Adverse Effects of Drugs on Bone and Calcium Metabolism/Physiology

Original Paper


Drugs may affect bone turnover and density in many ways. However, the disease for which the drugs are administered may also contribute to bone loss. Infection with human immunodeficiency virus leads to a loss of bone mineral, while treatment with highly active antiretroviral therapy does not seem to contribute to further bone loss. Type 1 diabetes is associated with a decrease in bone mineral, while type 2 diabetes is associated with an increase. The new class of thiazolidinediones (glitazones) has been associated with an increased loss of bone mineral. In breast cancer treatment, tamoxifen is associated with an increased bone mineral, while the newer class of aromatase inhibitors through a decrease in serum oestradiol are associated with an increased loss of bone mineral. Strong analgesics (opioids) may decrease bone mineral density through inhibition of gonadotrophins while weak analgesics such as the non-steroidal anti-inflammatory drugs may increase bone mineral through an effect on the prostaglandin system. However, possibly through an increased risk of falls, the weak analgesics are associated with an increased risk of fractures. Proton pump inhibitors may lead to a decreased calcium absorption and thus a decreased bone mineral and an increased risk of fractures.


Bone mineral Drugs Highly active antiretroviral therapy Diabetes Thiazolidinediones Glitazones 


  1. 1.
    Arnsten JH, Freeman R, Howard AA, et al. HIV infection and bone mineral density in middle-aged women. Clin Infect Dis 2006;42:1014–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Loiseau-Peres S, Delaunay C, Poupon S, et al. Osteopenia in patients infected by the human immunodeficiency virus. A case control study. Joint Bone Spine 2002;69:482–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Bonnet E, Delpierre C, Sommet A, et al. Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy. J Clin Densitom 2005;8:287–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Brown TT, Ruppe MD, Kassner R, et al. Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia. J Clin Endocrinol Metab 2004;89:1200–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Dolan SE, Kanter JR, Grinspoon S. Longitudinal analysis of bone density in human immunodeficiency virus-infected women. J Clin Endocrinol Metab 91: 2006;2938–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Ellis KJ, Shypailo RJ, Hardin DS, et al. Z score prediction model for assessment of bone mineral content in pediatric diseases. J Bone Miner Res 2001;16:1658–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Fairfield WP, Finkelstein JS, Klibanski A, et al. Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome. J Clin Endocrinol Metab 2001;86:2020–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Jacobson DL, Spiegelman D, Duggan C, et al. Predictors of bone mineral density in human immunodeficiency virus-1 infected children. J Pediatr Gastroenterol Nutr 2005;41:339–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Ozcakar L, Guven GS, Unal S, et al. Osteoporosis In Turkish HIV/AIDS patients: comparative analysis by dual energy X-ray absorptiometry and digital X-ray radiogrammetry. Osteoporos Int 2005;16:1363–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Pitukcheewanont P, Safani D, Church J, et al. Bone measures in HIV-1 infected children and adolescents: disparity between quantitative computed tomography and dual-energy X-ray absorptiometry measurements. Osteoporos Int 2005;16:1393–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Rosenthall L, Falutz J. Bone mineral and soft-tissue changes in AIDS-associated lipoatrophy. J Bone Miner Metab 2005;23:53–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Teichmann J, Stephan E, Discher T, et al. Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection. Metabolism 2000;49:1134–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Paton NI, Macallan DC, Griffin GE, et al. Bone mineral density in patients with human immunodeficiency virus infection. Calcif Tissue Int 1997;61:30–2.PubMedCrossRefGoogle Scholar
  14. 14.
    Serrano S, Marinoso ML, Soriano JC, et al. Bone remodelling in human immunodeficiency virus-1-infected patients. A histomorphometric study. Bone 1995;16:185–91.PubMedCrossRefGoogle Scholar
  15. 15.
    Arnsten JH, Freeman R, Howard AA, et al. Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS 2007;21:617–23.PubMedCrossRefGoogle Scholar
  16. 16.
    Bongiovanni M, Tincati C. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management. Curr Mol Med 2006;6:395–400.PubMedCrossRefGoogle Scholar
  17. 17.
    Brown TT, McComsey GA. Osteopenia and osteoporosis in patients with HIV: a review of current concepts. Curr Infect Dis Rep 2006;8:162–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Glesby MJ. Bone disorders in human immunodeficiency virus infection. Clin Infect Dis 2003;37(Suppl 2):S91–S95.PubMedCrossRefGoogle Scholar
  19. 19.
    Panayotakopoulos GD, Day S, Peters BS, et al. Severe osteoporosis and multiple fractures in an AIDS patient treated with short-term steroids for lymphoma: a need for guidelines. Int J STD AIDS 2006;17:567–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Dobs A. Role of testosterone in maintaining lean body mass and bone density in HIV-infected patients. Int J Impot Res 2003;15(Suppl 4):S21–S25.PubMedCrossRefGoogle Scholar
  21. 21.
    Cooper OB, Brown TT, Dobs AS. Opiate drug use: a potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease. Clin Infect Dis 2003;37(Suppl 2):S132–S136.PubMedCrossRefGoogle Scholar
  22. 22.
    Giri M, Kaufman JM. Opioidergic modulation of in vitro pulsatile gonadotropin-releasing hormone release from the isolated medial basal hypothalamus of the male guinea pig. Endocrinology 1994;135:2137–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Zamboni G, Antoniazzi F, Bertoldo F, et al. Altered bone metabolism in children infected with human immunodeficiency virus. Acta Paediatr 2003;92:12–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Tan BM, Nelson RP Jr., James-Yarish M, et al. Bone metabolism in children with human immunodeficiency virus infection receiving highly active anti-retroviral therapy including a protease inhibitor. J Pediatr 2001;139:447–51.PubMedCrossRefGoogle Scholar
  25. 25.
