Painful Osseous Metastases

Pain Physician

Volumn 14, Issue 4, 2011, Pages

  Smith, Howard S ^a  

^a ALBANY MEDICAL COLLEGE   (United States)

Author keywords

Bone pain; Cancer pain; Metastasis; Osseous metastasis; Radiation therapy; Radiopharmaceuticals

Indexed keywords

ACTIVIN; ANTICONVULSIVE AGENT; B CELL ACTIVATING FACTOR; BISPHOSPHONIC ACID DERIVATIVE; BOSUTINIB; CATHEPSIN K INHIBITOR; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; DASATINIB; DENOSUMAB; DOCETAXEL; ENDOTHELIN; ETIDRONIC ACID RE 186; LEXIDRONAM SAMARIUM SM 153; NARCOTIC ANALGESIC AGENT; NERVE GROWTH FACTOR RECEPTOR; NONSTEROID ANTIINFLAMMATORY AGENT; ODANACATIB; OPIATE; OSTEOPROTEGERIN; PHOSPHORUS 32; PLACEBO; RHENIUM 188; SALCATONIN; SARACATINIB; STRONTIUM 89; TRANSFORMING GROWTH FACTOR BETA; UNINDEXED DRUG; VANILLOID RECEPTOR 1; WNT PROTEIN; ZOLEDRONIC ACID;

ACUTE LYMPHOBLASTIC LEUKEMIA; BONE CANCER; BONE DISEASE; BONE METASTASIS; BONE NECROSIS; BONE PAIN; BREAST CANCER; BREAST METASTASIS; CANCER HORMONE THERAPY; CANCER PAIN; CANCER RADIOTHERAPY; CANCER RISK; CASTRATION RESISTANT PROSTATE CANCER; CHRONIC MYELOID LEUKEMIA; CHRONIC PAIN; COGNITIVE DEFECT; COMPARATIVE EFFECTIVENESS; CRYOABLATION; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG ABSORPTION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG PENETRATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; HEAD AND NECK CANCER; HOT FLUSH; HUMAN; KIDNEY CANCER; KYPHOPLASTY; LEUKOCYTE COUNT; LEUKOPENIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; METASTASIS; MULTIPLE MYELOMA; NEPHROTOXICITY; NEUROPATHIC PAIN; NONHUMAN; OSTEOCLASTOGENESIS; OSTEOLYSIS; PANCREAS CANCER; PERCUTANEOUS VERTEBROPLASTY; PROSTATE CANCER; RADIATION DOSE; RADIOFREQUENCY ABLATION; RECOMMENDED DRUG DOSE; REPEATED DRUG DOSE; REVIEW; RISK BENEFIT ANALYSIS; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; SKIN MANIFESTATION; SOLID TUMOR; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TREATMENT RESPONSE;

BONE NEOPLASMS; HUMANS; PAIN; PAIN MANAGEMENT;

EID: 79960871485     PISSN: 15333159     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (315)

1. Boyle P, Levin B (eds). World Cancer Report 2008. International Agency for Research on Cancer, Lyon, France, 2008.
2. Berruti A, Dogliotti L, Bitossi R, Fasolis G, Gorzegno G, Bellina M, Torta M, Porpiglia F, Fontana D, Angeli A. Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: Predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000; 164:1248-1253.
3. Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: A longitudinal followup study of symptom prevalence, severity and etiology. Pain 2001; 93:247-257.
4. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: A systematic review of the past 40 years. Ann Oncol 2007; 18:1437-1449.
5. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. High prevalence of pain in patients with cancer in a large population-based study in The Netherlands. Pain 2007; 132:312-320.
6. Farhanghi M, Holmes RA, Volkert WA, Logan KW, Singh A. Samarium-153-EDTMP: Pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. J Nucl Med 1992; 33:1451-1458.
7. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987; 55:61-66.
8. Delaney A, Fleetwood-Walker SM, Colvin LA, Fallon M. Translational medicine: Cancer pain mechanisms and management. Br J Anaesth 2008; 101:87-94.
9. Walley J, Colvin LA, Fallon MT, Murray G, Clausen E. Characterisation of cancer-induced bone pain. In Proceedings of The British Pain Society. 2006; A45.
10. Payne R, Janjan N. Management of metastatic bone pain. Assessment and treatment of cancer pain. In: Payne R, Patt RB, Hill CS (eds). Progress in Pain Research and Management. Vol 12. IASP Press, Seattle, 1998.
11. Janjan NA, Payne R, Gillis T, Podoloff D, Libshitz HI, Lenzi R, Theriault R, Martin C, Tasko A. Presenting symptoms in patients referred to a multidisciplinary clinic for bone metastases. J Pain Symptom Manage 1998; 16:171-178.
12. Fulfaro F, Casuccio A, Ticozzi C, Ripamonti C. The role of bisphosphonates in the treatment of painful metastatic bone disease: A review of phase III trials. Pain 1998; 78:157-169.
13. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone, plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: A Canadian randomized trial with palliative end point. J Clin Oncol 1996; 14:1756-1764.
14. Smith H, Navani A, Fishman SM. Radiopharmaceuticals for palliation of painful osseous metastases. Am J Hosp Palliat Care 2004; 21:303-313.
15. Gulati A, Khelemsky Y, Loh J, Puttanniah V, Malhotra V, Cubert K. The use of lumbar sympathetic blockade at L4 for management of malignancy-related bladder spasms. Pain Physician 2011; 14:305-310.
16. Hayek SM, Deer TR, Pope JE, Panchal SJ, Patel VB. Intrathecal therapy for cancer and non-cancer pain. Pain Physician 2011; 14:219-248.
17. Deer TR, Smith HS, Burton AW, Pope JE, Doleys DM, Levy RM, Staats PS, Wallace MS, Webster LR, Rauck Rl, Cousins M. Comprehensive consensus-based guidelines on intrathecal drug delivery systems in the treatment of pain caused by cancer pain. Pain Physician 2011; 14:E283-E312.
18. Colson J, Koyyalagunta D, Falco FJ, Manchikanti L. A systematic review of observational studies on the effectiveness of opioid therapy for cancer pain. Pain Physician 2011; 14:E85-E102.
19. Buvanendran A, Ali A, Stoub TR, Kroin JS, Tuman KJ. Brain activity associated with chronic cancer pain. Pain Physician 2010; 13:E337-E342.
20. Deer TR, Smith HS, Cousins M, Doleys DM, Levy RM, Rathmell JP, Staats PS, Wallace M, Webster LR. Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery. Pain Physician 2010; 13:E175-E213.
21. Manchikanti L. Singh V, Datta S, Cohen SP, Hirsch JA. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician 2009; 12:E35-E70.
22. Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, Buenaventura RM, Conn A, Datta S, Derby R, Falco FJE, Erhart S, Diwan S, Hayek SM, Helm S, Parr AT, Schultz DM, Smith HS, Wolfer LR, Hirsch JA. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician 2009; 12:699-802.
23. Manchikanti L, Boswell MV, Singh V, Derby R, Fellows B, Falco FJE, Datta S, Smith HS, Hirsch JA. Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain. Pain Physician 2009; 12:E71-E120.
24. Manchikanti L, Boswell MV, Datta S, Fellows B, Abdi S, Singh V, Benyamin RM, Falco FJE, Helm S, Hayek S, Smith HS. Comprehensive review of therapeutic interventions in managing chronic spinal pain. Pain Physician 2009; 12:E123-E198.
25. Conn A, Buenaventura R, Datta S, Abdi S, Diwan S. Systematic review of caudal epidural injections in the management of chronic low back pain. Pain Physician 2009; 12:109-135.
26. Parr AT, Diwan S, Abdi S. Lumbar interlaminar epidural injections in managing chronic low back and lower extremity pain: A systematic review. Pain Physi cian 2009; 12:163-188.
27. Benyamin RM, Singh V, Parr AT, Conn A, Diwan S, Abdi S. Systematic review of the effectiveness of cervical epidurals in the management of chronic neck pain. Pain Physician 2009; 12:137-157.
28. Buenaventura RM, Datta S, Abdi S, Smith HS. Systematic review of therapeutic lumbar transforaminal epidural steroid injections. Pain Physician 2009; 12:233-251.
