Therapies for Bone Metastasis in Prostate Cancer: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor: , , , , , , ,

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients’ well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. 

  • prostate cancer
  • bone metastasis
  • bone-targeted therapies
  • skeletal-related event

1. Introduction

Prostate cancer (PCa) is a prevalent malignant tumor in the United States, ranking second in terms of mortality rate after lung cancer [1]. There exists a significant disparity in the occurrence rate of prostate cancer between China (10.2/100,000) and North America (73.0/100,000), with both the incidence and mortality rates showing a consistent upward trend in recent years [2][3]. The 2014 China Multicenter Report revealed that a significant proportion of Chinese patients (approximately 30.5%) diagnosed with prostate cancer had already developed distant metastases at the time of initial diagnosis, which is considerably higher compared to the rates observed in North America [4]. Nowadays, the treatment options for patients diagnosed with metastatic prostate cancer (mPCa) have shown significant advancements in recent years. Androgen deprivation therapy (ADT) serves as the primary treatment for this condition. Additional treatment options encompass chemotherapy, new generation hormone therapy, radium-223, and, more recently, radioligand therapy. Special considerations should be directed toward the management of bone health and the prevention of treatment-induced bone loss in these patients [5]. Among individuals diagnosed with castration-resistant prostate cancer (CRPC), bone metastasis is commonly detected in 70% to 90% of patients through imaging examinations [6]. Bone metastases give rise to the occurrence of skeletal-related events (SREs), which encompass severe pain, pathological fracture, spinal cord/intervertebral nerve compression, and hypercalcemia [5]. Preventing and reducing the occurrence of SREs, relieving pain caused by bone metastases, and improving patients’ quality of life are the goals of treatment. The management of bone metastases in prostate cancer has undergone significant advancements due to the enhanced comprehension of the disease’s progression, signaling pathways, mutational characteristics, and mechanisms of drug resistance. Table 1 and Figure 1 summarize the main pathways and mechanisms of action of the principal PC therapeutic agents. However, there exists a dearth of data analysis pertaining to drug trials and their progression over the previous decade. 
Figure 1. Main mechanisms of therapeutic agents for prostate cancer.
Table 1. Drugs and their mechanisms of actions against prostate cancer.

This entry is adapted from the peer-reviewed paper 10.3390/cancers16030627


  1. Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 2023, 73, 17–48.
  2. Zhu, Y.; Mo, M.; Wei, Y.; Wu, J.; Pan, J.; Freedland, S.J.; Zheng, Y.; Ye, D. Epidemiology and genomics of prostate cancer in Asian men. Nat. Rev. Urol. 2021, 18, 282–301.
  3. Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin. 2016, 66, 115–132.
  4. Chen, R.; Ren, S.; Yiu, M.K.; Fai, N.C.; Cheng, W.S.; Ian, L.H.; Naito, S.; Matsuda, T.; Kehinde, E.; Kural, A.; et al. Prostate cancer in Asia: A collaborative report. Asian J. Urol. 2014, 1, 15–29.
  5. Coleman, R.; Hadji, P.; Body, J.J.; Santini, D.; Chow, E.; Terpos, E.; Oudard, S.; Bruland, Ø.; Flamen, P.; Kurth, A.; et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann. Oncol. 2020, 31, 1650–1663.
  6. Weilbaecher, K.N.; Guise, T.A.; McCauley, L.K. Cancer to bone: A fatal attraction. Nat. Rev. Cancer 2011, 11, 411–425.
  7. Tran, C.; Ouk, S.; Clegg, N.J.; Chen, Y.; Watson, P.A.; Arora, V.; Wongvipat, J.; Smith-Jones, P.M.; Yoo, D.; Kwon, A.; et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009, 324, 787–790.
  8. Armstrong, A.J.; Szmulewitz, R.Z.; Petrylak, D.P.; Holzbeierlein, J.; Villers, A.; Azad, A.; Alcaraz, A.; Alekseev, B.; Iguchi, T.; Shore, N.D.; et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J. Clin. Oncol. 2019, 37, 2974–2986.
  9. Armstrong, A.J.; Shore, N.D.; Szmulewitz, R.Z.; Petrylak, D.P.; Holzbeierlein, J.; Villers, A.; Azad, A.; Alcaraz, A.; Alekseev, B.; Iguchi, T.; et al. Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses. J. Urol. 2021, 205, 1361–1371.
  10. Beer, T.M.; Armstrong, A.J.; Rathkopf, D.E.; Loriot, Y.; Sternberg, C.N.; Higano, C.S.; Iversen, P.; Bhattacharya, S.; Carles, J.; Chowdhury, S.; et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N. Engl. J. Med. 2014, 371, 424–433.
