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Bone mineral density and its determinants in men with opioid dependence


Data on the influence of opioid substitution therapy (OST) on skeletal health in men is limited. This cross-sectional study aimed to determine the prevalence of low bone mass in male drug users and to evaluate the relationship between endogenous testosterone and bone mass. We recruited 144 men on long-term opioid maintenance therapy followed in the Center of Addiction Medicine in Basel, Switzerland. Data on medical and drug history, fracture risk and history of falls were collected. Bone mineral density (BMD) was evaluated by densitometry and serum was collected for measurements of gonadal hormones and bone markers. 35 healthy age- and BMI-matched men served as the control group. The study participants received OST with methadone (69 %), morphine (25 %) or buprenorphine (6 %). Overall, 74.3 % of men had low bone mass, with comparable bone mass irrespective of OST type. In older men (≥40 years, n = 106), 29.2 % of individuals were osteoporotic (mean T-score −3.0 ± 0.4 SD) and 48.1 % were diagnosed with osteopenia (mean T-score −1.7 ± 0.4 SD). In younger men (n = 38), 65.8 % of men had low bone mass. In all age groups, BMD was significantly lower than in age-and BMI-matched controls. In multivariate analyses, serum free testosterone (fT) was significantly associated with low BMD at the lumbar spine (p = 0.02), but not at the hip. When analysed by quartiles of fT, lumbar spine BMD decreased progressively with decreasing testosterone levels. We conclude that low bone mass is highly prevalent in middle-aged men on long-term opioid dependency, a finding which may partly be determined by partial androgen deficiency.

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  1. 1.

    Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Vestergaard P, Rejnmark L, Mosekilde L (2005) Osteoporosis is markedly underdiagnosed: a nationwide study from Denmark. Osteoporos Int 16:134–141

    Article  PubMed  Google Scholar 

  3. 3.

    Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY (2013) Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Kim TW, Alford DP, Malabanan A, Holick MF, Samet JH (2006) Low bone density in patients receiving methadone maintenance treatment. Drug Alcohol Depend 85:258–262

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Grey A, Rix-Trott K, Horne A, Gamble G, Bolland M, Reid IR (2011) Decreased bone density in men on methadone maintenance therapy. Addiction 106:349–354

    Article  PubMed  Google Scholar 

  6. 6.

    Dursteler-MacFarland KM, Kowalewski R, Bloch N, Wiesbeck GA, Kraenzlin ME, Stohler R (2011) Patients on injectable diacetylmorphine maintenance have low bone mass. Drug Alcohol Rev 30:577–582

    Article  PubMed  Google Scholar 

  7. 7.

    Jutberger H, Lorentzon M, Barrett-Connor E, Johansson H, Kanis JA, Ljunggren O, Karlsson MK, Rosengren BE, Redlund-Johnell I, Orwoll E, Ohlsson C, Mellstrom D (2010) Smoking predicts incident fractures in elderly men: Mr OS Sweden. J Bone Miner Res 25:1010–1016

    PubMed  Google Scholar 

  8. 8.

    Kim MJ, Shim MS, Kim MK, Lee Y, Shin YG, Chung CH, Kwon SO (2003) Effect of chronic alcohol ingestion on bone mineral density in males without liver cirrhosis. Korean J Intern Med 18:174–180

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Berg KM, Kunins HV, Jackson JL, Nahvi S, Chaudhry A, Harris KA Jr, Malik R, Arnsten JH (2008) Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 121:406–418

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Malik P, Gasser RW, Kemmler G, Moncayo R, Finkenstedt G, Kurz M, Fleischhacker WW (2009) Low bone mineral density and impaired bone metabolism in young alcoholic patients without liver cirrhosis: a cross-sectional study. Alcohol Clin Exp Res 33:375–381

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Nakchbandi IA (2014) Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications. World J Gastroenterol 20:9427–9438

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Trautwein C, Possienke M, Schlitt HJ, Boker KH, Horn R, Raab R, Manns MP, Brabant G (2000) Bone density and metabolism in patients with viral hepatitis and cholestatic liver diseases before and after liver transplantation. Am J Gastroenterol 95:2343–2351

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Giouleme OI, Vyzantiadis TA, Nikolaidis NL, Vasiliadis TG, Papageorgiou AA, Eugenidis NP, Harsoulis FI (2006) Pathogenesis of osteoporosis in liver cirrhosis. Hepatogastroenterology 53:938–943

    PubMed  Google Scholar 

  14. 14.

    Li M, Xu Y, Xu M, Ma L, Wang T, Liu Y, Dai M, Chen Y, Lu J, Liu J, Bi Y, Ning G (2012) Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab 97:2033–2038

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Asomaning K, Bertone-Johnson ER, Nasca PC, Hooven F, Pekow PS (2006) The association between body mass index and osteoporosis in patients referred for a bone mineral density examination. J Womens Health (Larchmt) 15:1028–1034

    Article  Google Scholar 

  16. 16.

