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Newer Adult Bone Drugs

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Bone Drugs in Pediatrics

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Abstract

This chapter reviews recent advances in established treatments for osteoporosis and newer concepts that have promise for pharmacologic therapy. We cover denosumab, the most recent antiresorptive therapy, and new dosing regimens and formulations of osteoanabolic therapy with parathyroid hormone, parathyroid hormone-related peptide, and their analogs. We also consider new molecules that are currently under development or of interest, including cathepsin K inhibitors, antisclerostin antibody, and nitric oxide.

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References

  1. Warner Chilcott. Actonel® Prescribing Information. Acessed 22 June 2012. Available from: http://actonel.com/global/prescribing_information.pdf.

  2. McClung MR, Miller PD, Brown JP, Zanchetta J, Bolognese MA, Benhamou CL, et al. Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet. Osteoporos Int. 2012;23(1):267–76. Epub 2011/09/29.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Lewiecki EM. Denosumab update. Curr Opin Rheumatol. 2009;21(4):369–73. Epub 2009/05/09.

    Article  PubMed  Google Scholar 

  4. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008;93(6):2149–57. Epub 2008/04/03.

    Article  PubMed  CAS  Google Scholar 

  5. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821–31. Epub 2006/02/24.

    Article  PubMed  CAS  Google Scholar 

  6. Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007;22(12):1832–41. Epub 2007/08/22.

    Article  PubMed  CAS  Google Scholar 

  7. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65. Epub 2009/08/13.

    Article  PubMed  CAS  Google Scholar 

  8. Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55. Epub 2009/08/13.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Bolognese MA, Teglbjaerg CS, Zanchetta JR, Lippuner K, McClung MR, Brandi ML, et al. Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study. J Clin Densitom. 2013;16(2):147–53. Epub 2012/04/24.

    Article  PubMed  Google Scholar 

  10. McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 2013;24(1):227–35. Epub 2012/07/11.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Keaveny T, McClung M, Genant H, Zanchetta J, Kendler D, Brown J, et al. Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Miner Res. 2013;29(1):158–65. Epub 2013/06/25.

    Article  Google Scholar 

  12. Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2009;24(1):153–61. Epub 2008/09/05.

    Article  PubMed  CAS  Google Scholar 

  13. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008;43(2):222–9. Epub 2008/06/10.

    Article  PubMed  CAS  Google Scholar 

  14. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, 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(19):1434–41. Epub 2001/05/11.

    Article  PubMed  CAS  Google Scholar 

  15. Tashjian Jr AH, Chabner BA. Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women. J Bone Miner Res. 2002;17(7):1151–61. Epub 2002/07/05.

    Article  PubMed  CAS  Google Scholar 

  16. Andrews EB, Gilsenan AW, Midkiff K, Sherrill B, Wu Y, Mann BH, et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res. 2012;27(12):2429–37. Epub 2012/09/20.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Cipriani C, Irani D, Bilezikian JP. Safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res. 2012;27(12):2419–28. Epub 2012/11/21.

    Article  PubMed  Google Scholar 

  18. Bilezikian JP. Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr Osteoporos Rep. 2008;6(1):24–30. Epub 2008/04/24.

    Article  PubMed  Google Scholar 

  19. Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, et al. Randomized Teriparatide [human parathyroid hormone (PTH)1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J Clin Endocrinol Metab. 2012;97(9):3097–106. Epub 2012/06/23.

    Article  PubMed  CAS  Google Scholar 

  20. Shiraki M, Sugimoto T, Nakamura T. Effects of a single injection of teriparatide on bone turnover markers in postmenopausal women. Osteoporos Int. 2013;24(1):219–26. Epub 2012/10/25.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Ito M, Fukunaga M, Sone T, Sugimoto T, Shiraki M, Nishizawa Y, Nakamura T. Once weekly teriparatide on hip structure and biomechanical properties. J Bone Miner Res [Internet]. 2011; 26 (Suppl 1). Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=a021c73b-1bde-4a39-a14c-0a7a2823dd12.

