Sugimoto T (2009) Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes. Bone 45(2):174–179. doi:10.1016/j.bone.2009.05.003

    Article  CAS  PubMed  Google Scholar 

  16. Kim HI, Kim JT, Yu SH, Kwak SH, Jang HC, Park KS, Kim SY, Lee HK, Cho YM (2011) Gender differences in diagnostic values of visceral fat area and waist circumference for predicting metabolic syndrome in Koreans. J Korean Med Sci 26(7):906–913. doi:10.3346/jkms.2011.26.7.906

    Article  PubMed  PubMed Central  Google Scholar 

  17. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM (1995) Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest 96(1):88–98. doi:10.1172/JCI118083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ornstrup MJ, Kjaer TN, Harslof T, Stodkilde-Jorgensen H, Hougaard DM, Cohen A, Pedersen SB, Langdahl BL (2015) Adipose tissue, estradiol levels, and bone health in obese men with metabolic syndrome. Eur J Endocrinol 172(2):205–216. doi:10.1530/EJE-14-0792

    Article  PubMed  Google Scholar 

  19. Schneider HJ, Sievers C, Klotsche J, Bohler S, Pittrow D, Lehnert H, Wittchen HU, Stalla GK (2009) Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study. Clin Endocrinol (Oxf) 70(3):446–454. doi:10.1111/j.1365-2265.2008.03370.x

    Article  Google Scholar 

  20. Tajar A, Huhtaniemi IT, O’Neill TW, Finn JD, Pye SR, Lee DM, Bartfai G, Boonen S, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Wu FC, Group E (2012) Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab 97(5):1508–1516. doi:10.1210/jc.2011-2513

    Article  CAS  PubMed  Google Scholar 

  21. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR, Baltimore Longitudinal Study of A (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore longitudinal study of aging. J Clin Endocrinol Metab 86(2):724–731. doi:10.1210/jcem.86.2.7219

    Article  CAS  PubMed  Google Scholar 

  22. Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, O’Donnell AB, McKinlay JB (2008) The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriatr Soc 56(5):831–839. doi:10.1111/j.1532-5415.2008.01679.x

    Article  PubMed  Google Scholar 

  23. Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C (2006) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J bone miner res: official j Am Soc Bone Miner Res 21(4):529–535. doi:10.1359/jbmr.060110

    Article  Google Scholar 

  24. Stepan JJ, Lachman M, Zverina J, Pacovsky V, Baylink DJ (1989) Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 69(3):523–527. doi:10.1210/jcem-69-3-523

    Article  CAS  PubMed  Google Scholar 

  25. Saboor Aftab SA, Kumar S, Barber TM (2013) The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol (Oxf) 78(3):330–337. doi:10.1111/cen.12092

    Article  CAS  Google Scholar 

  26. Donner DG, Beck BR, Bulmer AC, Lam AK, Du Toit EF (2015) Improvements in body composition, cardiometabolic risk factors and insulin sensitivity with trenbolone in normogonadic rats. Steroids 94:60–69. doi:10.1016/j.steroids.2014.12.017

    Article  CAS  PubMed  Google Scholar 

  27. Donner D, Headrick JP, Peart JN, du Toit EF (2013) Obesity improves myocardial ischaemic tolerance and RISK signalling in insulin-insensitive rats. Dis Model Mech 6(2):457–466. doi:10.1242/dmm.010959

    Article  CAS  PubMed  Google Scholar 

  28. Turner CH, Burr DB (1993) Basic biomechanical measurements of bone: a tutorial. Bone 14(4):595–608

    Article  CAS  PubMed  Google Scholar 

  29. Schriefer JL, Robling AG, Warden SJ, Fournier AJ, Mason JJ, Turner CH (2005) A comparison of mechanical properties derived from multiple skeletal sites in mice. J Biomech 38(3):467–475. doi:10.1016/j.jbiomech.2004.04.020

    Article  PubMed  Google Scholar 

  30. Taes YE, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Zmierczak H, Goemaere S, Kaufman JM (2009) Fat mass is negatively associated with cortical bone size in young healthy male siblings. J Clin Endocrinol Metab 94(7):2325–2331. doi:10.1210/jc.2008-2501

    Article  CAS  PubMed  Google Scholar 

  31. Zhang P, Peterson M, Su GL, Wang SC (2015) Visceral adiposity is negatively associated with bone density and muscle attenuation. Am J Clin Nutr 101(2):337–343. doi:10.3945/ajcn.113.081778

    Article  CAS  PubMed  Google Scholar 

  32. Borst SE, Conover CF (2006) Orchiectomized Fischer 344 male rat models body composition in hypogonadal state. Life Sci 79(4):411–415. doi:10.1016/j.lfs.2006.01.035

    Article  CAS  PubMed  Google Scholar 

  33. Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, Orwoll ES (2006) Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab 91(10):3908–3915. doi:10.1210/jc.2006-0173