29. Atluri S, Datta S, Falco FJE, Lee M. Systematic review of diagnostic utility and therapeutic effectiveness of thoracic facet joint interventions. Pain Physician 2008; 11:611-629.
30. Falco FJE, Erhart S, Wargo BW, Bryce DA, Atluri S, Datta S, Hayek SM. Systematic review of diagnostic utility and therapeutic effectiveness of cervical facet joint interventions. Pain Physician 2009; 12:323-344.
31. Datta S, Lee M, Falco FJE, Bryce DA, Hayek SM. Systematic assessment of diagnostic accuracy and therapeutic utility of lumbar facet joint interventions. Pain Physician 2009; 12:437-460.
32. Manchikanti L, Singh V, Falco FJ, Cash KA, Fellows B. Cervical medial branch blocks for chronic cervical facet joint pain: A randomized double-blind, controlled trial with one-year follow-up. Spine (Phila Pa 1976) 2008; 33:1813-1820.
33. Manchikanti L, Cash KA, McManus CD, Pampati V, Smith HS. One year results of a randomized, double-blind, active controlled trial of fluoroscopic caudal epidural injections with or without steroids in managing chronic discogenic low back pain without disc herniation or radiculitis. Pain Physician 2011; 14:25-36.
34. Manchikanti L, Singh V, Cash KA, Pampati V, Damron KS, Boswell MV. Preliminary results of randomized, equivalence trial of fluoroscopic caudal epidural injections in managing chronic low back pain: Part 2. Disc herniation and radiculitis. Pain Physician 2008; 11:801-815.
35. Manchikanti L, Cash RA, McManus CD, Pampati V, Fellows B. Fluoroscopic caudal epidural injections with or without steroids in managing pain of lumbar spinal stenosis: One year results of randomized, double-blind, activecontrolled trial. J Spinal Disord 2011; in press.
36. Manchikanti L, Singh V, Cash KA, Pampati V, Datta S. Management of pain of post lumbar surgery syndrome: Oneyear results of a randomized, double double-blind, active controlled trial of fluoroscopic caudal epidural injections. Pain Physician 2010; 13:509-521.
37. Manchikanti L, Pampati V, Boswell MV, Smith HS, Hirsch JA. Analysis of the growth of epidural injections and costs in the Medicare population: A comparative evaluation of 1997, 2002, and 2006 data. Pain Physician 2010; 13:199-212.
38. Manchikanti L, Cash KA, McManus CD, Pampati V, Singh V, Benyamin RM. The preliminary results of a comparative effectiveness evaluation of adhesiolysis and caudal epidural injections in managing chronic low back pain secondary to spinal stenosis: A randomized, equivalence controlled trial. Pain Physician 2009; 12:E341-E354.
39. Manchikanti L, Singh V, Cash KA, Pampati V, Datta S. A comparative effectiveness evaluation of percutaneous adhesiolysis and epidural steroid injections in managing lumbar post surgery syndrome: A randomized, equivalence controlled trial. Pain Physician 2009; 12:E355-E368.
40. Manchikanti L, Pampati V, Cash KA. Protocol for evaluation of the comparative effectiveness of percutaneous adhesiolysis and caudal epidural steroid injections in low back and/or lower extremity pain without post surgery syndrome or spinal stenosis. Pain Physician 2010; 13:E91-E110.
41. Epter RS, Helm S, Hayek SM, Benyamin RM, Smith HS, Abdi S. Systematic review of percutaneous adhesiolysis and management of chronic low back pain in post lumbar surgery syndrome. Pain Physician 2009; 12:361-378.
42. Singh V, Manchikanti L, Benyamin RM, Helm S, Hirsch JA. Percutaneous lumbar laser disc decompression: A systematic review of current evidence. Pain Physician 2009; 12:573-588.
43. Singh V, Benyamin RM, Datta S, Falco FJE, Helm S, Manchikanti L. Systematic review of percutaneous lumbar mechanical disc decompression utilizing Dekompressor. Pain Physician 2009; 12:589-599.
44. Manchikanti L, Derby R, Benyamin RM, Helm S, Hirsch JA. A systematic review of mechanical lumbar disc decompression with nucleoplasty. Pain Physician 2009; 12:561-572.
45. Hirsch JA, Singh V, Falco FJE, Benyamin RM, Manchikanti L. Automated percutaneous lumbar discectomy for the contained herniated lumbar disc: A systematic assessment of evidence. Pain Physician 2009; 12:601-620.
46. Gerges FJ, Lipsitz SR, Nedeljkovic SS. A systematic review on the effectiveness of the nucleoplasty procedure for discogenic pain. Pain Physician 2010; 13:117-132.
47. Frey ME, Manchikanti L, Benyamin RM, Schultz DM, Smith HS, Cohen SP. Spinal cord stimulation for patients with failed back surgery syndrome: A systematic review. Pain Physician 2009; 12:379-397.
48. Benyamin RM, Datta S, Falco FJE. A perfect storm in interventional pain management: Regulated, but unbalanced. Pain Physician 2010; 13:109-116.
49. Manchikanti L, Singh V, Boswell MV. Interventional pain management at crossroads: The perfect storm brewing for a new decade of challenges. Pain Physician 2010; 13:E111-E140.
50. Helm S, Hayek S, Benyamin RM, Manchikanti L. Systematic review of the effectiveness of thermal annular procedures in treating discogenic low back pain. Pain Physician 2009; 12:207-232.
51. Patel VB, Manchikanti L, Singh V, Schultz DM, Hayek SM, Smith HS. Systematic review of intrathecal infusion systems for long-term management of chronic non-cancer pain. Pain Physician 2009; 12:345-360.
52. Rupert MP, Lee M, Manchikanti L, Datta S, Cohen SP. Evaluation of sacroiliac joint interventions: A systematic appraisal of the literature. Pain Physician 2009; 12:399-418.
53. Manchikanti L, Singh V, Falco FJE, Cash KA, Fellows B. Comparative outcomes of a 2-year follow-up of cervical medial branch blocks in management of chronic neck pain: A randomized, double-blind controlled trial. Pain Physician 2010; 13:437-450.
54. Manchikanti L, Singh V, Falco FJE, Cash KA, Pampati V, Fellows B. Comparative effectiveness of a one-year follow-up of thoracic medial branch blocks in management of chronic thoracic pain: A randomized, double-blind active controlled trial. Pain Physician 2010; 13:535-548.
55. Manchikanti L, Cash KA, Pampati V, Wargo BW, Malla Y. Cervical epidural injections in chronic discogenic neck pain without disc herniation or radiculitis: Preliminary results of a randomized, double-blind, controlled trial. Pain Physician 2010; 13:E265-E278.
56. Manchikanti L, Cash KA, Pampati V, Wargo BW, Malla Y. The effectiveness of fluoroscopic cervical interlaminar epidural injections in managing chronic cervical disc herniation and radiculitis: Preliminary results of a randomized, double-blind, controlled trial. Pain Physician 2010; 13:223-236.
57. Manchikanti L, Singh V, Falco FJE, Cash KA, Pampati V. Evaluation of the effectiveness of lumbar interlaminar epidural injections in managing chronic pain of lumbar disc herniation or radiculitis: A randomized, double-blind, controlled trial. Pain Physician 2010; 13:343-355.
58. Manchikanti L, Cash KA, McManus CD, Pampati V, Benyamin RM. Preliminary results of a randomized, double-blind, controlled trial of fluoroscopic lumbar interlaminar epidural injections in managing chronic lumbar discogenic pain without disc herniation or radiculitis. Pain Physician 2010; 13:E279-E292.
59. Manchikanti L, Cash KA, McManus CD, Pampati V, Benyamin RM. A preliminary report of a randomized double-blind, active controlled trial of fluoroscopic thoracic interlaminar epidural injections in managing chronic thoracic pain. Pain Physician 2010; 13:E357-E369.
60. Manchikanti L, Datta S, Derby R, Wolfer LR, Benyamin RM, Hirsch JA. A critical review of the American Pain Society clinical practice guidelines for interventional techniques: Part 1. Diagnostic interventions. Pain Physician 2010; 13:E141-E174.