    Pan G, Yang Z, Ballinger SW, et al. Pathogenesis of osteopenia/osteoporosis induced by highly active anti-retroviral therapy for AIDS. Ann N Y Acad Sci 2006;1068:297–308.PubMedCrossRefGoogle Scholar
  26. 26.
    Garcia Aparicio AM, Munoz FS, Gonzalez J, et al. Abnormalities in the bone mineral metabolism in HIV-infected patients. Clin Rheumatol 2006;25:537–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Cozzolino M, Vidal M, Arcidiacono MV, et al. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS 2003;17:513–20.PubMedCrossRefGoogle Scholar
  28. 28.
    de la Prada FJ, Prados AM, Tugores A, et al. [Acute renal failure and proximal renal tubular dysfunction in a patient with acquired immunodeficiency syndrome treated with tenofovir]. Nefrologia 2006;26:626–30.Google Scholar
  29. 29.
    Earle KE, Seneviratne T, Shaker J, et al. Fanconi’s syndrome in HIV+ adults: report of three cases and literature review. J Bone Miner Res 2004;19:714–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Jain RG, Lenhard JM. Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J Biol Chem 2002;277:19247–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Bolland MJ, Grey AB, Horne AM, et al. Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy. Clin Endocrinol (Oxf) 2006;65:191–7.CrossRefGoogle Scholar
  32. 32.
    Bolland MJ, Grey AB, Horne AM, et al. Bone mineral density remains stable in HAART-treated HIV-infected men over 2 years. Clin Endocrinol (Oxf) 2007;67:270–5.CrossRefGoogle Scholar
  33. 33.
    Cassetti I, Madruga JV, Suleiman JM, et al. The Safety and Efficacy of Tenofovir DF in Combination with Lamivudine and Efavirenz Through 6 Years in Antiretroviral-Naive HIV-1-Infected Patients. HIV Clin Trials 2007;8:164–72.PubMedCrossRefGoogle Scholar
  34. 34.
    Cirelli A, Cirelli G, Balsamo G, et al. Body habitus changes, metabolic abnormalities, osteopenia and cardiovascular risk in patients treated for human immunodeficiency virus infection. Ann Ital Med Int 2003;18:238–45.PubMedGoogle Scholar
  35. 35.
    Dube MP, Qian D, Edmondson-Melancon H, et al. Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavir-based antiretroviral therapy. Clin Infect Dis 2002;35:475–81.PubMedCrossRefGoogle Scholar
  36. 36.
    Fausto A, Bongiovanni M, Cicconi P, et al. Potential predictive factors of osteoporosis in HIV-positive subjects. Bone 2006;38:893–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Mondy K, Yarasheski K, Powderly WG, et al. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis 2003;36:482–90.PubMedCrossRefGoogle Scholar
  38. 38.
    Mora S, Zamproni I, Beccio S, et al. Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children. J Clin Endocrinol Metab 2004;89:24–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Tebas P, Yarasheski K, Henry K, et al. Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection. AIDS Res Hum Retrovir 2004;20:589–94.PubMedCrossRefGoogle Scholar
  40. 40.
    Guaraldi G, Ventura P, Albuzza M, et al. Pathological fractures in AIDS patients with osteopenia and osteoporosis induced by antiretroviral therapy. AIDS 2001;15:137–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004;292:191–201.PubMedCrossRefGoogle Scholar
  42. 42.
    Bolland MJ, Grey AB, Horne AM, et al. Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab 2007;92:1283–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Negredo E, Martinez-Lopez E, Paredes R, et al. Reversal of HIV-1-associated osteoporosis with once-weekly alendronate. AIDS 2005;19:343–5.PubMedGoogle Scholar
  44. 44.
    Vestergaard P. Osteoporosis and fracture risk in patients with diabetes. SIIC 2006;11:1.Google Scholar
  45. 45.
    Raskin P, Stevenson MRM, Barilla DE, et al. The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol 1978;9:329–35.CrossRefGoogle Scholar
  46. 46.
    McNair P, Madsbad S, Christensen MS, et al. Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol 1979;90:463–72.PubMedGoogle Scholar
  47. 47.
    Bouillon R. Diabetic bone disease [editorial]. Calcif Tissue Int 1991;49:155–60.PubMedCrossRefGoogle Scholar
  48. 48.
    Hein G, Weiss C, Lehmann G, et al. Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings. Ann Rheum Dis 2006;65:101–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Saito M, Fujii K, Soshi S, et al. Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture. Osteoporos Int 2006;17(7):986–95.PubMedCrossRefGoogle Scholar
  50. 50.
    Yamagishi S, Nakamura K, Inoue H. Possible participation of advanced glycation end products in the pathogenesis of osteoporosis in diabetic patients. Med Hypotheses 2005;65:1013–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes-a meta-analysis. Osteoporos Int 2007;18:427–44.PubMedCrossRefGoogle Scholar
  52. 52.
    Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 2005;48:1292–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–43.PubMedCrossRefGoogle Scholar
  54. 54.
    Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Tornvig L, Mosekilde LI, Justesen J, et al. Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice. Calcif Tissue Int 2001;69:46–50.PubMedCrossRefGoogle Scholar
  56. 56.
    Ali AA, Weinstein RS, Stewart SA, et al. Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 2005;146:1226–35.PubMedCrossRefGoogle Scholar
  57. 57.
    Soroceanu MA, Miao D, Bai XY, et al. Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. J Endocrinol 2004;183:203–16.PubMedCrossRefGoogle Scholar
  58. 58.
    Schwartz AV, Sellmeyer DE, Vittinghoff E, et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006;91:3349–54.PubMedCrossRefGoogle Scholar
  59. 59.
    Short R. Fracture risk is a class effect of glitazones. BMJ 2007;334:551.PubMedCrossRefGoogle Scholar
  60. 60.
    Eastell R, Hannon RA, Cuzick J, et al. Effect of an aromatase inhibitor on bmd and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res 2006;21:1215–23.PubMedCrossRefGoogle Scholar
  61. 61.
    Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002;359:2131–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Perez EA, Josse RG, Pritchard KI, et al. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol 2006;24:3629–35.PubMedCrossRefGoogle Scholar
  63. 63.
    Coleman RE, Banks LM, Girgis SI, et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 2007;8:119–27.PubMedCrossRefGoogle Scholar
  64. 64.
    Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med 2001;344:1997–2008.PubMedCrossRefGoogle Scholar
  65. 65.
    Bruning PF, Pit MJ, Jong-Bakker M, et al. Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer 1990;61:308–10.PubMedGoogle Scholar
  66. 66.
    Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254–9.PubMedGoogle Scholar
  67. 67.
    Fogelman I, Blake GM, Blamey R, et al. Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporos Int 2003;14:1001–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Vehmanen L, Saarto T, Elomaa I, et al. Long-term impact of chemotherapy-induced ovarian failure on bone mineral density (BMD) in premenopausal breast cancer patients. The effect of adjuvant clodronate treatment. Eur J Cancer 2001;37:2373–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Saarto T, Blomqvist C, Valimaki M, et al. Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 1997;15:1341–7.PubMedGoogle Scholar
  70. 70.
    Headley JA, Theriault RL, LeBlanc AD, et al. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy. Cancer Invest 1998;16:6–11.PubMedCrossRefGoogle Scholar
  71. 71.
    Shapiro CL, Phillips G, Van Poznak CH, et al. Baseline bone mineral density of the total lumbar spine may predict for chemotherapy-induced ovarian failure. Breast Cancer Res Treat 2005;90:41–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Alexeeva L, Burkhardt P, Christiansen C, Cooper C, Delmas P, Johnell O, et al. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO Study Group. Geneva: WHO Technical Report Series 843, 1994. pp. 1–129.Google Scholar
  73. 73.
    Cegiela U, Piatek A, Janiec W, et al. [Effect of cyclophosphamide on bone remodeling in rats]. Przegl Lek 2003;60:329–33.PubMedGoogle Scholar
  74. 74.
    Wie H, Beck EI. Synthesis and solubility of collagen in rats during recovery after high-dose cyclophosphamide administration. Acta Pharmacol Toxicol (Copenh) 1981;48:294–9.Google Scholar
  75. 75.
    Glorieux F, Bishop NJ, Plotkin H, et al. Cyclic asministration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998;339:947–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Langendorff HU, Sauer HD, Schottle H, et al. [The influence of cyclophosphamide upon the healing of fractures in the rabbit (author’s transl)]. Unfallchirurgie 1981;7:231–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Buckley LM, Leib ES, Cartularo KS, et al. Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 1997;24:1489–94.PubMedGoogle Scholar
  78. 78.
    Carbone LD, Kaeley G, McKown KM, et al. Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis. Calcif Tissue Int 1999;64:100–1.PubMedCrossRefGoogle Scholar
  79. 79.
    Cranney AB, McKendry RJ, Wells GA, et al. The effect of low dose methotrexate on bone density. J Rheumatol 2001;28:2395–9.PubMedGoogle Scholar
  80. 80.
    di Munno O, Mazzantini M, Sinigaglia L, et al. Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study. J Rheumatol 2004;31:1305–9.PubMedGoogle Scholar
  81. 81.
    Mazzantini M, di Munno O, Incerti-Vecchi L, et al. Vertebral bone mineral density changes in female rheumatoid arthritis patients treated with low-dose methotrexate. Clin Exp Rheumatol 2000;18:327–31.PubMedGoogle Scholar
  82. 82.
    Tascioglu F, Oner C, Armagan O. The effect of low-dose methotrexate on bone mineral density in patients with early rheumatoid arthritis. Rheumatol Int 2003;23:231–5.PubMedCrossRefGoogle Scholar
  83. 83.
    Gnudi S, Butturini L, Ripamonti C, et al. The effects of methotrexate (MTX) on bone. A densitometric study conducted on 59 patients with MTX administered at different doses. Ital J Orthop Traumatol 1988;14:227–31.PubMedGoogle Scholar
  84. 84.
    Wheeler DL, Vander Griend RA, Wronski TJ, et al. The short- and long-term effects of methotrexate on the rat skeleton. Bone 1995;16:215–21.PubMedCrossRefGoogle Scholar
  85. 85.
    Laurindo IM, Mendes FL, Novaes GS, et al. Methotrexate inhibition of bone mineral density increase in growing rabbits: prevention by folinic acid. Clin Exp Rheumatol 2003;21:581–6.PubMedGoogle Scholar
  86. 86.
    Davies JH, Evans BA, Jenney ME, et al. Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children. J Clin Endocrinol. Metab 2003;88:6088–97.PubMedCrossRefGoogle Scholar
  87. 87.
    Vestergaard P, Rejnmark L, Mosekilde L. Methotrexate, azathioprine, cyclosporine, and risk of fracture. Calcif Tissue Int 2006;79:69–75.PubMedCrossRefGoogle Scholar
  88. 88.
    Virolainen P, Inoue N, Nagao M, et al. The effect of a doxorubicin, cisplatin and ifosfamide combination chemotherapy on bone turnover. Anticancer Res 2002;22:1971–5.PubMedGoogle Scholar
  89. 89.
    Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999;17:2365–70.PubMedGoogle Scholar
  90. 90.
    Cross SS. The molecular pathology of new anti-cancer agents. Curr. Diagn. Pathol 2005;11:329–39.CrossRefGoogle Scholar
  91. 91.
    Alibhai SM, Gogov S, Allibhai Z. Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: a systematic literature review. Crit Rev Oncol Hematol 2006;60:201–15.PubMedCrossRefGoogle Scholar
  92. 92.
    Berruti A, Dogliotti L, Terrone C, et al. Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. J Urol 2002;167:2361–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Daniell HW. Osteoporosis after orchiectomy for prostate cancer. J Urol 1997;157:439–44.PubMedCrossRefGoogle Scholar
  94. 94.