  22. Sugimoto T, Shiraki M, Nakano T, Kishimoto H, Ito M, Fukunaga M, et al. Vertebral fracture risk after once-weekly teriparatide injections: follow-up study of Teriparatide Once-Weekly Efficacy Research (TOWER) trial. Curr Med Res Opin. 2013;29(3):195–203. Epub 2012/12/25.

    Article  PubMed  CAS  Google Scholar 

  23. Nakamura Y. [Evidence of osteoporosis treatment with weekly teriparatide injection]. Clin Calcium. 2012;22(3):407–13. Epub 2012/03/01.

    PubMed  CAS  Google Scholar 

  24. Black DM, Bouxsein ML, Palermo L, McGowan JA, Newitt DC, Rosen E, et al. Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab. 2008;93(6):2166–72. Epub 2008/03/20.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003;349(13):1207–15. Epub 2003/09/23.

    Article  PubMed  CAS  Google Scholar 

  26. Gopalakrishnan V, Hwang, S., Loughrey, H. Administration of ThPTH to humans using Macroflux transdermal technology results in the rapid delivery of biologically active PTH. J Bone Miner Res [Internet]. 2004; 19(Suppl 1). Available from: http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey=%7B0D89B6BF-D307-47AB-ACD6-7494CAB6B769%7D%26SKey=%7B1DE07408-047F-4D36-898B-BD6629C81863%7D%26MKey=%7B96915C07-D110-439D-BF0C-C23CD3392D2D%7D%26AKey=%7BD0C01D4F-E23B-45E2-ACD4-0AF8AC866B8B%7D.

  27. Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, et al. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2010;95(1):151–8. Epub 2009/10/28.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Daddona PE, Matriano JA, Mandema J, Maa YF. Parathyroid hormone (1-34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis. Pharm Res. 2011;28(1):159–65. Epub 2010/06/23.

    Article  PubMed  CAS  Google Scholar 

  29. Farra R, Sheppard Jr NF, McCabe L, Neer RM, Anderson JM, Santini Jr JT, et al. First-in-human testing of a wirelessly controlled drug delivery microchip. Science Transl Med. 2012;4(122):122ra21. Epub 2012/02/22.

    Google Scholar 

  30. Wysolmerski JJ, Stewart AF. The physiology of parathyroid hormone-related protein: an emerging role as a developmental factor. Annu Rev Physiol. 1998;60:431–60. Epub 1998/04/29.

    Article  PubMed  CAS  Google Scholar 

  31. Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. 2000;342(3):177–85. Epub 2000/01/20.

    Article  PubMed  CAS  Google Scholar 

  32. Hock JM, Fonseca J, Gunness-Hey M, Kemp BE, Martin TJ. Comparison of the anabolic effects of synthetic parathyroid hormone-related protein (PTHrP) 1-34 and PTH 1-34 on bone in rats. Endocrinology. 1989;125(4):2022–7. Epub 1989/10/01.

    Article  PubMed  CAS  Google Scholar 

  33. Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003;88(2):569–75. Epub 2003/02/08.

    Article  PubMed  CAS  Google Scholar 

  34. Horwitz MJ, Tedesco MB, Garcia-Ocana A, Sereika SM, Prebehala L, Bisello A, et al. Parathyroid hormone-related protein for the treatment of postmenopausal osteoporosis: defining the maximal tolerable dose. J Clin Endocrinol Metab. 2010;95(3):1279–87. Epub 2010/01/12.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Horwitz MJ, Augustine M, Kahn L, Martin E, Oakley CC, Carneiro RM, et al. A comparison of parathyroid hormone-related protein (1–36) and parathyroid hormone (1–34) on markers of bone turnover and bone density in postmenopausal women: The PrOP study. J Bone Miner Res. 2013;28(11):2266–76. Epub 2013/05/11.