  11. Taplin, M.E.; Armstrong, A.J.; Lin, P.; Krivoshik, A.; Phung, D.; Parli, T.; Tombal, B.; Beer, T.M. Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo. J. Urol. 2017, 198, 1324–1332.
  12. Fizazi, K.; Tran, N.; Fein, L.; Matsubara, N.; Rodriguez-Antolin, A.; Alekseev, B.Y.; Özgüroğlu, M.; Ye, D.; Feyerabend, S.; Protheroe, A.; et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. 2017, 377, 352–360.
  13. Chi, K.N.; Protheroe, A.; Rodríguez-Antolín, A.; Facchini, G.; Suttman, H.; Matsubara, N.; Ye, Z.; Keam, B.; Damião, R.; Li, T.; et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): An international, randomised phase 3 trial. Lancet Oncol. 2018, 19, 194–206.
  14. James, N.D.; de Bono, J.S.; Spears, M.R.; Clarke, N.W.; Mason, M.D.; Dearnaley, D.P.; Ritchie, A.W.S.; Amos, C.L.; Gilson, C.; Jones, R.J.; et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N. Engl. J. Med. 2017, 377, 338–351.
  15. Ryan, C.J.; Smith, M.R.; de Bono, J.S.; Molina, A.; Logothetis, C.J.; de Souza, P.; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 2013, 368, 138–148.
  16. Clegg, N.J.; Wongvipat, J.; Joseph, J.D.; Tran, C.; Ouk, S.; Dilhas, A.; Chen, Y.; Grillot, K.; Bischoff, E.D.; Cai, L.; et al. ARN-509: A novel antiandrogen for prostate cancer treatment. Cancer Res. 2012, 72, 1494–1503.
  17. Chi, K.N.; Agarwal, N.; Bjartell, A.; Chung, B.H.; Pereira de Santana Gomes, A.J.; Given, R.; Juárez Soto, Á.; Merseburger, A.S.; Özgüroğlu, M.; Uemura, H.; et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. 2019, 381, 13–24.
  18. Antonarakis, E.S.; Lu, C.; Luber, B.; Wang, H.; Chen, Y.; Zhu, Y.; Silberstein, J.L.; Taylor, M.N.; Maughan, B.L.; Denmeade, S.R.; et al. Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men with Metastatic Castration-Resistant Prostate Cancer Treated with First- and Second-Line Abiraterone and Enzalutamide. J. Clin. Oncol. 2017, 35, 2149–2156.
  19. Antonarakis, E.S.; Lu, C.; Wang, H.; Luber, B.; Nakazawa, M.; Roeser, J.C.; Chen, Y.; Mohammad, T.A.; Chen, Y.; Fedor, H.L.; et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med. 2014, 371, 1028–1038.
  20. Bastos, D.A.; Antonarakis, E.S. Galeterone for the treatment of advanced prostate cancer: The evidence to date. Drug Des. Dev. Ther. 2016, 10, 2289–2297.
  21. Taplin, M.E.; Antonarakis, E.S.; Ferrante, K.J.; Horgan, K.; Blumenstein, B.; Saad, F.; Luo, J.; de Bono, J.S. Androgen Receptor Modulation Optimized for Response-Splice Variant: A Phase 3, Randomized Trial of Galeterone versus Enzalutamide in Androgen Receptor Splice Variant-7-expressing Metastatic Castration-resistant Prostate Cancer. Eur. Urol. 2019, 76, 843–851.
  22. Denmeade, S.R. Bipolar androgen therapy in the treatment of prostate cancer. Clin. Adv. Hematol. Oncol. 2018, 16, 408–411.
  23. Markowski, M.C.; Wang, H.; Sullivan, R.; Rifkind, I.; Sinibaldi, V.; Schweizer, M.T.; Teply, B.A.; Ngomba, N.; Fu, W.; Carducci, M.A.; et al. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. Eur. Urol. 2021, 79, 692–699.
  24. Teply, B.A.; Wang, H.; Luber, B.; Sullivan, R.; Rifkind, I.; Bruns, A.; Spitz, A.; DeCarli, M.; Sinibaldi, V.; Pratz, C.F.; et al. Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: An open-label, phase 2, multicohort study. Lancet Oncol. 2018, 19, 76–86.
  25. Faris, J.E.; Smith, M.R. Metabolic sequelae associated with androgen deprivation therapy for prostate cancer. Curr. Opin. Endocrinol. Diabetes Obes. 2010, 17, 240–246.
  26. Saylor, P.J.; Smith, M.R. Metabolic complications of androgen deprivation therapy for prostate cancer. J. Urol. 2013, 189, S34–S42; discussion S43–S44.