    Forrester JE (2006) Nutritional alterations in drug abusers with and without HIV. Am J Infect Dis 2:173–179

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmuller D (2005) Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab 90:203–206

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Bawor M, Dennis BB, Samaan MC, Plater C, Worster A, Varenbut M, Daiter J, Marsh DC, Desai D, Steiner M, Anglin R, Coote M, Pare G, Thabane L, Samaan Z (2014) Methadone induces testosterone suppression in patients with opioid addiction. Sci Rep 4:6189

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Hallinan R, Byrne A, Agho K, McMahon CG, Tynan P, Attia J (2009) Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Int J Androl 32:131–139

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, Kaur G, Bruera E (2004) Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer 100:851–858

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Daniell HW (2002) Hypogonadism in men consuming sustained-action oral opioids. J Pain 3:377–384

    Article  PubMed  Google Scholar 

  22. 22.

    Bawor M, Bami H, Dennis BB, Plater C, Worster A, Varenbut M, Daiter J, Marsh DC, Steiner M, Anglin R, Coote M, Pare G, Thabane L, Samaan Z (2015) Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug Alcohol Depend 149:1–9

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Katz N, Mazer NA (2009) The impact of opioids on the endocrine system. Clin J Pain 25:170–175

    Article  PubMed  Google Scholar 

  24. 24.

    Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D (2013) Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497:211–216

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Meier C, Seibel MJ, Handelsman DJ (2009) Testicular dysfunction and bone. In: Orwoll E, Bilezikian J, Vanderschueren D (eds) Osteoporosis in men, 2nd edn. Academic Press, San Diego, pp 423–434

    Google Scholar 

  26. 26.

    Gomez B Jr, Ardakani S, Ju J, Jenkins D, Cerelli MJ, Daniloff GY, Kung VT (1995) Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin Chem 41:1560–1566

    CAS  PubMed  Google Scholar 

  27. 27.

    Garnero P, Borel O, Delmas PD (2001) Evaluation of a fully automated serum assay for C-terminal cross- linking telopeptide of type I collagen in osteoporosis. Clin Chem 47:694–702

    CAS  PubMed  Google Scholar 

  28. 28.

    Schmidt-Gayk H, Spanuth E, Kotting J, Bartl R, Felsenberg D, Pfeilschifter J, Raue F, Roth HJ (2004) Performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone (BIOROSE Multicenter Study). Clin Chem Lab Med 42:90–95

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Keel C, Kraenzlin ME, Kraenzlin CA, Muller B, Meier C (2010) Impact of bisphosphonate wash-out prior to teriparatide therapy in clinical practice. J Bone Miner Metab 28:68–76

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Gluer CC, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK (1995) Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int 5:262–270

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Vestergaard P, Rejnmark L, Mosekilde L (2006) Fracture risk associated with the use of morphine and opiates. J Intern Med 260:76–87

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Takkouche B, Montes-Martinez A, Gill SS, Etminan M (2007) Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 30:171–184

    Article  PubMed  Google Scholar 

  34. 34.

    Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Smoking and fracture risk: a meta-analysis. Osteoporos Int 16:155–162

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Snyder PJ (2001) Effects of age on testicular function and consequences of testosterone treatment. J Clin Endocrinol Metab 86:2369–2372

    CAS  PubMed  Google Scholar 

  36. 36.

    Pignata S, Daniele B, Galati MG, Esposito G, Vallone P, Fiore F, Ricchi P, Pergola M (1997) Oestradiol and testosterone blood levels in patients with viral cirrhosis and hepatocellular carcinoma. Eur J Gastroenterol Hepatol 9:283–286

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Nguyen HV, Mollison LC, Taylor TW, Chubb SA, Yeap BB (2006) Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy. Intern Med J 36:362–366

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    De Besi L, Zucchetta P, Zotti S, Mastrogiacomo I (1989) Sex hormones and sex hormone binding globulin in males with compensated and decompensated cirrhosis of the liver. Acta Endocrinol (Copenh) 120:271–276

    Google Scholar 

  39. 39.

    Guechot J, Chazouilleres O, Loria A, Hannoun L, Balladur P, Parc R, Giboudeau J, Poupon R (1994) Effect of liver transplantation on sex-hormone disorders in male patients with alcohol-induced or post-viral hepatitis advanced liver disease. J Hepatol 20:426–430

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Iturriaga H, Lioi X, Valladares L (1999) Sex hormone-binding globulin in non-cirrhotic alcoholic patients during early withdrawal and after longer abstinence. Alcohol Alcohol 34:903–909

    CAS  Article  PubMed  Google Scholar 

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We would like to thank all patients for their willingness to participate in the study. We thank the staff involved in the Basel Center for Addiction Medicine and the Division of Endocrinology, University Hospital Basel for their patience in dealing with our study participants, with special thanks to Mrs. Kradolfer. The study was supported by unrestricted educational grants from “Freiwillige Akademische Gesellschaft Basel”, “Verein für Drogenarbeit Basel”, and Roche Pharma (Switzerland).

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Correspondence to Christian Meier.

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Gotthardt, F., Huber, C., Thierfelder, C. et al. Bone mineral density and its determinants in men with opioid dependence. J Bone Miner Metab 35, 99–107 (2017).

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  • Osteoporosis
  • Opioid dependence
  • Testosterone
  • Bone mineral density