    Article  PubMed  CAS  Google Scholar 

  36. Hattersley G, Bilezikian, J.P., Guerriero, J., Kumar, P., Zanchetta, J., Lyttle, C.R., O'Dea, L.S. Bone Anabolic Efficacy and Safety of BA058, a Novel Analog of hPTHrP: results from a phase 2 clinical trial in postmenopausal women with osteoporosis. Endocr Rev [Internet]. 2012; 33(03). Available from: http://edrv.endojournals.org/cgi/content/meeting_abstract/33/03_MeetingAbstracts/OR08-1.

  37. Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003;349(13):1216–26. Epub 2003/09/23.

    Article  PubMed  CAS  Google Scholar 

  38. Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res. 2005;20(11):1905–11. Epub 2005/10/20.

    Article  PubMed  CAS  Google Scholar 

  39. Walker MD, Cusano NE, Sliney Jr J, Romano M, Zhang C, McMahon DJ, et al. Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine. 2012;44(1):237–46. Epub 2012/10/27.

    Article  PubMed  Google Scholar 

  40. Cosman F, Eriksen EF, Recknor C, Miller PD, Guanabens N, Kasperk C, et al. Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] in postmenopausal osteoporosis. J Bone Miner Res. 2011;26(3):503–11. Epub 2010/09/04.

    Article  PubMed  CAS  Google Scholar 

  41. Gasser JA, Ingold P, Venturiere-Rebmann A, Green JR. Chronic subcutaneous, but not single intravenous, dosing of rats with bisphosphonates results in reduced bone anabolic response to PTH. J Bone Miner Res [Internet]. 2006; 21(Suppl 1). Available from: http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey=%7BA9907BBE-DF9A-4466-8343-562C602B13C4%7D&SKey=%7BACBF01A6-69A9-4204-8600-ADF1DDE684A3%7D&MKey=%7BFC197A55-D8DD-4F3D-9994-290B64584CCB%7D&AKey=%7BD0C01D4F-E23B-45E2-ACD4-0AF8AC866B8B%7D.

  42. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19(7):1059–66. Epub 2004/06/05.

    Article  PubMed  CAS  Google Scholar 

  43. McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 2012;24(1):227–35. Epub 2012/07/11.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Lee SK, Lorenzo JA. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology. 1999;140(8):3552–61. Epub 1999/08/05.

    PubMed  CAS  Google Scholar 

  45. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology. 2001;142(12):5050–5. Epub 2001/11/20.

    Article  PubMed  CAS  Google Scholar 

  46. Huang JC, Sakata T, Pfleger LL, Bencsik M, Halloran BP, Bikle DD, et al. PTH differentially regulates expression of RANKL and OPG. J Bone Miner Res. 2004;19(2):235–44. Epub 2004/02/19.

    Article  PubMed  CAS  Google Scholar 

  47. O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, et al. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One. 2008;3(8):e2942. Epub 2008/08/14.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Costa AG, Cremers S, Rubin MR, McMahon DJ, Sliney Jr J, Lazaretti-Castro M, et al. Circulating sclerostin in disorders of parathyroid gland function. J Clin Endocrinol Metab. 2011;96(12):3804–10. Epub 2011/09/23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Seeman E, Libanati C, Austin M, Chapurlat R, Boyd SK, Zebaze R, et al. The Transitory Increase in PTH Following Denosumab Administration is Associated with Reduced Intracortical Porosity: A Distinctive Attribute of Denosumab Therapy. J Bone Miner Res [Internet]. 2011; 26(Suppl 1). Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=e70a7c81-16c2-4021-8f86-d900f6711f94.

  50. Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013;382(9886):50–6. Epub 2013/05/21.

    Article  PubMed  CAS  Google Scholar 

  51. Costa AG, Cusano NE, Silva BC, Cremers S, Bilezikian JP. Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis. Nat Rev Rheumatol. 2011;7(8):447–56. Epub 2011/06/15.