    Diamond TH, Bucci J, Kersley JH, et al. Osteoporosis and spinal fractures in men with prostate cancer: risk factors and effects of androgen deprivation therapy. J Urol 2004;172:529–32.PubMedCrossRefGoogle Scholar
  95. 95.
    Greenspan SL, Coates P, Sereika SM, et al. Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 2005;90:6410–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Lopez AM, Pena MA, Hernandez R, et al. Fracture risk in patients with prostate cancer on androgen deprivation therapy. Osteoporos Int 2005;16:707–11.PubMedCrossRefGoogle Scholar
  97. 97.
    Melton LJ III, Alothman KI, Khosla S, et al. Fracture risk following bilateral orchiectomy. J Urol 2003;169:1747–50.PubMedCrossRefGoogle Scholar
  98. 98.
    Morote J, Orsola A, Abascal JM, et al. Bone mineral density changes in patients with prostate cancer during the first 2 years of androgen suppression. J Urol 2006;175:1679–83.PubMedCrossRefGoogle Scholar
  99. 99.
    Morote J, Morin JP, Orsola A, et al. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology 2007;69:500–4.PubMedCrossRefGoogle Scholar
  100. 100.
    Smith MR, Lee WC, Brandman J, et al. Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 2005;23:7897–903.PubMedCrossRefGoogle Scholar
  101. 101.
    Smith MR, Boyce SP, Moyneur E, et al. Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer. J Urol 2006;175:136–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Stoch SA, Parker RA, Chen L, et al. Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 2001;86:2787–91.PubMedCrossRefGoogle Scholar
  103. 103.
    Vordos D, Paule B, Vacherot F, et al. Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer. BJU Int 2004;94:524–7.PubMedCrossRefGoogle Scholar
  104. 104.
    Smith MR, Fallon MA, Lee H, et al. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab 2004;89:3841–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Di Munno O, Delle SA, Rossini M, et al. Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis. Clin Exp Rheumatol 2005;23:137–44.PubMedGoogle Scholar
  106. 106.
    Vestergaard P. Bone loss associated with gastrointestinal disease: prevalence and pathogenesis. Eur J Gastroenterol Hepatol 2003;15:856.CrossRefGoogle Scholar
  107. 107.
    Vestergaard P. Prevalence and pathogenesis of osteoporosis in patients with inflammatory bowel disease. Minerva Med 2004;95:469–80.PubMedGoogle Scholar
  108. 108.
    Hyams JS, Fitzgerald JE, Wyzga N, et al. Relationship of interleukin-1 receptor antagonist to mucosal inflammation in inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1995;21:419–25.PubMedCrossRefGoogle Scholar
  109. 109.
    Hyams JS, Wyzga N, Kreutzer DL, et al. Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study [see comments]. J Pediatr Gastroenterol Nutr 1997;24:289–95.PubMedCrossRefGoogle Scholar
  110. 110.
    Sylvester FA, Wyzga N, Hyams JS, et al. Effect of Crohn’s disease on bone metabolism in vitro: a role for interleukin-6. J Bone Miner Res 2002;17:695–702.PubMedCrossRefGoogle Scholar
  111. 111.
    Canalis E. Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 1996;81:3441–6.PubMedCrossRefGoogle Scholar
  112. 112.
    Patschan D, Loddenkemper K, Buttgereit F. Molecular mechanisms of glucocorticoid-induced osteoporosis. Bone 2001;29:498–505.PubMedCrossRefGoogle Scholar
  113. 113.
    van Staa TP, Laan RF, Barton IP, et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003;48:3224–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Selby PL, Halsey JP, Adams KRH, et al. Cortocosteroids do not alter the threshold for vertebral fracture. J Bone Miner Res 2000;15:952–6.PubMedCrossRefGoogle Scholar
  115. 115.
    Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with systemic and topical corticosteroids. J Intern Med 2005;257:374–84.PubMedCrossRefGoogle Scholar
  116. 116.
    Edsbacker S, Andersson T. Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn’s disease. Clin Pharmacokinet 2004;43:803–21.PubMedCrossRefGoogle Scholar
  117. 117.
    Tromm A, Mollmann H, Barth J, et al. Pharmacokinetics and rectal bioavailability of hydrocortisone acetate after single and multiple administration in healthy subjects and patients. J Clin Pharmacol 2001;41:536–41.PubMedCrossRefGoogle Scholar
  118. 118.
    Daley-Yates PT, Kunka RL, Yin Y, et al. Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal sprays. Eur J Clin Pharmacol 2004;60:265–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Mizuchi A, Miyachi Y, Tamaki K, et al. Percutaneous absorption of betamethasone 17-benzoate measured by radioimmunoassay. J Invest Dermatol 1976;67:279–82.PubMedCrossRefGoogle Scholar
  120. 120.
    Dahlstrom K, Thorsson L, Larsson P, et al. Systemic availability and lung deposition of budesonide via three different nebulizers in adults. Ann Allergy Asthma Immunol 2003;90:226–32.PubMedGoogle Scholar
  121. 121.
    Pedersen S. Do Inhaled Corticosteroids Inhibit Growth in Children? Am J Respir Crit Care Med 2001;164:521–35.PubMedGoogle Scholar
  122. 122.
    Singh SD, Whale C, Houghton N, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003;55:375–81.PubMedCrossRefGoogle Scholar
  123. 123.
    Laan RF, van Riel PL, van de Putte.L.B., et al. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomised controlled study. Ann Intern Med 1993;119:963–8.PubMedGoogle Scholar
  124. 124.
    van Staa TP, Leufkens HGM, Abenhaim L, et al. Fractures and oral corticosteroids: relationship to daily and cumulative dose. Rheumatol 2000;39:1383–9.CrossRefGoogle Scholar
  125. 125.
    Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809–22.PubMedCrossRefGoogle Scholar
  126. 126.
    Hughes MD, Williams PL. Challenges in using observational studies to evaluate adverse effects of treatment. N Engl J Med 2007;356:1705–7.PubMedCrossRefGoogle Scholar
  127. 127.