    Article  CAS  PubMed  Google Scholar 

  34. Knapp PE, Storer TW, Herbst KL, Singh AB, Dzekov C, Dzekov J, LaValley M, Zhang A, Ulloor J, Bhasin S (2008) Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am J Physiol Endocrinol Metab 294(6):E1135–1143. doi:10.1152/ajpendo.90213.2008

    Article  CAS  PubMed  Google Scholar 

  35. Yarrow JF, Conover CF, McCoy SC, Lipinska JA, Santillana CA, Hance JM, Cannady DF, VanPelt TD, Sanchez J, Conrad BP, Pingel JE, Wronski TJ, Borst SE (2011) 17beta-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate. Am J Physiol Endocrinol Metab 300(4):E650–660. doi:10.1152/ajpendo.00440.2010

    Article  CAS  PubMed  Google Scholar 

  36. Bjorntorp P (1997) Neuroendocrine factors in obesity. J Endocrinol 155(2):193–195

    Article  CAS  PubMed  Google Scholar 

  37. Freedland ES (2004) Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutrition metabol 1(1):12. doi:10.1186/1743-7075-1-12

    Article  Google Scholar 

  38. Haendler B, Cleve A (2012) Recent developments in antiandrogens and selective androgen receptor modulators. Mol Cell Endocrinol 352(1–2):79–91. doi:10.1016/j.mce.2011.06.002

    Article  CAS  PubMed  Google Scholar 

  39. Cleland WH, Mendelson CR, Simpson ER (1985) Effects of aging and obesity on aromatase activity of human adipose cells. J Clin Endocrinol Metab 60(1):174–177

    Article  CAS  PubMed  Google Scholar 

  40. Pottier J, Cousty C, Heitzman RJ, Reynolds IP (1981) Differences in the biotransformation of a 17 beta-hydroxylated steroid, trenbolone acetate, in rat and cow. Xenobiotica; fate foreign compounds biol syst 11(7):489–500

    Article  CAS  Google Scholar 

  41. Yarrow JF, McCoy SC, Borst SE (2010) Tissue selectivity and potential clinical applications of trenbolone (17beta-hydroxyestra-4,9,11-trien-3-one): a potent anabolic steroid with reduced androgenic and estrogenic activity. Steroids 75(6):377–389. doi:10.1016/j.steroids.2010.01.019

    Article  CAS  PubMed  Google Scholar 

  42. Abdelhamed A, Hisasue S, Shirai M, Matsushita K, Wakumoto Y, Tsujimura A, Tsukamoto T, Horie S (2015) Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model. Res Rep Urol 7:35–40. doi:10.2147/RRU.S72253

    CAS  PubMed  PubMed Central  Google Scholar 

  43. McCoy SC, Yarrow JF, Conover CF, Borsa PA, Tillman MD, Conrad BP, Pingel JE, Wronski TJ, Johnson SE, Kristinsson HG, Ye F, Borst SE (2012) 17beta-Hydroxyestra-4,9,11-trien-3-one (trenbolone) preserves bone mineral density in skeletally mature orchiectomized rats without prostate enlargement. Bone 51(4):667–673. doi:10.1016/j.bone.2012.07.008

    Article  CAS  PubMed  Google Scholar 

  44. Crossno JT Jr, Majka SM, Grazia T, Gill RG, Klemm DJ (2006) Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 116(12):3220–3228. doi:10.1172/JCI28510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, Rubin CT (2009) Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J bone miner res: official j Am Soc Bone Miner Res 24(1):50–61. doi:10.1359/jbmr.080817

    Article  CAS  Google Scholar 

  46. Rubin CT, Capilla E, Luu YK, Busa B, Crawford H, Nolan DJ, Mittal V, Rosen CJ, Pessin JE, Judex S (2007) Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc Natl Acad Sci U S A 104(45):17879–17884. doi:10.1073/pnas.0708467104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ray R, Novotny NM, Crisostomo PR, Lahm T, Abarbanell A, Meldrum DR (2008) Sex steroids and stem cell function. Mol Med 14(7–8):493–501. doi:10.2119/2008-00004.Ray

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by funds from the Menzies Health Institute Queensland, Griffith University, Australia. The authors would like to thank Ms. Rossana Nogueira in obtaining and processing high-resolution DXA images for use in this study.

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    Authors and Affiliations

    1. Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia

      D. G. Donner, G. E. Elliott & E. F. Du Toit

    2. School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia

      M. R. Forwood

    3. School of Allied Health Sciences, Griffith University, Gold Coast, Queensland, Australia

      B. R. Beck

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    1. D. G. Donner
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    D. G. Donner and G. E. Elliott contributed equally to this work.

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    Donner, D.G., Elliott, G.E., Beck, B.R. et al. The effects of visceral obesity and androgens on bone: trenbolone protects against loss of femoral bone mineral density and structural strength in viscerally obese and testosterone-deficient male rats. Osteoporos Int 27, 1073–1082 (2016). https://doi.org/10.1007/s00198-015-3345-1

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