61. Manchikanti L, Datta S, Gupta S, Munglani R, Bryce DA, Ward SP, Benyamin RM, Sharma ML, Helm II S, Fellows B, Hirsch JA. A critical review of the American Pain Society clinical practice guidelines for interventional techniques: Part 2. Therapeutic interventions. Pain Physician 2010; 13:E215-E264.
62. Manchikanti L, Singh V, Falco FJE, Cash KA, Pampati V. Evaluation of lumbar facet joint nerve blocks in managing chronic low back pain: A randomized, doubleblind, controlled trial with a 2-year follow-up. Int J Med Sci 2010; 7:124-135.
63. Papachristou DJ, Basdra EK, Papavassiliou AG. Bone metastases: Molecular mechanisms and novel therapeutic interventions. Med Res Rev 2010 Sept 3 [Epub ahead of print].
64. Santini D, Galluzzo S, Zoccoli A, Pantano F, Fratto ME, Vincenzi B, Lombardi L, Gucciardino C, Silvestris N, Riva E, Rizzo S, Russo A, Maiello E, Colucci G, Tonini G. New molecular targets in bone metastases. Cancer Treat Rev 2010; 36:S6-S10.
65. Jung Y, Wang J, Schneider A, Sun YX, Koh-Paige AJ, Osman NI, McCauley LK, Taichman RS. Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone 2006; 38:497-508.
66. Koutsilieris M. Osteoblastic metastasis in advanced prostate cancer. Anticancer Research 1993; 13:443-449.
67. Koutsilieris M. Skeletal metastases in advanced prostate cancer: cell biology and therapy. CritRev Oncol Hematol1995; 18:51-64.
68. Msaouel P, Pissimissis N, Halapas A, Koutsilieris M. Mechanisms of bone metastasis in prostate cancer: Clinical implications. Best Pract Res Clin Endocrinol Metab 2008; 22:341-355.
69. Hsu H, Lacey DL, Dunstan CR, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 1999; 96:3540-3545.
70. Mori K, Le Goff B, Charrier C, Battaglia S, Heymann D, Rédini F. DU145 human prostate cancer cells express functional receptor activator of NFkappaB: New insights in the prostate cancer bone metastasis process. Bone 2007; 40:981-990.
71. Koutsilieris M, Frenette G, Lazure C, Lehoux JG, Govindan MV, Polychronakos C. Urokinase-type plasminogen activator: a paracrine factor regulating the bioavailability of IGFs in PA-III cell-induced osteoblastic metastases. Anticancer Res 1993; 13:481-486.
72. Reyes-Moreno C, Frenette G, Boulanger J, Lavergne E, Govindan MV, Koutsilieris M. Mediation of glucocorticoid receptor function by transforming growth factor beta I expression in human PC-3 prostate cancer cells. Prostate 1995; 26:260-269.
73. Koutsilieris M, Tenta R, Tiblalexi D, Pitulis N, Sotiriou E, Lembessis P, Bogdanos J, Milathianakis, Sourla A. Bone metastasis microenvironment participates in the development of androgen ablation refractoriness and chemotherapy resistance of prostate cancer cells residing in the skeleton: clinical implications. In: Meadows G (ed). Integration/Interaction of Oncologic Growth. Springer, Netherlands, 2005, pp 335-344.
74. Koutsilieris M, Reyes-Moreno C, Sourla A, Dimitriadou V, Choki I. Growth factors mediate glucocorticoid receptor function and dexamethasone-induced regression of osteoblastic lesions in hormone refractory prostate cancer. Anticancer Res 1997; 17:1461-1465.
75. Koutsilieris M, Dimopoulos T, Milathianakis C, Bogdanos J, Karamanolakis D, Pissimissis N, Halapas A, Lembessis P, Papaioannou A, Sourla A. Combination of somatostatin analogues and dexamethasone (anti-survival-factor concept) with luteinizing hormone-releasing hormone in androgen ablation-refractory prostate cancer with bone metastasis. BJU Int 2007; 100:60-62.
76. Smith HS. Novel analgesic approaches to painful bone metastases. In: Smith, HS (ed). Drugs for Pain. Hanley and Belfus, Philadelphia, 2003, pp 489-497.
77. Galasko CSB. Mechanisms of lytic and blastic metastatic disease of bone. Clin Orthop 1982; 169:20-27.
78. Murphy MG, Cerchio K, Stoch SA, Gottesdiener K, Wu M, Recker R; L-000845704 Study Group. Effect of L-000845704, an aVb3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 2005; 90:2022-2028.
79. Granot-Attas S, Luxenburg C, Finkelshtein E, Elson A. Protein tyrosine phosphatase epsilon regulates integrin-mediated podosome stability in osteoclasts by activating Src. Mol Biol Cell 2009; 20:4324-4334.
80. Sly WS, Hewett-Emmett D, Whyte MP, Yu YS, Tashian RE. Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci USA 1983; 80:2752-2756.
81. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med 2004; 351:2839-2849.
82. Jansen I, De Vries T, Ravesloot J, Everts V, Oude Elferink R. Loss of anion exchanger 2 (Ae2) in mice results in osteopetrosis. J Bone Miner Res 2006; 21:1256.
83. Teti A, Blair HC, Teitelbaum SL, Kahn AJ, Koziol C, Konsek J, Zambonin-Zallone A, Schlesinger PH. Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts. J Clin Invest 1989; 83:227-233.
84. Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson AK, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet 2000; 25:343-346.
85. Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch TJ, Kubisch C. Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet 2000; 9:2059-2063.
86. Li YP, Chen W, Liang Y, Li E, Stashenko P. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclastmediated extracellular acidification. Nat Genet 1999; 23:447-451.
87. Scimeca JC, Franchi A, Trojani C, Parrinello H, Grosgeorge J, Robert C, Jaillon O, Poirier C, Gaudray P, Carle GF. The gene encoding the mouse homologue of the human osteoclast-specific 116-kDa V-ATPase subunit bears a deletion in osteosclerotic (oc/oc) mutants. Bone 2000; 26:207-213.
88. Blair HC, Teitelbaum SL, Ghiselli R, Gluck S. Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 1989; 245:855-857.
89. Blair HC, Teitelbaum SL, Tan HL, Koziol CM, Schlesinger PH. Passive chloride permeability charge coupled to H(+)-ATPase of avian osteoclast ruffled membrane. Am J Physiol 1991; 260:C1315-C1324.
90. Henriksen K, Gram J, Schaller S, Dahl BH, Dziegiel MH, Bollerslev J, Karsdal MA. Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am J Pathol 2004; 164:1537-1545.
91. Karsdal MA, Henriksen K, Sørensen MG, Gram J, Schaller S, Dziegiel MH, Heegaard AM, Christophersen P, Martin TJ, Christiansen C, Bollerslev J. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am J Pathol 2005; 166:467-476.
92. Kornak U, Kasper D, Bosl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch TJ. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 2001; 104:205-215.
93. Baron R, Neff L, Louvard D, Courtoy PJ. Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border. J Cell Biol 1985; 101:2210-2222.
94. Miyazaki T, Neff L, Tanaka S, Horne WC, Baron R. Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol 2003; 160:709-718.
95. Miyazaki T, Sanjay A, Neff L, Tanaka S, Horne WC, Baron R. Src kinase activity is essential for osteoclast function. J Biol Chem 2004; 279:17660-17666.
96. Miyazaki T, Tanaka S, Sanjay A, Baron R. The role of c-Src kinase in the regulation of osteoclast function. Mod Rheumatol 2006; 16:68-74.
97. Bossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR, Jones C, Kurdyla JT, McNulty DE, Drake FH, Gowen M, Levy MA. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem 1996; 271:12517-12524.
98. Gowen M, Lazner F, Dodds R, Kapadia R, Feild J, Tavaria M, Bertoncello I, Drake F, Zavarselk S, Tellis I, Hertzog P, Debouck C, Kola I. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 1999; 14:1654-1663.
99. Nishi Y, Atley L, Eyre DE, Edelson JG, Superti-Furga A, Yasuda T, Desnick RJ, Gelb BD. Determination of bone markers in pycnodysostosis: eVects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res 1999; 14:1902-1908.
100. Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, Moritz JD, Schu P, von Figura K. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci USA 1998; 95:13453-13458.