    Khosla S, Melton LJ III. Clinical practice. Osteopenia. N Engl J Med 2007;356:2293–300.PubMedCrossRefGoogle Scholar
  128. 128.
    van Staa TP, Abenhaim L, Cooper C, et al. Public health impact of adverse bone effects of oral corticosteroids. Br J Clin Pharmacol 2001;51:601–7.PubMedCrossRefGoogle Scholar
  129. 129.
    van Staa TP, Leufkens HGM, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Mineral Res 2000;15:993–1000.CrossRefGoogle Scholar
  130. 130.
    Abramson AS, Delagi EF. Influence of weight-bearing and muscle contraction on disuse osteoporosis. Arch Phys Med Rehab 1961;42:147–51.Google Scholar
  131. 131.
    Dimal HP, Domej W, Leb G, et al. Bone loss in patients with untreated chronic obstructive pulmonary disease is mediated by an increase in bone resorption associated with hypercapnia. J Bone Miner Res 2001;16:2132–41.CrossRefGoogle Scholar
  132. 132.
    Doucet C, Brouty-Boye D, Pottin-Clemenceau C, et al. Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J Clin Invest 1998;101:2129–39.PubMedCrossRefGoogle Scholar
  133. 133.
    Wong CA, Walsh LJ, Smith CJ, et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 2000;355:1399–403.PubMedCrossRefGoogle Scholar
  134. 134.
    Tattersfield AE, Town GI, Johnell O, et al. Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax 2001;56:272–8.PubMedCrossRefGoogle Scholar
  135. 135.
    Bryer HP, Isserow JA, Armstrong EC, et al. Azathioprine alone is bone sparing and does not alter cyclosporin A-induced osteopenia in the rat. J Bone Miner Res 1995;10:132–8.PubMedGoogle Scholar
  136. 136.
    Ferraccioli G, Casatta L, Bartoli E. Increase of bone mineral density and anabolic variables in patients with rheumatoid arthritis resistant to methotrexate after cyclosporin A therapy. J Rheumatol 1996;23:1539–42.PubMedGoogle Scholar
  137. 137.
    Ezaitouni F, Westeel PF, Fardellone P, et al. [Long-term stability of bone mineral density in patients with renal transplant treated with cyclosporine and low doses of corticoids. Protective role of cyclosporine?]. Presse Med 1998;27:705–12.PubMedGoogle Scholar
  138. 138.
    Aroldi A, Tarantino A, Montagnino G, et al. Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study. Transplantation 1997;63:380–6.PubMedCrossRefGoogle Scholar
  139. 139.
    Thiebaud D, Krieg MA, Gillard-Berguer D, et al. Cyclosporine induces high bone turnover and may contribute to bone loss after heart transplantation. Eur J Clin Inves 1996;26:549–55.CrossRefGoogle Scholar
  140. 140.
    Ott R, Bussenius-Kammerer M, Koch CA, et al. Does conversion of immunosuppressive monotherapy from cyclosporine A to tacrolimus improve bone mineral density in long-term stable liver transplant recipients? Transplant Proc 2003;35:3032–4.PubMedCrossRefGoogle Scholar
  141. 141.
    Monegal A, Navasa M, Guanabens N, et al. Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Calcif Tissue Int 2001;68:83–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Campistol JM, Holt DW, Epstein S, et al. Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus. Transpl Int 2005;18:1028–35.PubMedCrossRefGoogle Scholar
  143. 143.
    Cueto-Manzano AM, Konel S, Crowley V, et al. Bone histopathology and densitometry comparison between cyclosporine a monotherapy and prednisolone plus azathioprine dual immunosuppression in renal transplant patients. Transplantation 2003;75:2053–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Cueto-Manzano AM, Konel S, Hutchison AJ, et al. Bone loss in long-term renal transplantation: histopathology and densitometry analysis. Kidney Int 1999;55:2021–9.PubMedCrossRefGoogle Scholar
  145. 145.
    Compeyrot-Lacassagne S, Tyrrell PN, Atenafu E, et al. Prevalence and etiology of low bone mineral density in juvenile systemic lupus erythematosus. Arthritis Rheum 2007;56:1966–73.PubMedCrossRefGoogle Scholar
  146. 146.
    Frei P, Fried M, Hungerbuhler V, et al. Analysis of risk factors for low bone mineral density in inflammatory bowel disease. Digestion 2006;73:40–6.PubMedCrossRefGoogle Scholar
  147. 147.
    Floren CH, Ahren B, Bengtsson M, et al. Bone mineral density in patients with Crohn’s disease during long-term treatment with azathioprine. J Intern Med 1998;243:123–6.PubMedCrossRefGoogle Scholar
  148. 148.
    McIntyre HD, Menzies B, Rigby R, et al. Long-term bone loss after renal transplantation: comparison of immunosuppressive regimens. Clin Transplant 1995;9:20–4.PubMedGoogle Scholar
  149. 149.
    Als OS, Christiansen C, Hellesen C. Prevalence of decreased bone mass in rheumatoid arthritis. Relation to anti-inflammatory treatment. Clin Rheumatol 1984;3:201–8.PubMedCrossRefGoogle Scholar
  150. 150.
    Schorn D. Osteoporosis in the rheumatoid hand–the effects of treatment with D-penicillamine and oral gold salts. S Afr Med J 1983;63:121–3.PubMedGoogle Scholar
  151. 151.
    Hagdrup H, Serup J, Tvedegaard E. Does long-term treatment with D-penicillamine alter calcium and phosphorus metabolism in patients with systemic sclerosis? Acta Derm Venereol 1983;63:447–9.PubMedGoogle Scholar
  152. 152.
    Merker HJ, Franke L, Gunther T. The effect of D-penicillamine of the skeletal development of rat foetuses. Naunyn Schmiedebergs Arch Pharmacol 1975;287:359–76.PubMedCrossRefGoogle Scholar
  153. 153.
