title: Optimal bone health management strategies in patients with prostate cancer.
abstract: Bone health is affected in patients with prostate cancer, both by the disease and its treatment. Metastases to bone leads to pain, fractures, and spinal cord compression; bone loss due to androgen deprivation therapy (ADT) leads to osteoporosis and its complications. Both these scenarios are a major cause of morbidity and adversely affect the quality of life of these patients. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease. An understanding of the complex interplay between osteoclasts, osteoblasts, receptor activator of nuclear factor κB (RANK), and various other tyrosine kinases involved in the pathophysiology of bone metastases is essential. Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases. This article discusses the pathophysiology of bone metastases and bone loss due to ADT in prostate cancer, role of biomarkers, newer modalities of imaging, World Health Organization (WHO)/FRAX nomogram in evaluation of these patients, utility of currently available drugs and evidence supporting their use, and newer therapeutic agents like alpha-emitting Radium-223, endothelin-A receptor antagonists (Atrasentan and Zibotentan) and the proto-oncogene tyrosine-protein kinase (SRC) inhibitor, Dasatinib.
authors: Department of Urooncology, Tata Memorial Centre, Mumbai, Maharashtra, India.
authors: Gagan
authors: G
authors: Prakash
authors: Gagan
authors: G
authors: Gautam
keywords: Bisphosphonates; bone metastasis; osteoclasts; prostate cancer; skeletal related events; zoledronic acid
references: J Natl Cancer Inst. 2002 Oct 2;94(19):1458-68
references: 12359855
references: Osteoporos Int. 2005 Jul;16(7):737-42
references: 15455194
references: Lancet Oncol. 2009 Sep;10(9):872-6
references: 19674936
references: J Clin Oncol. 2005 Nov 1;23(31):7897-903
references: 16258089
references: J Bone Miner Res. 2005 Jul;20(7):1185-94
references: 15940371
references: Clin Oncol (R Coll Radiol). 2006 Dec;18(10):747-60
references: 17168210
references: J Nucl Med. 2001 Dec;42(12):1800-4
references: 11752076
references: Osteoporos Int. 2005 Feb;16(2):155-62
references: 15175845
references: Cancer Res. 2001 Jul 15;61(14):5644-51
references: 11454719
references: Nat Med. 1995 Sep;1(9):944-9
references: 7585222
references: J Bone Miner Res. 2008 Jun;23(6):826-36
references: 18558816
references: Skeletal Radiol. 1990;19(2):113-6
references: 2321040
references: Ann Intern Med. 2008 May 6;148(9):680-4
references: 18458281
references: Bone. 2004 Nov;35(5):1029-37
references: 15542027
references: Clin Chem. 1999 Aug;45(8 Pt 2):1359-68
references: 10430819
references: Cancer. 2004 Mar 1;100(5):892-9
references: 14983482
references: Eur Urol. 2010 Apr;57(4):551-8
references: 20034730
references: J Urol. 2010 Oct;184(4):1316-21
references: 20723926
references: Lancet. 2011 Mar 5;377(9768):813-22
references: 21353695
references: J Urol. 2004 Dec;172(6 Pt 1):2137-44
references: 15538219
references: Eur Urol. 1993;24(2):286-90
references: 8375452
references: N Engl J Med. 2004 Apr 15;350(16):1655-64
references: 15084698
references: Lancet. 2012 Jan 7;379(9810):39-46
references: 22093187
references: J Clin Oncol. 2010 Dec 10;28(35):5132-9
references: 21060033
references: J Nucl Med. 1993 Nov;34(11):1839-44
references: 8229221
references: J Clin Oncol. 2004 Jul 15;22(14):2942-53
references: 15254062
references: J Urol. 1999 Apr;161(4):1219-22
references: 10081873
references: J Clin Oncol. 2009 Jul 10;27(20):3319-24
references: 19414670
references: J Urol. 2003 Dec;170(6 Pt 2):S59-63; discussion S64
references: 14610412
references: AJR Am J Roentgenol. 1990 Nov;155(5):1043-8
references: 2120933
references: Clin Cancer Res. 2006 Feb 15;12(4):1221-8
references: 16489077
references: Ann N Y Acad Sci. 2007 Nov;1117:209-57
references: 18056045
references: Bone. 2004 Aug;35(2):375-82
references: 15268886
references: Mol Cancer Ther. 2010 May;9(5):1147-57
references: 20423991
references: Cancer. 2000 Jun 15;88(12 Suppl):2952-60
references: 10898339
references: Urology. 2001 Jan;57(1):127-32
references: 11164157
references: Lancet. 2001 Feb 3;357(9253):336-41
references: 11210994
references: Eur Urol. 2009 May;55(5):1112-23
references: 19042080
references: Cancer. 1997 Oct 15;80(8 Suppl):1652-60
references: 9362432
references: Cancer Treat Rev. 2010 Apr;36(2):177-84
references: 20015594
references: Osteoporos Int. 2005 Nov;16(11):1330-8
references: 15928804
references: J Bone Miner Res. 2004 Jun;19(6):893-9
references: 15125788
references: BJU Int. 2009 Dec;104(11):1637-40
references: 19549260
references: J Clin Endocrinol Metab. 2004 Aug;89(8):3841-6
references: 15292315
references: AJR Am J Roentgenol. 2001 Jul;177(1):229-36
references: 11418435
references: Prostate. 2005 Oct 1;65(2):178-87
references: 15948151
references: J Urol. 2009 Aug;182(2):509-15; discussion 515-6
references: 19524963
references: J Natl Cancer Inst. 2007 May 16;99(10):765-76
references: 17505072
references: BJU Int. 2004 Aug;94(3):268-71
references: 15291850
references: J Oral Maxillofac Surg. 2007 Mar;65(3):369-76
references: 17307580
references: Osteoporos Int. 2006;17(11):1577-83
references: 16896511
references: J Nucl Med. 2006 Feb;47(2):287-97
references: 16455635
references: J Clin Oncol. 2007 Aug 1;25(22):3281-7
references: 17664475
references: J Clin Oncol. 2007 Dec 20;25(36):5837-8; author reply 5838-9
references: 18089886
references: J Clin Oncol. 2003 Dec 1;21(23):4277-84
references: 14581438
references: J Clin Oncol. 2003 Sep 1;21(17):3335-42
references: 12947070
references: Cancer. 2003 Oct 15;98(8):1735-44
references: 14534891
references: Osteoporos Int. 2005 Jul;16(7):799-804
references: 15502959
references: Mol Cancer Ther. 2010 Jun;9(6):1629-37
references: 20484016
references: Semin Nucl Med. 2010 Mar;40(2):89-104
references: 20113678
references: Clin Oncol (R Coll Radiol). 2005 Sep;17(6):430-4
references: 16149286
references: J Urol. 2008 Jan;179(1):152-5
references: 18001802
references: Clin Cancer Res. 2009 Dec 1;15(23):7421-8
references: 19920114
references: J Clin Oncol. 2003 Aug 15;21(16):3150-7
references: 12915606
references: Indian J Urol. 2012 Oct;28(4):399-404
references: 23450674
references: J Clin Oncol. 2011 Sep 20;29(27):3705-14
references: 21860001
references: J Clin Oncol. 2009 Apr 1;27(10):1564-71
references: 19237632
references: J Urol. 2000 Oct;164(4):1248-53
references: 10992374
references: N Engl J Med. 2009 Aug 20;361(8):745-55
references: 19671656