101. Everts V, Delaisse JM, Korper W, Jansen DC, Tigchelaar-Gutter W, Saftig P, Beertsen W. The bone lining cell: Its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res 2002; 17:77-90.
102. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004; 350:1655-1664.
103. Kawatani M, Osada H. Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases. Cancer Sci 2009; 100:1999-2005.
104. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002; 2:584-593.
105. Clines GA, Guise TA. Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med 2008; 10:E7.
106. Sterling JA, Oyajobi BO, Grubbs B, Padalecki SS, Munoz SA, Gupta A, Story B, Zhao M, Mundy GR. The hedgehog signaling molecule Gli2 induces parathyroid hormone-related peptide expression and osteolysis in metastatic human breast cancer cells. Cancer Res 2006; 66:7548-7553.
107. Pratap J, Wixted JJ, Gaur T, Zaidi SK, Dobson J, Gokul KD, Hussain S, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Runx2 transcriptional activation of Indian hedgehog and a downstream bone metastatic pathway in breast cancer cells. Cancer Res 2008; 68:7795-7802.
108. Pratap J, Javed A, Languino LR, van Wijnen AJ, Stein JL, Stein GS, Lian JB. The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion. Mol Cell Biol 2005; 25:8581-8591.
109. Akech J, Wixted JJ, Bedard K, van der Deen M, Hussain S, Guise TA, van Wijnen AJ, Stein JL, Languino LR, Altieri DC, Pratap J, Keller E, Stein GS, Lian JB. Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. Oncogene 2010; 29:811-821.
110. Pratap J, Lian JB, Stein GS. Metastatic bone disease: role of transcription factors and future targets. Bone 2011; 48:30-36.
111. Bruera E, Kim HN. Cancer pain. JAMA 2003; 290:2476-2479.
112. Hanks GW. The pharmacological treatment of bone pain. Cancer Surv 1988; 7:87-101.
113. Burton AW, Cleeland CS. Cancer pain: progress since the WHO guidelines. Pain Pract 2001; 1:236-242.
114. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: A 10-year prospective study. Pain 1995; 63:65-76.
115. Minotti V, de Angelis V, Righetti E, Celani MG, Rossetti R, Lupatelli M, Tonato M, Pisati R, Monza G, Fumi G, Del Favero A. Double-blind evaluation of shortterm analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain. Pain 1998; 74:133-137.
116. Minotti V, Patoia L, Roila F, Basurto C, Tonato M, Pasqualucci V, Maresca V, Del Favero A. Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain. Pain 1989; 36:177-183.
117. Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997; 99:2254-2259.
118. Sumitani K, Kamijo R, Toyoshima T, Nakanishi Y, Takizawa K, Hatori M, Nagumo M. Specific inhibition of cyclooxygenase results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production. J Oral Pathol Med 2001; 30:41-47.
119. Sabino MAC, Ghilardi JR, Jongen JLM, Keyser CP, Luger NM, Mach DB, Peters CM, Rogers SD, Schwei MJ, de Felipe C, Mantyh PW. Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res 2002; 62:7343-7349.
120. Manchikanti L, Fellows B, Ailinani H, Pampati V. Therapeutic use, abuse, and nonmedical use of opioids: A ten-year perspective. Pain Physician 2010; 13:401-435.
121. Donovan-Rodriguez T, Dickenson AH, Urch CE. Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancerinduced bone pain. Anesthesiology 2005; 102:132-140.
122. Honore, P, Mantyh, PW. Bone cancer pain: from mechanism to model to therapy. Pain Med 2000; 1:303-309.
123. Caraceni, A, Zecca, E, Bonezzi, C, Arcuri, E, Yaya Tur, R, Maltoni, M, Visentin M, Gorni G, Martini C, Tirelli W, Barbieri M, De Conno F. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol 2004; 22:2909-2917.
124. Caraceni A, Zecca E, Martini C, Pigni A, Bracchi P. Gabapentin for breakthrough pain due to bone metastases. Palliat Med 2008; 22:392-393.
125. Viereck V, Emons G, Lauck V, Frosch KH, Blaschke S, Gründker C, Hofbauer LC. Bisphosphonates pamidronate and zeoldronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun 2002; 291:680-686.
126. Costa L, Major PP. Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Pract Oncol 2009; 6:163-174.
127. Green JR: Bisphosphonates: preclinical review. Oncologist 2004; 9:3-13.
128. Mönkkönen H, Auriola S, Lehenkari P, Kellinsalmi M, Hassinen IE, Vepsäläinen J, Mönkkönen J. A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. Br J Pharmacol 2006; 147:437-445.
129. Finley RS. Bisphosphonates in the treatment of bone metastases. Semin Onco 2002; 129:32-138.
130. Berenson JR, Hillner BE, Kyle RA, Anderson K, Lipton A, Yee GC, Biermann JS; American Society of Clinical Oncology Bisphosphonates Expert Panel. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 2002; 20:3719-3736.
131. Pistevou-Gombaki K. Eleftheriadis N, Sofroniadis I, Makris P, Kouloulias V. Palliative treatment of painful bone metastases from non-Hodgkin lympoma with disodium pamidronate. J Exp Clin Cancer Res 2002; 21:429-432.
132. Santini D, Fratto ME, Vincenzi B, Galluzzo S, Tonini G. Zoledronic acid in the management of metastatic bone disease. Expert Opin Biol Ther 2006; 6:1333-1348.
133. Clemons MJ, Dranitsaris G, Ooi WS, Yogendran G, Sukovic T, Wong BY, Verma S, Pritchard KI, Trudeau M, Cole DE. Phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal-related event or progressive bone metastases despite first-line bisphosphonate therapy. J Clin Oncol 2006; 24:4895-4900.
134. Amir E, Whyne C, Freedman OC, Fralick M, Kumar R, Hardisty M, Clemons M. Radiological changes following secondline zoledronic acid treatment in breast cancer patients with bone metastases. Clin Exp Metastasis 2009; 26:479-484.
135. Furlow B. Zoledronic acid palliation in bone-metastatic breast cancer. Lancet Oncol 2006; 7:894.
136. Fulfaro F, Leto G, Badalamenti G, Arcara C, Cicero G, Valerio MR, Di Fede G, Russo A, Vitale A, Rini GB, Casuccio A, Intrivici C, Gebbia N. The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers. J Chemother 2005; 17:555-559.
137. Rachner TD, Singh SK, Schoppet M, Benad P, Bornhäuser M, Ellenrieder V, Ebert R, Jakob F, Hofbauer LC. Zoledronic acid induces apoptosis and changes the trail/opg ratio in breast cancer cells. Cancer Lett 2010; 287:109-116.
138. Woodward JK, Neville-Webbe HL, Coleman RE, Holen I. Combined effects of zoledronic acid and doxorubicin on breast cancer cell invasion in vitro. Anticancer Drugs 2005; 16:845-854.
139. Hiraga T, Williams PJ, Ueda A, Tamura D, Yoneda T. Zoledronic acid inhibits visceral metastases in the 4t1/luc mouse breast cancer model. Clin Cancer Res 2004; 10:4559-4567.
140. Santini D, Vincenzi B, Galluzzo S, Battistoni F, Rocci L, Venditti O, Schiavon G, Angeletti S, Uzzalli F, Caraglia M, Dicuonzo G, Tonini G. Repeated intermittent low-dose therapy with zoledronic acid induces an early, sustained, and long-lasting decrease of peripheral vascular endothelial growth factor levels in cancer patients. Clin Cancer Res 2007; 13:4482-4486.
141. Vincenzi B, Santini D, Dicuonzo G, Battistoni F, Gavasci M, La Cesa A, Grilli C, Virzì V, Gasparro S, Rocci L, Tonini G. Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 2005; 25:144-151.
142. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B; Zoledronic Acid Prostate Cancer Study Group. A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94:1458-1468.
143. Rosen LS, Gordon D, Tchekmedyian S, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, de Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman JJ. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase II, double-blind, randomized trial-The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003; 21:3150-3157.
144. Rosen LS, Gordon DH, Dugan W Jr, Major P, Eisenberg PD, Provencher L, Kaminski M, Simeone J, Seaman J, Chen BL, Coleman RE. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004; 100:36-43.
145. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg 2004; 62:527-534.
146. Kreeger L, Hutton-Potts J. The use of calcitonin in the treatment of metastatic bone pain. J Pain Sumptom Manage 1999; 17:2-5.
147. Mystakidou K, Befon S, Hondros K, Kouskouni E, Vlahos L. Continuous subcutaneous administration of high-dose salmon calcitonin in bone metastasis: pain control and beta-endorphin plasma levels. J Pain Symptom Manage 1999; 18:323-330.
148. Tsavaris N, Kopterides P, Kosmas C, Vadiaka M, Dimitrakopoulos A, Scopelitis H, Tenta R, Vaiopoulos G, Koufos C. Analgesic activity of high-dose intravenous calcitonin in cancer patients with bone metastases. Oncol Rep 2006; 16:871-875.
149. Martinez MJ, Roqué M, Alonso-Coello P, Català E, Garcia JL, Ferrandiz M. Calcitonin for metastatic bone pain. Cochrane Database Syst Rev 2003; (3):CD003223.
150. Martinez-Zapata MJ, Roqué M, Alonso-Coello P, Català E. Calcitonin for metastatic bone pain. Cochrane Database Syst Rev 2006; 3:CD003223.
151. Molina A, Belldegrun A. Novel therapeutic strategies for castration resistant prostate cancer: Inhibition of persistent androgen production and androgen receptor mediated signaling. J Urol 2001; 185:787-794.
152. Sharifi N, Gulley JL, Dahut WL. An update on androgen deprivation therapy for prostate cancer. Endocr Relat Cancer 2010: 17:R305-R315.
153. Perlmutter MA, Lepor H. Androgen deprivation therapy in the treatment of advanced prostate cancer. Rev Urol 2007; 9:S3-S8.
154. Heidenreich H, Aus G, Bolla M, Joniau S, Mayveev VB, Schmid HP, Zattoni F, European Association of Urology. EAU guidelines on prostate cancer. Eur Urol 2008; 53:68-80.
155. Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Schmid HP, Van der Kwast T, Wiegel T, Zattoni F, Heidenreich A. EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer. Eur Urol 2011; 59:572-583.
156. Van Poppel H. Evaluation of degarelix in the management of prostate cancer. Cancer Manag Res 2010; 2:39-52.
157. Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: A phase 1-2 study. Lancet 2010; 375:1437-1446.
158. Zivi A, Massard C, De-Bono J. Changing therapeutic paradigms in castrateresistant prostate cancer. Clin Genitourin Cancer 2010; 8:17-22.
159. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radat Oncol Biol Phys 1991; 21:109-122.
160. Smith HS. Radiation-induced analgesia in painful osseous metastases. In: Proceedings at at the Capital District Pain Conference. Albany, NY, October 2005.
161. Lin A, Ray ME. Targeted and systemic radiotherapy in the treatment of bone metastasis. Cancer Metastases Rev 2006; 25:669-675.
162. Tong D, Gillick L, Hendrickson FR. The palliation of symptomatic osseous metastases: Final results of the study by the Radiation Therapy Oncology Group. Cancer 1982; 50:893-899.
163. Arcangeli G, Micheli A, Arcangeli G, Giannarelli D, La Pasta O, Tollis A, Vitullo A, Ghera S, Benassi M. The responsiveness of bone metastases to radiotherapy: the effect of site, histology and radiation dose on pain relief. Radiother Oncol 1989; 14:95-101.
164. Poulter CA, Cosmatos D, Rubin P, Urtasun R, Cooper JS, Kuske RR, Hornback N, Coughlin C, Weigensberg I, Rotman M. A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases. Int J Radiat Oncol Biol Phys 1992; 23:207-214.
165. Jeremic B. Single fraction external beam radiation therapy in the treatment of localized metastatic bone pain. A review. J Pain Symptom Manage 2001; 22:1048-1058.
166. Wu JS, Wong R, Johnston M, Bezjak A, Whelan T; Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group. Meta-analysis of dose fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 2003; 55:594-605.
167. Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain: Single fraction versus multifraction radiotherapy--A systematic review of randomized trials. Clin Oncol (R Coll Radiol) 2003; 15:345-352.
168. Chow E, Harris K, Fan G, Tsao MN, Sze WM. Palliative radiotherapy trials for bone metastases: A systematic review. J Clin Oncol 2007; 25:1423-1436.
169. Rades D, Schild SE, Abrahm JL. Treatment of painful bone metastases. Nat Rev Clin Oncol 2010; 7:220-229.
170. Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med 2010; 40:89-104.
171. Robinson RG, Blake GM, Preston DF, McEwan AJ, Spicer JA, Martin NL, Wegst AV, Ackery DM. Strontium-89: Treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone. Radiographics 1989; 9:271-281.
172. Robinson RG, Preston DF, Spicer JA. Radionuclide therapy of intractable bone pain: Emphasis on strontium-89. Semin Nucl Med 1992; 22:28-32.
173. Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med 1985; 26:345-348.
174. Kraeber-Bodéré F, Campion L, Rousseau C, Bourdin S, Chatal JF, Resche I. Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement. Eur J Nucl Med 2000; 27:1487-1493.
175. Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: A systematic review. Lancet Oncol 2005; 6:392-400.
176. Friedell HL, Storaasli JP. The use of radioactive phosphorus in the treatment of carcinoma of the breast with widespread metastases to bone. Am J Roentgenol Radium Ther Nucl Med 1950; 64:559-575.
177. Silberstein EB. The treatment of painful osseous metastases with phosphorus-32-labeled phosphates. Semin Oncol 1993; 20:10-21.
178. Samarium-153-lexidronam. Clinical Pharmacology. www.clinicalpharmacology.com/?epm=2_1.
179. Samarium-153-lexidronam for painful bone metastases. Med Lett Drugs Ther 1997; 39:83-84.
180. Holmes RA. [153Sm] EDTMP: A potential therapy for bone cancer pain. Semin Nucl Med 1992; 22:41-45.
181. Bayouth JE, Macey DJ, Kasi LP, Fossella FV. Dosimetry and toxicity of samarium-153EDTMP administered for bone pain due to skeletal metastases. J Nucl Med 1994; 35:63-69.
182. Collins C, Eary JF, Donaldson G, Vernon C, Bush NE, Petersdorf S, Livingston RB, Gordon EE, Chapman CR, Appelbaum FR. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: A phase I/II trial. J Nucl Med 1993; 34:1839-1844.
183. Alberts AS, Smit BJ, Louw WK, van Rensburg AJ, van Beek A, Kritzinger V, Nel JS. Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone. Radioth Oncol 1997; 43:175-179.
184. Sartor O, Reid RH, Bushnell DL, Quick DP, Ell PJ. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer 2007; 109:637-643.
185. Kavakli K, Aydogdu S, Taner M, Duman Y, Balkan C, Karapinar DY, Saydam G, Capaci K, Oktay A. Radioisotope synovectomy with rhenium186 in haemophilic synovitis for elbows, ankles and shoulders. Haemophilia 2008; 14:518-523.
186. Bucerius J, Wallny T, Brackmann HH, Joe AY, Roedel R, Biersack HJ, Palmedo H. Rhenium-186 hydroxyethylidenediphosphonate (186Re HEDP) for the treatment of hemophilic arthropathy: First results. Clin J Pain 2007; 23:612-618.
187. Bodei L, Lam M, Chiesa C, Flux G, Brans B, Chiti A, Giammarile FL; European Association of Nuclear Medicine (EANM). EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Mucl Med Mol Imaging 2008; 35:1934-1940.
188. Maxon HR 3rd, Schroder LE, Hertzberg VS, Thomas SR, Englaro EE, Samaratunga R, Smith H, Moulton JS, Moulton JS, Williams CC, Ehrhardt GJ, Schenider HJ. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med 1991; 32:1877-1881.
189. Han SH, de Klerk JM, Tan S, van het Schip AD, Derksen BH, van Dijk A, Kruitwagen CL, Blijham GH, van Rijk PP, Zonnenberg BA. The PLACORHEN study: A double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormoneresistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study. J Nucl Med 2002; 43:1150-1156.