    Riede UN. [Cells and matrix of epiphyseal plate after administration of D-penicillamine]. Virchows Arch B Cell Pathol 1971;9:322–32.PubMedGoogle Scholar
  154. 154.
    Trzenschik K, Hahnel H, Muhlbach R, et al. [Animal experiments on the action of D-penicillamine with reference to its effects on the skeletal system]. Dtsch Gesundheitsw 1972;27:289–91.PubMedGoogle Scholar
  155. 155.
    Lakshminarayanan S, Walsh S, Mohanraj M, et al. Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. J Rheumatol 2001;28:102–8.PubMedGoogle Scholar
  156. 156.
    van Schaardenburg D, Valkema R, Dijkmans BA, et al. Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment. Arthritis Rheum 1995;38:334–42.PubMedCrossRefGoogle Scholar
  157. 157.
    Tascioglu F, Oner C, Armagan O. The effect of low-dose methotrexate on bone mineral density in patients with early rheumatoid arthritis. Rheumatol Int 2003;23:231–5.PubMedCrossRefGoogle Scholar
  158. 158.
    Tengstrand B, Hafstrom I. Bone mineral density in men with rheumatoid arthritis is associated with erosive disease and sulfasalazine treatment but not with sex hormones. J Rheumatol 2002;29:2299–305.PubMedGoogle Scholar
  159. 159.
    Marotte H, Pallot-Prades B, Grange L, et al. A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab. Arthritis Res Ther 2007;9:R61.PubMedCrossRefGoogle Scholar
  160. 160.
    Vis M, Voskuyl AE, Wolbink GJ, et al. Bone mineral density in patients with rheumatoid arthritis treated with infliximab. Ann Rheum Dis 2005;64:336–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Vis M, Havaardsholm EA, Haugeberg G, et al. Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1495–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Allali F, Breban M, Porcher R, et al. Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha. Ann Rheum Dis 2003;62:347–9.PubMedCrossRefGoogle Scholar
  163. 163.
    Marzo-Ortega H, McGonagle D, Haugeberg G, et al. Bone mineral density improvement in spondyloarthropathy after treatment with etanercept. Ann Rheum Dis 2003;62:1020–1.PubMedCrossRefGoogle Scholar
  164. 164.
    Bernstein M, Irwin S, Greenberg GR. Maintenance infliximab treatment is associated with improved bone mineral density in Crohn’s disease. Am J Gastroenterol 2005;100:2031–5.PubMedCrossRefGoogle Scholar
  165. 165.
    Pazianas M, Rhim AD, Weinberg AM, et al. The effect of anti-TNF-alpha therapy on spinal bone mineral density in patients with Crohn’s disease. Ann N Y Acad Sci 2006;1068:543–56.PubMedCrossRefGoogle Scholar
  166. 166.
    Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III. Psychosom Med 2004;66:533–7.PubMedCrossRefGoogle Scholar
  167. 167.
    Wong SY, Lau EM, Lynn H, et al. Depression and bone mineral density: is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong). Osteoporosis Int 2005;16:610–5.CrossRefGoogle Scholar
  168. 168.
    Konstantynowicz J, Kadziela-Olech H, Kaczmarski M, et al. Depression in anorexia nervosa: a risk factor for osteoporosis. J Clin Endocrinol Metab 2005;90:5382–5.PubMedCrossRefGoogle Scholar
  169. 169.
    Diem SJ, Blackwell TL, Stone KL, et al. Use of Antidepressants and Rates of Hip Bone Loss in Older Women: The Study of Osteoporotic Fractures. Arch Int Med 2007;167:1240–5.CrossRefGoogle Scholar
  170. 170.
    Haney EM, Chan BKS, Diem SJ, et al. Association of Low Bone Mineral Density With Selective Serotonin Reuptake Inhibitor Use by Older Men. Arch Int Med 2007;167:1246–51.CrossRefGoogle Scholar
  171. 171.
    Bliziotes M, Gunness M, Eshleman A, et al. The role of dopamine and serotonin in regulating bone mass and strength: studies on dopamine and serotonin transporter null mice. J Musculoskelet Neuronal Interact 2002;2:291–5.PubMedGoogle Scholar
  172. 172.
    Warden SJ, Robling AG, Sanders MS, et al. Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 2005;146:685–93.PubMedCrossRefGoogle Scholar
  173. 173.
    Seely EW, Moore TJ, Leboff MS, et al. A single dose of lithium carbonate acutely elevates intact parathyroid hormone levels in humans. Acta Endocrinol (Copenh) 1989;121:174–6.Google Scholar
  174. 174.
    Baastrup PC, Christiansen C, Transbol I. Calcium metabolism in lithium-treated patients. Relation to uni-bipolar dichotomy. Acta Psychiatr Scand 1978;57:124–8.PubMedCrossRefGoogle Scholar
  175. 175.
    Christiansen C, Baastrup PC, Transbol I. Lithium-induced “primary” hyperparathyroidism. Calcif Tissue Res 1977;22(Suppl):341–3.PubMedGoogle Scholar
  176. 176.
    Christiansen C, Baastrup PC, Transbol I. Osteopenia and dysregulation of divalent cations in lithium-treated patients. Neuropsychobiology 1975;1:344–54.PubMedCrossRefGoogle Scholar
  177. 177.
    Eren Y, Yyldyz M, Civi Y, et al. The effects of lithium treatment on bone mineral density of bipolar patients. European Neuropsychopharmacol 2003;13:S249.Google Scholar
  178. 178.
    Christiansen C, Baastrup PC, Transbol I. Development of ‘primary’ hyperparathyroidism during lithium therapy: longitudinal study. Neuropsychobiology 1980;6:280–3.PubMedCrossRefGoogle Scholar
  179. 179.
    Cohen O, Rais T, Lepkifker E, et al. Lithium carbonate therapy is not a risk factor for osteoporosis. Horm Metab Res 1998;30:594–7.PubMedCrossRefGoogle Scholar
  180. 180.