    Article  PubMed  CAS  Google Scholar 

  52. Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996;273(5279):1236–8. Epub 1996/08/30.

    Article  PubMed  CAS  Google Scholar 

  53. Chavassieux P, Seeman E, Delmas PD. Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev. 2007;28(2):151–64. Epub 2007/01/04.

    Article  PubMed  CAS  Google Scholar 

  54. Yamashita DS, Dodds RA. Cathepsin K and the design of inhibitors of cathepsin K. Curr Pharm Des. 2000;6(1):1–24. Epub 2000/01/19.

    Article  PubMed  CAS  Google Scholar 

  55. Kumar S, Dare L, Vasko-Moser JA, James IE, Blake SM, Rickard DJ, et al. A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys. Bone. 2007;40(1):122–31. Epub 2006/09/12.

    Article  PubMed  CAS  Google Scholar 

  56. Guo J, Bot I, de Nooijer R, Hoffman SJ, Stroup GB, Biessen EA, et al. Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice. Cardiovasc Res. 2009;81(2):278–85. Epub 2008/11/19.

    Article  PubMed  CAS  Google Scholar 

  57. Seeman E. Advances in therapeutics: meeting report from the 31st Annual Meeting of the American Society for Bone and Mineral Research: September 11-15, 2009 in Denver, Colorado. IBMS BoneKEy. 2009;6:496–502.

    Article  Google Scholar 

  58. Nagase S, Ohyama M, Hashimoto Y, Small M, Kuwayama T, Deacon S. Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple-dose, phase 1 study. J Clin Pharmacol. 2012;52(3):306–18. Epub 2011/07/02.

    Article  PubMed  CAS  Google Scholar 

  59. Eastell R, Nagase S, Ohyama M, Small M, Sawyer J, Boonen S, et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J Bone Miner Res. 2011;26(6):1303–12. Epub 2011/02/12.

    Article  PubMed  CAS  Google Scholar 

  60. Eastell R, Nagase S, Small M, Ohyama M, Kuwayama T, Manako J, et al. Effect of the Cathepsin K Inhibitor, ONO-5334, on biochemical markers of bone turnover in the treatment of postmenopausal osteopenia or osteoporosis. J Bone Miner Res [Internet]. 2010; 25(Suppl 1). Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=79d3b619-90d1-4886-bade-c7d06ac08143.

  61. Quintanilla-Dieck MJ, Codriansky K, Keady M, Bhawan J, Runger TM. Expression and regulation of cathepsin K in skin fibroblasts. Exp Dermatol. 2009;18(7):596–602. Epub 2009/05/28.

    Article  PubMed  CAS  Google Scholar 

  62. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010;25(5):937–47. Epub 2009/10/31.

    PubMed  Google Scholar 

  63. Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011;26(2):242–51. Epub 2010/08/27.

    Article  PubMed  CAS  Google Scholar 

  64. Alatalo SL, Ivaska KK, Waguespack SG, Econs MJ, Vaananen HK, Halleen JM. Osteoclast-derived serum tartrate-resistant acid phosphatase 5b in Albers-Schonberg disease (type II autosomal dominant osteopetrosis). Clin Chem. 2004;50(5):883–90. Epub 2004/03/16.

    Article  PubMed  CAS  Google Scholar 

  65. Neele SJ, Evertz R, De Valk-De Roo G, Roos JC, Netelenbos JC. Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone. 2002;30(4):599–603. Epub 2002/04/06.

    Article  PubMed  CAS  Google Scholar 

  66. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80. Epub 2011/02/04.

    Article  PubMed  CAS  Google Scholar 

  67. Bauer DC. Discontinuation of odanacatib and other osteoporosis treatments: here today and gone tomorrow? J Bone Miner Res. 2011;26(2):239–41. Epub 2011/01/22.