190. Sciuto R, Tofani A, Festa A, Giannarelli D, Pasqualoni R, Maini CL. Short-and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases. J Nucl Med 2000; 41:647-654.
191. Sciuto R, Festa A, Pasqualoni R, Semprebene A, Rea S, Bergomi S, Maini CL. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Breast Cancer Res Treat 2001; 66:101-109.
192. Lambert B, de Klerk JM. Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. Nucl Med Commun 2006; 27:223-239.
193. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer 2003; 89:625-629.
194. Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Risse J, Grünwald F, Knapp FF Jr, Biersack HJ. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med 2000; 27:123-130.
195. Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, Joe A, Roedel R, Fimmers R, Knapp FF Jr, Guhlke S, Biersack HJ. J Clin Oncol 2003; 21:2869-2875.
196. Liepe K. Alpharadin, a 223Ra-based alpha-particle-emitting pharmaceutical for the treatment of bone metastases in patients with cancer. Curr Opin Investig Drugs 2009; 10:1346-1358.
197. Callstrom MR, Charboneau JW. Imageguided palliation of painful metastases using percutaneous ablation. Tech Vasc Interv Radiol 2007; 10:120-131.
198. Dupuy DE, Hong R, Oliver B, Goldberg SN. Radiofrequency ablation of spinal tumors: temperature distribution in the spinal canal. AJR AM J Roentgenal 2000; 175:1263-1266.
199. Dodd GD, 3rd, Frank MS, Aribandi M, Chopra S, Chintapalli KN. Radiofrequency thermal ablation: Computer analysis of the size of the thermal injury created by overlapping ablations. AJR AM J Roentgenal 2001; 177:777-782.
200. Tancioni F, Lorenzetti MA, Navarria P, Pessina F, Draghi R, Pedrazzoli P, Scorsetti M, Alloisio M, Santoro A, Rodriguezy Baena R. Percutaneous vertebral augmentation in metastatic disease: state of the art. J Support Oncol 2011; 9:4-10.
201. Peh WC, Gilula LA. Percutaneous vertebroplasty: indications, contraindications, and technique. Br J Radiol 2003; 76:69-75.
202. Peh WCG, Gilula LA, Peck DD. Percutaneous vertebroplasty for severe osteoporotic vertebral body compression fractures. Radiology 2002; 223:121-126.
203. Kassamali RH, Ganeshan A, Hoey ET, Crowe PM, Douis H, Henderson J. Pain management in spinal metastases: The role of percutaneous vertebral augmentation. Ann Oncol 2010; 22:782-786.
204. Lee B, Franklin I, Lewis JS, Coombes RC, Leonard R, Gishen P, Stebbing J. The efficacy of percutaneous vertebroplasty for vertebral metastases associated with solid malignancies. Eur J Cancer 2009; 45:1597-1602.
205. Saliou G, Kocheida el M, Lehmann P, Depriester C, Paradot G, Le Gars D, Balut A, Deramond H. Percutaneous vertebroplasty for pain management in malignant fractures of the spine with epidural involvement. Radiology 2010; 254:882-890.
206. Mikami Y, Numaguchi Y, Kobayashi N, Fuwa S, Hoshikawa Y, Saida Y. Therapeutic effects of percutaneous vertebroplasty for vertebral metastases. Jpn J Radiol 2001; 29:202-206.
207. Chew C, Craig L, Edwards R, Moss J, O'Dwyer PJ. Safety and efficacy of percutaneous vertebroplasty in malignancy: A systematic review. Clin Radiol 2011; 66:63-72.
208. Qian Z, Sun Z, Yang H, Gu Y, Chen K, Wu G. Kyphoplasty for the treatment of malignant vertebral compression fractures caused by metastases. J Clin Neurosci 2011; 18:763-767.
209. Watanabe A, Yamakage M. Intrathecal neurolytic block in a patient with refractory cancer pain. J Anesth 2011; [Epub ahead of print].
210. Wilkes D, Cook M, Solanki D. Intrathecal catheter-syringe adaptor for shortterm intrathecal analgesia with an externalized pump: A case report. Pain Physician 2010; 13:151-156.
211. Deer TR, Kim C, Bowman R, Tolentino D, Stewart C, Tolentino W. Intrathecal ziconotide and opioid combination therapy for noncancer pain: An observational study. Pain Physician 2009; 12:E291-E296.
212. El-Sheikh N, Boswell MV. Plasma Betaendorphin levels before and after relief of cancer pain. Pain Physician 2004; 7:67-70.
213. Raffaeli W, Sarti D, Demartini L, Sotgiu A, Bonezzi C; Italian Ziconotide Group. Italian registry on long-term intrathecal ziconotide treatment. Pain Physician 2011; 14:15-24.
214. Frey ME. Redo kyphoplasty with vertebroplasty techniques. A case report and review of the literature. Pain Physician 2009; 12:645-649.
215. Betts A. Vertebroplasty of the first sacral vertebra. Pain Physician 2009; 12:651-657.
216. Gill JB, Kuper M, Chin PC, Zhang Y, Schutt R Jr. Comparing pain reduction following kyphoplasty and vertebroplasty for osteoporotic vertebral compression fractures. Pain Physician 2007; 10:583-590.
217. Manchikanti L, Falco FJE, Boswell MV, Hirsch JA. Facts, fallacies, and politics of comparative effectiveness research: Part 1. Basic considerations. Pain Physician 2010; 13:E23-E54.
218. Manchikanti L, Falco FJE, Boswell MV, Hirsch JA. Facts, fallacies, and politics of comparative effectiveness research: Part 2. Implications for interventional pain management. Pain Physician 2010; 13:E55-E79.
219. Newsome S, Frawley BK, Argoff CE. Intrathecal analgesia for refractory cancer pain. Curr Pain Headache Rep 2008; 12:249-256.
220. Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H. Intrathecal drug delivery. Pain Physician 2008; 11:S89-S104.
221. Smith TJ, Staats PS, Deer T, Sterns, LJ, Rauck RL, Boortz-Marx RL, Buchser E, Català E, Bryce DA, Coyne PJ, Pool GE; Implantable Drug Delivery Systems Study Group. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 2002; 20:4040-4049.
222. Deer T, Krames ES, Hassenbusch SJ, Burton A, Caraway D, Dupen S, Eisenach J, Erdek M, Grigsby E, Kim P, Levy R, McDowell G, Mekhail N, Panchal S, Prager J, Rauck R, Saulino M, Sitzman T, Staats P, Stanton-Hicks M, Stearns L, Willis KD, Witt W, Follett K, Huntoon M, Liem L, Rathmell J, Wallace M, Buchser E, Cousins M, Ver Donck A. Polyanalgesic Consensus Conference 2007: Recommendations for the management of pain by intrathecal (intraspinal) drug delivery: Report of an interdisciplinary expert panel. Neuromodulation: Technol Neural Interface 2007; 10:300-328.
223. Hawley P, Beddard-Huber E, Grose C, McDonald W, Lobb D, Malysh L. Intrathecal infusions for intractable cancer pain: a qualitative study of the impact on a case series of patients and caregivers. Pain Res Manag 2009; 14:371-379.
224. Furuse S, Kawamata T, Yamamoto J, Niiyama Y, Omote K, Watanabe M, Namiki A. Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain. Anesthesiology 2009; 111:173-186.
225. Gu X, Mei F, Liu Y, Zhang R, Zhang J, Ma Z. Intrathecal Administration of the Cannabinoid 2 Receptor Agonist JWH015 Can Attenuate Cancer Pain and Decrease mRNA Expression of the 2B Subunit of N-Methyl-D-Aspartic Acid. Anesth Analg 2011; In Press.
226. Cui JH, Kim WM, Lee HG, Kim YO, Kim CM, Yoon MH. Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model. Neurosci Lett 2011; 493:67-71.
227. Yoon MH, Kim WM, Lee HG, Choi JI, Kim YO, Song JA. Analgesic effect of intrathecal ginsenosides in a murine bone cancer pain. Korean J Pain 2010; 23:230-235.
228. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch ER, Van G, Nguyen LT, Ohashi PS, Lacey DL, Fish E, Boyle WJ, Penninger JM. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin legand. Nature 1999; 402:304-308.