  27. Rothermundt, C.; Hayoz, S.; Templeton, A.J.; Winterhalder, R.; Strebel, R.T.; Bärtschi, D.; Pollak, M.; Lui, L.; Endt, K.; Schiess, R.; et al. Metformin in chemotherapy-naive castration-resistant prostate cancer: A multicenter phase 2 trial (SAKK 08/09). Eur. Urol. 2014, 66, 468–474.
  28. Li, K.; Si-Tu, J.; Qiu, J.; Lu, L.; Mao, Y.; Zeng, H.; Chen, M.; Lai, C.; Chang, H.J.; Wang, D. Statin and metformin therapy in prostate cancer patients with hyperlipidemia who underwent radiotherapy: A population-based cohort study. Cancer Manag. Res. 2019, 11, 1189–1197.
  29. Crawley, D.; Chandra, A.; Loda, M.; Gillett, C.; Cathcart, P.; Challacombe, B.; Cook, G.; Cahill, D.; Santa Olalla, A.; Cahill, F.; et al. Metformin and longevity (METAL): A window of opportunity study investigating the biological effects of metformin in localised prostate cancer. BMC Cancer 2017, 17, 494.
  30. Gillessen, S.; Gilson, C.; James, N.; Adler, A.; Sydes, M.R.; Clarke, N. Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. Eur. Urol. 2016, 70, 906–908.
  31. Tannock, I.F.; de Wit, R.; Berry, W.R.; Horti, J.; Pluzanska, A.; Chi, K.N.; Oudard, S.; Théodore, C.; James, N.D.; Turesson, I.; et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl. J. Med. 2004, 351, 1502–1512.
  32. de Bono, J.S.; Oudard, S.; Ozguroglu, M.; Hansen, S.; Machiels, J.P.; Kocak, I.; Gravis, G.; Bodrogi, I.; Mackenzie, M.J.; Shen, L.; et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010, 376, 1147–1154.
  33. Climent, M.; Pérez-Valderrama, B.; Mellado, B.; Fernández Parra, E.M.; Fernández Calvo, O.; Ochoa de Olza, M.; Muinelo Romay, L.; Anido, U.; Domenech, M.; Hernando Polo, S.; et al. Weekly cabazitaxel plus prednisone is effective and less toxic for ‘unfit’ metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial. Eur. J. Cancer 2017, 87, 30–37.
  34. Gravis, G.; Fizazi, K.; Joly, F.; Oudard, S.; Priou, F.; Esterni, B.; Latorzeff, I.; Delva, R.; Krakowski, I.; Laguerre, B.; et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): A randomised, open-label, phase 3 trial. Lancet Oncol. 2013, 14, 149–158.
  35. Sweeney, C.J.; Chen, Y.H.; Carducci, M.; Liu, G.; Jarrard, D.F.; Eisenberger, M.; Wong, Y.N.; Hahn, N.; Kohli, M.; Cooney, M.M.; et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N. Engl. J. Med. 2015, 373, 737–746.
  36. Kyriakopoulos, C.E.; Chen, Y.H.; Carducci, M.A.; Liu, G.; Jarrard, D.F.; Hahn, N.M.; Shevrin, D.H.; Dreicer, R.; Hussain, M.; Eisenberger, M.; et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J. Clin. Oncol. 2018, 36, 1080–1087.
  37. Clarke, N.W.; Ali, A.; Ingleby, F.C.; Hoyle, A.; Amos, C.L.; Attard, G.; Brawley, C.D.; Calvert, J.; Chowdhury, S.; Cook, A.; et al. Corrigendum to Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: Long-term survival results from the STAMPEDE trial. Ann. Oncol. 2020, 31, 442.
  38. Smith, M.R.; Hussain, M.; Saad, F.; Fizazi, K.; Sternberg, C.N.; Crawford, E.D.; Kopyltsov, E.; Park, C.H.; Alekseev, B.; Montesa-Pino, Á.; et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N. Engl. J. Med. 2022, 386, 1132–1142.
  39. Fizazi, K.; Foulon, S.; Carles, J.; Roubaud, G.; McDermott, R.; Fléchon, A.; Tombal, B.; Supiot, S.; Berthold, D.; Ronchin, P.; et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2022, 399, 1695–1707.
  40. Sweeney, C.J.; Martin, A.J.; Stockler, M.R.; Begbie, S.; Cheung, L.; Chi, K.N.; Chowdhury, S.; Frydenberg, M.; Horvath, L.G.; Joshua, A.M.; et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): An international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023, 24, 323–334.
  41. Davis, I.D.; Martin, A.J.; Stockler, M.R.; Begbie, S.; Chi, K.N.; Chowdhury, S.; Coskinas, X.; Frydenberg, M.; Hague, W.E.; Horvath, L.G.; et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N. Engl. J. Med. 2019, 381, 121–131.