    Article  PubMed  Google Scholar 

  68. Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–80. Epub 2013/01/23.

    Article  PubMed  CAS  Google Scholar 

  69. Lewiecki EM. Sclerostin: a novel target for intervention in the treatment of osteoporosis. Discov Med. 2011;12(65):263–73. Epub 2011/10/28.

    PubMed  Google Scholar 

  70. Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol. 2007;19(4):376–82. Epub 2007/06/07.

    Article  PubMed  CAS  Google Scholar 

  71. Zhang W, Drake MT. Potential role for therapies targeting DKK1, LRP5, and serotonin in the treatment of osteoporosis. Curr Osteoporos Rep. 2012;10(1):93–100. Epub 2012/01/03.

    Article  PubMed  Google Scholar 

  72. Glantschnig H, Hampton RA, Lu P, Zhao JZ, Vitelli S, Huang L, et al. Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem. 2010;285(51):40135–47. Epub 2010/10/12.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010;25(5):948–59. Epub 2010/03/05.

    Article  PubMed  CAS  Google Scholar 

  74. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24(4):578–88. Epub 2008/12/04.

    Article  PubMed  CAS  Google Scholar 

  75. Marenzana M, Greenslade K, Eddleston A, Okoye R, Marshall D, Moore A, et al. Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone. Arthritis Rheum. 2011;63(8):2385–95. Epub 2011/04/13.

    Article  PubMed  CAS  Google Scholar 

  76. Tian X, Jee WS, Li X, Paszty C, Ke HZ. Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. Bone. 2011;48(2):197–201. Epub 2010/09/21.

    Article  PubMed  CAS  Google Scholar 

  77. Li X, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Grisanti M, et al. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. J Bone Miner Res. 2010;25(12):2647–56. Epub 2010/07/20.

    Article  PubMed  Google Scholar 

  78. Li X, Ominsky MS, Warmington KS, Niu QT, Asuncion FJ, Barrero M, et al. Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats. Endocrinology. 2011;152(9):3312–22. Epub 2011/07/08.

    Article  PubMed  CAS  Google Scholar 

  79. Eddleston A, Marenzana M, Moore AR, Stephens P, Muzylak M, Marshall D, et al. A short treatment with an antibody to sclerostin can inhibit bone loss in an ongoing model of colitis. J Bone Miner Res. 2009;24(10):1662–71. Epub 2009/05/08.

    Article  PubMed  CAS  Google Scholar 

  80. Ominsky MS, Li C, Li X, Tan HL, Lee E, Barrero M, et al. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J Bone Miner Res. 2011;26(5):1012–21. Epub 2011/05/05.

    Article  PubMed  CAS  Google Scholar 

  81. Agholme F, Li X, Isaksson H, Ke HZ, Aspenberg P. Sclerostin antibody treatment enhances metaphyseal bone healing in rats. J Bone Miner Res. 2010;25(11):2412–8. Epub 2010/05/26.

    Article  PubMed  CAS  Google Scholar 

  82. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26(1):19–26. Epub 2010/07/02.

    Article  PubMed  CAS  Google Scholar 

  83. McClung; MR, Boonen; S, Jacques P. Brown, Adolfo Diez-Perez, Bente Langdahl, Jean-Yves Reginster, et al. Inhibition of sclerostin with AMG 785 in postmenopausal women with low bone mineral density: phase 2 trial results. J Bone Miner Res [Internet]. 2012; 27(Suppl 1). Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=9fa27a06-d9b5-4429-a95f-517048985173.

  84. http://clinicaltrials.gov/ct2/show/NCT00907296?term=amg+785&rank=1. Accessed on 09/09/2011.

  85. http://clinicaltrials.gov/ct2/show?term=amg+785&rank=2. Accessed on 09/09/2011.