229. Simonet WS, Lacey DL, Dunstan CR, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 1997; 89:309-319.
230. Thompson SWN, Tonge D. Bone cancer gain without the pain. Nat Med 2000; 6:504-505.
231. Body JJ, Greipp P, Coleman RE, Facon T, Geurs F, Fermand JP, Harousseau JL, Lipton A, Mariette X, Williams CD, Nakanishi A, Holloway D, Martin SW, Dunstan CR, Bekker PJ. A Phase I study of amgn-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 2003; 97:887-892.
232. Schwarz EM, Ritchlin CT. Clinical development of anti-rankl therapy. Arthritis Res. Ther 2007; 9:S7.
233. Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009; 27:1564-1571.
234. Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S. Randomized activecontrolled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007; 25:4431-4437.
235. Body JJ, Stopeck A, Fujiwara Y, Lipton A, Steger G, Viniegra M, Fan M, Dansey R, Susie J, Ada B. Results of a prospective, randomized, double-blind, doubledummy, Phase 3 study comparing denosumab with zoledronic acid for the treatment of breast cancer patients with bone metastases. Bone 2010; 46:S36-S37.
236. UK Clinical Research Network Study Portfolio. www.public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=1737.
237. Cleeland CS, Patrick DL, Fallowfield L, Clemons M, Lipton A, Masuda N, Qian Y, Braun A, Chung K. Comparing the effects of denosumab and zoledronic acid on pain interference with daily functioning in a randomized phase 3 trial of patients with breast cancer and bone metastases. Presented at 33rd Annual San Antonio Breast Cancer Symposium (SABCS). Abstract P1-13-01. San Antonio, TX, December 12, 2010.
238. Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH, McQueney MS, Foged NT, Delmas PD, Delaissé JM. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 1998; 273:32347-32352.
239. Wilson SR, Peters C, Saftig P, Bromme D. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem 2009; 284:2584-2592.
240. Le Gall C, Bellahcène A, Bonnelye E, Gasser JA, Castronovo V, Green J, Zimmermann J, Clèzardin P. A Cathepsin K inhibitor reduces breast cancer induced osteolysis and skeletal tumor burden. Cancer Res 2007; 67:9894-9902.
241. Deal C. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol 2009; 5:20-27.
242. Stoch SA, Zajic S, Stone J, Miller DL, Van Dyck K, Gutierrez MJ, De Decker M, Liu L, Liu Q, Scott BB, Panebianco D, Jin B, Duong LT, Gottesdiener K, Wagner JA., Effect of the Cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: Two double-blind, randomized, placebo-controlled Phase I studies. Clin Pharmacol Ther 2009; 86:175-182.
243. Jensen AB, Olmeo N, Wynne C, Ramirez G, Lebrecht A, Mehta A, He W, Song Y, Berd Y, Lombardi A. Effect of Cathepsin K inhibition on suppression of bone resorption in women with breast cancer and established bone metastases in a 4-week, double-blind, randomized controlled trial. J Clin Oncol [ASCO Annual Meeting Proceedings (Post-Meeting Edition)] 2008; 26:1023.
244. Votta BJ, Levy MA, Badger A, Bradbeer J, Dodds RA, James IE, Thompson S, Bossard MJ, Carr T, Connor JR, Tomaszek TA, Szewczuk L, Drake FH, Veber DF, Gowen M. Peptide aldehyde inhibitors of cathepsin K inhibit bone resorption both in vitro and in vivo. J Bone Miner Res 1997; 12:1396-1406.
245. Deal C. Future therapeutic targets in osteoporosis. Curr Opin Rheumatol 2009; 21:380-385.
246. Yeatman TJ. A renaissance for SRC. Nat Rev Cancer 2004; 4:470-480.
247. Bromann PA, Korkaya H, Courtneidge SA. The interplay between Src family kinases and receptor tyrosine kinases. Oncogene 2004; 23:7868-7957.
248. Wheeler DL, Iida M, Dunn EF. The role of Src in solid tumors. Oncologist 2009; 14:667-678.
249. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massagué J. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009; 16:67-78.
250. Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the csrc proto-oncogene leads to osteopetrosis in mice. Cell 1991; 64: 693-702.
251. Insogna KL, Sahni M, Grey AB, Tanaka S, Horne WC, Neff L, Mitnick M, Levy JB, Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and csrc-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. J Clin Invest 1997; 100:2476-2485.
252. Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H, Choi Y. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999; 4:1041-1049.
253. Schwartzberg PL, Xing L, Hoffmann O, Lowell CA, Garrett L, Boyce BF, Varmus HE. Rescue of osteoclast function by transgenic expression of kinase-deficient src in src-/-mutant mice. Genes Dev 1997; 11:2835-2844.
254. Lowe C, Yoneda T, Boyce BF, Chen H, Mundy GR, Soriano P: Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts. Proc Natl Acad Sci USA 1993; 90:4485-4489.
255. Araujo J, Logothetis C. Targeting Src signaling in metastatic bone disease. Int J Cancer 2009; 124:1-6.
256. Finn RS. Targeting Src in breast cancer. Ann Oncol 2008; 19:1379-1386.
257. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, Slamon DJ. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/"triple-negative" breast cancer cell lines growing in vitro. Breast Cancer Res Treat 2007; 105:319-326.
258. Rucci N, Recchia I, Angelucci A, Alamanou M, Del Fattore A, Fortunati D, Susa M, Fabbro D, Bologna M, Teti A. Inhibition of protein kinase c-Src reduces the incidence of breast cancer metastases and increases survival in mice: Implications for therapy. J Pharmacol Exp Ther 2006; 318:161-172.
259. Rucci N, Susa M, Teti A. Inhibition of protein kinase c-Src as a therapeutic approach for cancer and bone metastases. Anticancer Agents Med Chem 2008; 8:342-349.
260. Araujo J, Armstrong AJ, Braud EL, Posadas E, Lonberg M, Gallick GE, Trudel GC, Paliwal P, Agrawal S, Logothetis CJ. Dasatinib and docetaxel combination treatment for patients with castrationresistance progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol 2009; 27:249.
261. Spencer GJ, Utting JC, Etheridge SL, Arnett TR, Genever PG. Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 2006; 119:1283-1296.
262. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy Jr JD. Antibody based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 2007; 109:2106-2111.
263. Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, Mitsiades C, Prabhala R, Raje N, Anderson KC, Stover DR, Munshi NC. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 2009; 114:371-379.
264. Masaki T. The endothelin family: An overview. J Cardiovasc Pharmacol 2000; 35:S3-S5.
265. Clines GA, Mohammad KS, Bao Y, Stephens OW, Suva LJ, Shaughnessy JD Jr, Fox JW, Chirgwin JM, Guise TA. Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation. Mol Endocrinol 2007; 12:486-498.
266. Casey ML, Byrd W, MacDonald PC. Massive amounts of immunoreactive endothelin in human seminal fluid. J Clin Endocrinol Metab 1992; 74:223-225.
267. Prayer-Galetti T, Rossi GP, Belloni AS, Albertin G, Battanello W, Piovan V, Gardiman M, Pagano F. Gene expression and autoradiographic localization of endothelin-1 and its receptors A and B in the different zones of the normal human prostate. J Urol 1997; 157:2334-2339.
268. Nelson JB, Hedican SP, George DJ, Reddi AH, Piantadosi S, Eisenberger MA, Simons JW. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1995; 1:944-949.
269. Carducci MA, Padley RJ, Breul J, Vogelzang NJ, Zonnenberg BA, Daliani DD, Schulman CC, Nabulsi AA, Humerickhouse RA, Weinberg MA, Schmitt JL, Nelson JB. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol 2003; 21:679-689.
270. Nelson JB. Endothelin receptor antagonists. World J Urol 2005; 23:19-27.
271. Nelson JB, Nabulsi AA, Vogelzang NJ, Breul J, Zonnenberg BA, Daliani DD, Schulman CC, Carducci MA. Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol 2003; 169:1143-1149.
272. Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA, Sleep DJ, Isaacson JD, Nelson JB; Atrasentan Phase III Study Group Institutions. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 2007; 110:1959-1966.