    De Boer J, Wang HJ, Van Blitterswijk C. Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng 2004;10:393–401.PubMedCrossRefGoogle Scholar
  181. 181.
    Pepersack T, Corvilain J, Bergmann P. Effects of lithium on bone resorption in cultured foetal rat long-bones. Eur J Clin Inves 1994;24:400–5.CrossRefGoogle Scholar
  182. 182.
    Pepersack T, Corazza F, Demulder A, et al. Lithium inhibits calcitriol-stimulated formation of multinucleated cells in human long-term marrow cultures. J Bone Miner Res 1994;9:645–50.PubMedGoogle Scholar
  183. 183.
    Brown EM. Lithium induces abnormal calcium-regulated PTH release in dispersed bovine parathyroid cells. J Clin Endocrinol Metab 1981;52:1046–8.PubMedCrossRefGoogle Scholar
  184. 184.
    Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434–41.PubMedCrossRefGoogle Scholar
  185. 185.
    Vestergaard P, Rejnmark L, Mosekilde L. Reduced relative risk of fractures among users of lithium. Calcif Tissue Int 2005;77:1–8.PubMedCrossRefGoogle Scholar
  186. 186.
    Wilting I, de Vries F, Thio BM, et al. Lithium use and the risk of fractures. Bone 2007;40:1252–8.PubMedCrossRefGoogle Scholar
  187. 187.
    Shearn MA. Nonsteroidal anti-inflammatory agents; nonopiate analgesics; drugs used in gout. In: Katzung BG, editor. Basic, clinical pharmacology. Norwalk: Appleton & Lange, 1987. pp. 396–413.Google Scholar
  188. 188.
    Way WL, Way EL. Opioid analgesics & antagonists. In: Katzung BG, editor. Basic, clinical pharmacology. Norwalk: Appleton & Lange, 1987. pp. 336–49.Google Scholar
  189. 189.
    Raisz LG. Physiologic and pathologic roles of prostaglandins and other eicosanoids in bone metabolism. J Nutr 1995;125:2024S–7S.PubMedGoogle Scholar
  190. 190.
    Raisz LG. Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartilage 1999;7:419–21.PubMedCrossRefGoogle Scholar
  191. 191.
    Raisz LG. Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease. Am J Med 2001;110(Suppl 3A):43S–5S.PubMedCrossRefGoogle Scholar
  192. 192.
    Kawaguchi H, Pilbeam CC, Harrison JR, et al. The role of prostaglandins in the regulation of bone metabolism. Clin Orthop Relat Res 1995;313:36–46.PubMedGoogle Scholar
  193. 193.
    Kawaguchi H, Pilbeam CC, Gronowicz G, et al. Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast growth factor. J Clin Invest 1995;96:923–30.PubMedCrossRefGoogle Scholar
  194. 194.
    Hurley MM, Lee SK, Raisz LG, et al. Basic fibroblast growth factor induces osteoclast formation in murine bone marrow cultures. Bone 1998;22:309–16.PubMedCrossRefGoogle Scholar
  195. 195.
    Raisz LG, Fall PM. Biphasic effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: interaction with cortisol. Endocrinology 1990;126:1654–9.PubMedGoogle Scholar
  196. 196.
    Kawaguchi H, Nemoto K, Raisz LG, et al. Interleukin-4 inhibits prostaglandin G/H synthase-2 and cytosolic phospholipase A2 induction in neonatal mouse parietal bone cultures. J Bone Miner Res 1996;11:358–66.PubMedCrossRefGoogle Scholar
  197. 197.
    Kawaguchi H, Pilbeam CC, Vargas SJ, et al. Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae. J Clin Invest 1995;96:539–48.PubMedCrossRefGoogle Scholar
  198. 198.
    Mino T, Sugiyama E, Taki H, et al. Interleukin-1alpha and tumor necrosis factor alpha synergistically stimulate prostaglandin E2-dependent production of interleukin-11 in rheumatoid synovial fibroblasts. Arthritis Rheum 1998;41:2004–13.PubMedCrossRefGoogle Scholar
  199. 199.
    Bell NH, Hollis BW, Shary JR, et al. Diclofenac sodium inhibits bone resorption in postmenopausal women. Am J Med 1994;96:349–53.PubMedCrossRefGoogle Scholar
  200. 200.
    Carbone LD, Tylavsky FA, Cauley JA, et al. Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res 2003;18:1795–802.PubMedCrossRefGoogle Scholar
  201. 201.
    Bauer DC, Orwoll ES, Fox KM, et al. Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1996;11:29–35.PubMedGoogle Scholar
  202. 202.
    Morton DJ, Barrett-Connor EL, Schneider DL. Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study. J Bone Miner Res 1998;13:1924–31.PubMedCrossRefGoogle Scholar
  203. 203.
    Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic Acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis. Calcif Tissue Int 2006;79:84–94.PubMedCrossRefGoogle Scholar
  204. 204.
    Azizi F, Vagenakis AG, Longcope C, et al. Decreased serum testosterone concentration in male heroin and methadone addicts. Steroids 1973;22:467–72.PubMedCrossRefGoogle Scholar
  205. 205.
    Abs R, Verhelst J, Maeyaert J, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab 2000;85:2215–22.PubMedCrossRefGoogle Scholar
  206. 206.
    Finch PM, Roberts LJ, Price L, et al. Hypogonadism in patients treated with intrathecal morphine. Clin J Pain 2000;16:251–4.PubMedCrossRefGoogle Scholar
  207. 207.
    Roberts LJ, Finch PM, Pullan PT, et al. Sex hormone suppression by intrathecal opioids: a prospective study. Clin J Pain 2002;18:144–8.PubMedCrossRefGoogle Scholar
  208. 208.
    Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain 2002;3:377–84.PubMedCrossRefGoogle Scholar
  209. 209.