  86. Benson C, Robins D, Recker R, Alam J, Chiang A, Mitlak B, et al. Effect of blosozumab on bone mineral density: results of a phase 2 study of postmenopausal women with low bone mineral density. Presented at the European Calcified Tissue Society Conference ECTS Bone Abstracts [Internet]. 2013; 1. Available from: http://www.bone-abstracts.org/ba/0001/ba0001OC5.3.htm.

  87. Matsumoto T, Robins R, Alam J, Chiang A, Hu L, Mitlak B, et al. Effect of Blosozumab on bone mineral density in Japanese and non-Japanese postmenopausal women with low bone mineral density. IBMS BoneKEy [Internet]. 2013; 10. Available from: http://www.nature.com/bonekey/knowledgeenvironment/2013/130522/bonekey201367/pdf/bonekey201367.pdf.

  88. Brandi ML, Hukkanen M, Umeda T, Moradi-Bidhendi N, Bianchi S, Gross SS, et al. Bidirectional regulation of osteoclast function by nitric oxide synthase isoforms. Proc Natl Acad Sci U S A. 1995;92(7):2954–8. Epub 1995/03/28.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  89. Wimalawansa SJ. Nitric oxide and bone. Ann N Y Acad Sci. 2010;1192:391–403. Epub 2010/04/16.

    Article  PubMed  CAS  Google Scholar 

  90. Rejnmark L, Vestergaard P, Mosekilde L. Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res. 2006;21(11):1811–7. Epub 2006/10/24.

    Article  PubMed  CAS  Google Scholar 

  91. Jamal SA, Browner WS, Bauer DC, Cummings SR. Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res. 1998;13(11):1755–9. Epub 1998/11/03.

    Article  PubMed  CAS  Google Scholar 

  92. Pouwels S, Lalmohamed A, van Staa T, Cooper C, Souverein P, Leufkens HG, et al. Use of organic nitrates and the risk of hip fracture: a population-based case-control study. J Clin Endocrinol Metab. 2010;95(4):1924–31. Epub 2010/02/05.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Jamal SA, Reid LS, Hamilton CJ. The effects of organic nitrates on osteoporosis: a systematic review. Osteoporos Int. 2013;24(3):763–70. Epub 2013/01/12.

    Article  PubMed  CAS  Google Scholar 

  94. Jamal SA, Cummings SR, Hawker GA. Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial. J Bone Miner Res. 2004;19(9):1512–7. Epub 2004/08/18.

    Article  PubMed  CAS  Google Scholar 

  95. Jamal SA, Hamilton CJ, Eastell R, Cummings SR. Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA. 2011;305(8):800–7. Epub 2011/02/24.

    Article  PubMed  CAS  Google Scholar 

  96. Nabhan AF, Rabie NH. Isosorbide mononitrate versus alendronate for postmenopausal osteoporosis. Int J Gynaecol Obstet. 2008;103(3):213–6. Epub 2008/09/23.

    Article  PubMed  CAS  Google Scholar 

  97. Wimalawansa SJ, Grimes JP, Wilson AC, Hoover DR. Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss. J Clin Endocrinol Metab. 2009;94(9):3356–64. Epub 2009/06/25.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, PH8W-864, New York, NY, 10032, USA

    Natalie E. Cusano M.D., Aline G. Costa M.D., Barbara C. Silva M.D., Ph.D. & John P. Bilezekian M.D.

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  1. Natalie E. Cusano M.D.
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  2. Aline G. Costa M.D.
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  3. Barbara C. Silva M.D., Ph.D.
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  4. John P. Bilezekian M.D.
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Correspondence to Natalie E. Cusano M.D. .

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  1. Department of Orthopaedic Surgery, University of Texas Medical Branch, Galveston, Texas, USA

    Gordon L. Klein

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Cusano, N.E., Costa, A.G., Silva, B.C., Bilezekian, J.P. (2014). Newer Adult Bone Drugs. In: Klein, G. (eds) Bone Drugs in Pediatrics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7436-5_12

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