273. James ND, Caty A, Borre M, Zonnenberg BA, Beuzeboc P, Morris T, Phung D, Dawson NA. Safety and efficacy of the specific endothelin-A receptor antagonist ZD4054 in patients with hormoneresistant prostate cancer and bone metastases who were pain free or mildly symptomatic: A double-blind, placebocontrolled, randomised, phase 2 trial. Eur Urol 2009; 55:1112-1123.
274. James ND, Caty A, Payne H, Borre M, Zonnenberg BA, Beuzeboc P, McIntosh S, Morris T, Phung D, Dawson NA. Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with metastatic castration-resistant prostate cancer and bone metastases who were painfree or mildly symptomatic for pain: A double-blind, placebo-controlled, randomized Phase II trial. BJU Int 2010; 106:966-973.
275. Neri P, Kumar S, Fulciniti MT, Vallet S, Chhetri S, Mukherjee S, Tai Y, Chauhan D, Tassone P, Venuta S, Munshi NC, Hideshima T, Anderson KC, Raje N. Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Clin Cancer Res 2007; 13:5903-5909.
276. Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, Podar K, Hideshima T, Chauhan D, Raje N, Schlossman R, Richardson P, Munshi NC, Anderson KC. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res 2006; 66:6675-6682.
277. Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massagué J, Mundy GR, Guise TA. TGF-b signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest 1999; 103:197-206.
278. Kang Y, He W, Tulley S, Gupta GP, Serganova I, Chen CR, Manova-Todorova K, Blasberg R, Gerald WL, Massagué J. Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci USA 2005; 102:13909-13914.
279. Deckers M, Van Dinther M, Buijs J, Que I, Löwik C, van der Pluijm G, ten Dijke P. The tumor suppressor smad4 is required for transforming growth factor b-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res 2006; 66:2202-2209.
280. Mourskaia AA, Dong Z, Ng S, Banville M, Zwaagstra JC, O'Connor-McCourt MD, Siegel PM. Transforming growth factor-b1 is the predominant isoform required for breast cancer cell outgrowth in bone. Oncogene 2009; 28:1005-1015.
281. Bandyopadhyay A, Agyin JK, Wang L, Tang Y, Lei X, Story BM, Cornell JE, Pollock BH, Mundy GR, Sun LZ. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-b type I receptor kinase inhibitor. Cancer Res 2006; 66:6714-6721.
282. Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, Ishikawa Y, Nomura K, Yokoo H, Shimizu T, Ogata E, Miyazono K, Shimizu K, Imamura T. Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Sci 2007; 98:127-133.
283. Welt C, Sidis Y, Keutmann H, Schneyer A. Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium. Exp Biol Med 2002; 227:724-752.
284. Vale W, Wiater E, Gray P, Harrison C, Bilezikjian L, Choe S. Activins and inhibins and their signaling. Ann NY Acad Sci 2004; 1038:142-147.
285. Harrison CA, Gray PC, Vale WW, Robertson DM. Antagonists of activin signalling: Mechanisms and potential biological applications. Trends Endocrinol Metab 2005; 16:73-78.
286. Baron R, Rawadi G. Targeting the Wnt/b-Catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007; 148:2635-2643.
287. Labbé E, Lock L, Letamendia A, Gorska AE, Gryfe R, Gallinger S, Moses HL, Attisano L. Transcriptional cooperation between the transforming growth factorbeta and Wnt pathways in mammary and intestinal tumorigenesis. Cancer Res 2007; 67:75-84.
288. Hirota M, Watanabe K, Hamada S, Sun Y, Strizzi L, Mancino M, Nagaoka T, Gonzales M, Seno M, Bianco C, Salomon DS. Smad2 functions as a co-activator of canonical Wnt/betacatenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300. Cell Signal 2008; 20:1632-1641.
289. Robinson DR, Zylstra CR, Williams BO. Wnt signaling and prostate cancer. Curr Drug Targets 2008; 9:571-580.
290. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: Components, mechanisms, and diseases. Dev Cell 2009; 17:9-26.
291. Mulivor AW, Barbosa D, Kumar R, Pearsall AE, Underwood KW, Ucran J, Seehra R, Pearsall R. RAP-011, a soluble activin receptor type IIA murine IgG-Fc fusion protein, is a novel bone anabolic agent that prevents bone loss and skeletal metastases in a mouse model of metastatic breast cancer. Bone 2009; 44:S221-S222.
292. Tsuchida K, Nakatani M, Hitachi K, Uezumi A, Sunada Y, Ageta H, Inokuchi K. Activin signaling as an emerging target for therapeutic interventions. Cell Commun Signal 2009; 7:15.
293. Nicks KM, Perrien DS, Akel NS, Suva LJ, Gaddy D. Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, activin and inhibin. Mol Cell Endocrinol 2009; 310:11-20.
294. Wang J, Loberg R, Taichman RS. The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis. Cancer Metastasis Rev 2006; 25:573-587.
295. Liang Z, Wu T, Lou H, Yu X, Taichman RS, Lau SK, Nie S, Umbreit J, Shim H. Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4. Cancer Res 2004; 64:4302-4308.
296. Sun YX, Schneider A, Jung Y, Wang J, Dai J, Wang J, Cook K, Osman NI, Koh-Paige AJ, Shim H, Pienta KJ, Keller ET, McCauley LK, Taichman RS. Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 2005; 20:318-329.
297. Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 2004; 64:8604-8612.
298. Huang EH, Singh B, Cristofanilli M, Gelovani J, Wei C, Vincent L, Cook KR, Lucci A. A CXCR4 antagonist CTCE-9908 inhibits primary tumor growth and metastasis of breast cancer. J Surg Res 2009; 155:231-236.
299. Richert MM, Vaidya KS, Mills CN, Wong D, Korz W, Hurst DR, Welch DR. Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone. Oncol Rep 2009; 21:761-767.
300. Wilson NM, Jung H, Ripsch MS, Miller RJ, White FA. CXCR4 signaling mediates morphine-induced tactile hyperalgesia. Brain Behav Immun 2011; 25:565-573.
301. Lipton A. Future treatment of bone metastases. Clin Cancer Res 2006; 12:6305s-6308s.
302. Mantyh PW. Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci 2006; 7:797-809.
303. von Moos R, Strasser F, Gillessen S, Zaugg K. Metastatic bone pain: Treatment options with an emphasis on bisphosphonates. Support Care Cancer 2008; 16:1105-1115.
304. Delaisse JM, Vaes G. Mechanism of mineral solubilization and matrix degradation in osteoclastic bone resorption. In: Rifkin BR, Gay CV (eds). Biology and Physiology of the Osteoclast. CRC Press, Boca Raton, 1992, pp 289-314.
305. Teitelbaum SL. Osteoclasts: What do they do and how do they do it? Am. J. Pathol 2007; 170:427-435.
306. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001; 413:203-210.
307. Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, Mantyh PW. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 2005; 25:3126-3131.
308. Niiyama Y, Kawamata T, Yamamoto J, Furuse S, Omote K, Namiki A. SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine on bone cancer pain. Br J Anaesth 2009; 102:251-258.
309. Jimenez-Andrade JM, Mantyh WG, Bloom AP, Ferng AS, Geffre CP, Mantyh PW. Bone cancer pain. Ann N Y Acad Sci 2010; 1198:173-181.
310. Halvorson KG, Kubota K, Sevcik MA, Lindsay TH, Sotillo JE, Ghilardi JR, Rosol TJ, Boustany L, Shelton DL, Mantyh PW. A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res 2005; 65:9426-9435.
311. Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM, Kubota K, Kuskowski MA, Boustany L, Shelton DL, Mantyh PW. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 2005; 115:128-141.
312. www.clinicaltrials.gov. Accessed April 2009. NCT00545129, NCT00830180.
313. Jimenez-Andrade JM, Bloom AP, Stake JI, Mantyh WG, Taylor RN, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW. Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci 2010; 30:14649-14656.
314. Ghilardi JR, Freeman KT, Jimenez-Andrade JM, Mantyh WG, Bloom AP, Kuskowski MA, Mantyh PW. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain. Mol Pain 2010; 6:87.
315. Kaan TK, Yip PK, Patel S, Davies M, Marchand F, Cockayne DA, Nunn PA, Dickenson AH, Ford AP, Zhong Y, Malcangio M, McMahon SB. Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain behaviour in rats. Brain 2010; 133:2549-2564.