    Sikharulidze ZD, Kopaliani MG, Kilasoniia LO. Comparative evaluation of clinical symptoms and status of bone metabolism in patients with heroin and buprenorphine addiction in the period of withdrawal. Georgian Med News 2006;134:72–6.PubMedGoogle Scholar
  210. 210.
    Pedrazzoni M, Vescovi PP, Maninetti L, et al. Effects of chronic heroin abuse on bone and mineral metabolism. Acta Endocrinol (Copenh) 1993;129:42–5.Google Scholar
  211. 211.
    Kinjo M, Setoguchi S, Schneeweiss S, et al. Bone mineral density in subjects using central nervous system-active medications. Am J Med 2005;118:1414.PubMedCrossRefGoogle Scholar
  212. 212.
    Lovell SJ, Taira T, Rodriguez E, et al. Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute musculoskeletal pain in the emergency department: a randomized controlled trial. Acad Emerg Med 2004;11:1278–82.PubMedGoogle Scholar
  213. 213.
    Farina C, Gagliardi S. Selective inhibition of osteoclast vacuolar H(+)-ATPase. Curr Pharm Des 2002;8:2033–48.PubMedCrossRefGoogle Scholar
  214. 214.
    Sahara T, Itoh K, Debari K, et al. Specific biological functions of vacuolar-type H(+)-ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts. Anat Rec A Discov Mol Cell Evol Biol 2003;270:152–61.PubMedCrossRefGoogle Scholar
  215. 215.
    Sasaki T. Recent advances in the ultrastructural assessment of osteoclastic resorptive functions. Microsc Res Tech 1996;33:182–91.PubMedCrossRefGoogle Scholar
  216. 216.
    Shibata T, Amano H, Yamada S, et al. Mechanisms of proton transport in isolated rat osteoclasts attached to bone. J Med Dent Sci 2000;47:177–85.PubMedGoogle Scholar
  217. 217.
    Gagliardi S, Nadler G, Consolandi E, et al. 5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides: novel and selective inhibitors of the vacuolar H+-ATPase of osteoclasts with bone antiresorptive activity. J Med Chem 1998;41:1568–73.PubMedCrossRefGoogle Scholar
  218. 218.
    Rzeszutek K, Sarraf F, Davies JE. Proton pump inhibitors control osteoclastic resorption of calcium phosphate implants and stimulate increased local reparative bone growth. J Craniofac Surg 2003;14:301–7.PubMedCrossRefGoogle Scholar
  219. 219.
    Sundquist K, Lakkakorpi P, Wallmark B, et al. Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption. Biochem Biophys Res Commun 1990;168:309–13.PubMedCrossRefGoogle Scholar
  220. 220.
    Visentin L, Dodds RA, Valente M, et al. A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats. J Clin Invest 2000;106:309–18.PubMedCrossRefGoogle Scholar
  221. 221.
    Xu J, Feng HT, Wang C, et al. Effects of Bafilomycin A1: an inhibitor of vacuolar H (+)-ATPases on endocytosis and apoptosis in RAW cells and RAW cell-derived osteoclasts. J Cell Biochem 2003;88:1256–64.PubMedCrossRefGoogle Scholar
  222. 222.
    Mattsson JP, Vaananen K, Wallmark B, et al. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases. Biochim Biophys Acta 1991;1065:261–8.PubMedCrossRefGoogle Scholar
  223. 223.
    Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+,K(+)-ATPase, on bone resorption in humans. Calcif Tissue Int 1993;53:21–5.PubMedCrossRefGoogle Scholar
  224. 224.
    Tran TM, Van den NA, Hendriks JJ, et al. Effects of a proton-pump inhibitor in cystic fibrosis. Acta Paediatr 1998;87:553–8.PubMedCrossRefGoogle Scholar
  225. 225.
    Persson P, Gagnemo-Persson R, Chen D, et al. Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible? Scand J Gastroenterol 1993;28:301–6.PubMedCrossRefGoogle Scholar
  226. 226.
    Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine h(2) receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 2006;79:76–83.PubMedCrossRefGoogle Scholar
  227. 227.
    Yang Y-X, Lewis JD, Epstein S, et al. Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture. JAMA 2006;296:2947–53.PubMedCrossRefGoogle Scholar
  228. 228.
    Vestergaard P, Mollerup CL, Frøkjær VG, et al. Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ 2000;321:598–602.PubMedCrossRefGoogle Scholar
  229. 229.
    Grisso JA, Kelsey JL, O’Brien LA, et al. Risk factors for hip fracture in men. Hip Fracture Study Group. Am J Epidemiol 1997;145:786–93.PubMedGoogle Scholar
  230. 230.
    Adachi Y, Shiota E, Matsumata T, et al. Bone mineral density in patients taking H2-receptor antagonist. Calcif Tissue Int 1998;62:283–5.PubMedCrossRefGoogle Scholar
  231. 231.
    Yamaura K, Yonekawa T, Nakamura T, et al. The histamine H2-receptor antagonist, cimetidine, inhibits the articular osteopenia in rats with adjuvant-induced arthritis by suppressing the osteoclast differentiation induced by histamine. J Pharmacol Sci 2003;92:43–9.PubMedCrossRefGoogle Scholar
  232. 232.
    Lesclous P, Guez D, Saffar JL. Short-term prevention of osteoclastic resorption and osteopenia in ovariectomized rats treated with the H(2) receptor antagonist cimetidine. Bone 2002;30:131–6.PubMedCrossRefGoogle Scholar
  233. 233.
    Lesclous P, Guez D, Baroukh B, et al. Histamine participates in the early phase of trabecular bone loss in ovariectomized rats. Bone 2004;34:91–9.PubMedCrossRefGoogle Scholar
  234. 234.
    Dobigny C, Saffar JL. H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol 1997;173:10–8.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Department of EndocrinologyAalborg University HospitalAalborgDenmark
  2. 2.The Osteoporosis ClinicAarhus AmtssygehusAarhus CDenmark

Personalised recommendations