  42. Riaz, I.B.; Naqvi, S.A.A.; He, H.; Asghar, N.; Siddiqi, R.; Liu, H.; Singh, P.; Childs, D.S.; Ravi, P.; Hussain, S.A.; et al. First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer: A Living Systematic Review and Network Meta-analysis. JAMA Oncol. 2023, 9, 635–645.
  43. Zustovich, F.; Pastorelli, D. Therapeutic management of bone metastasis in prostate cancer: An update. Expert Rev. Anticancer Ther. 2016, 16, 1199–1211.
  44. Lassemillante, A.C.; Doi, S.A.; Hooper, J.D.; Prins, J.B.; Wright, O.R. Prevalence of osteoporosis in prostate cancer survivors II: A meta-analysis of men not on androgen deprivation therapy. Endocrine 2015, 50, 344–354.
  45. Lee, H.; McGovern, K.; Finkelstein, J.S.; Smith, M.R. Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer 2005, 104, 1633–1637.
  46. Walsh, P.C. Risk of fracture after androgen deprivation for prostate cancer. J. Urol. 2005, 174, 929–930.
  47. Finianos, A.; Aragon-Ching, J.B. Zoledronic acid for the treatment of prostate cancer. Expert Opin. Pharmacother. 2019, 20, 657–666.
  48. Wang, F.; Chen, W.; Chen, H.; Mo, L.; Jin, H.; Yu, Z.; Li, C.; Liu, Q.; Duan, F.; Weng, Z. Comparison between zoledronic acid and clodronate in the treatment of prostate cancer patients with bone metastases. Med. Oncol. 2013, 30, 657.
  49. Kamba, T.; Kamoto, T.; Maruo, S.; Kikuchi, T.; Shimizu, Y.; Namiki, S.; Fujimoto, K.; Kawanishi, H.; Sato, F.; Narita, S.; et al. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: Results of the ZAPCA trial. Int. J. Clin. Oncol. 2017, 22, 166–173.
  50. Smith, M.R.; Halabi, S.; Ryan, C.J.; Hussain, A.; Vogelzang, N.; Stadler, W.; Hauke, R.J.; Monk, J.P.; Saylor, P.; Bhoopalam, N.; et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (alliance). J. Clin. Oncol. 2014, 32, 1143–1150.
  51. Denham, J.W.; Joseph, D.; Lamb, D.S.; Spry, N.A.; Duchesne, G.; Matthews, J.; Atkinson, C.; Tai, K.H.; Christie, D.; Kenny, L.; et al. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial. Lancet Oncol 2019, 20, 267–281.
  52. James, N.D.; Pirrie, S.J.; Pope, A.M.; Barton, D.; Andronis, L.; Goranitis, I.; Collins, S.; Daunton, A.; McLaren, D.; O’Sullivan, J.; et al. Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer with Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both: The TRAPEZE Randomized Clinical Trial. JAMA Oncol. 2016, 2, 493–499.
  53. Wirth, M.; Tammela, T.; Cicalese, V.; Gomez Veiga, F.; Delaere, K.; Miller, K.; Tubaro, A.; Schulze, M.; Debruyne, F.; Huland, H.; et al. Prevention of bone metastases in patients with high-risk nonmetastatic prostate cancer treated with zoledronic acid: Efficacy and safety results of the Zometa European Study (ZEUS). Eur. Urol. 2015, 67, 482–491.
  54. Cornford, P.; van den Bergh, R.C.N.; Briers, E.; Van den Broeck, T.; Cumberbatch, M.G.; De Santis, M.; Fanti, S.; Fossati, N.; Gandaglia, G.; Gillessen, S.; et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur. Urol. 2021, 79, 263–282.
  55. Okegawa, T.; Higaki, M.; Matsumoto, T.; Kase, H.; Murata, A.; Noda, K.; Noda, H.; Asaoka, H.; Oshi, M.; Tomoishi, J.; et al. Zoledronic acid improves clinical outcomes in patients with bone metastatic hormone-naïve prostate cancer in a multicenter clinical trial. Anticancer Res. 2014, 34, 4415–4420.
  56. Nozawa, M.; Inagaki, T.; Nagao, K.; Nishioka, T.; Komura, T.; Esa, A.; Kitagawa, M.; Imanishi, M.; Uekado, Y.; Ogawa, T.; et al. Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis. Int. J. Clin. Oncol. 2014, 19, 693–701.
  57. Saad, F.; Segal, S.; Eastham, J. Prostate-specific antigen kinetics and outcomes in patients with bone metastases from castration-resistant prostate cancer treated with or without zoledronic acid. Eur. Urol. 2014, 65, 146–153.
  58. Joseph, J.S.; Lam, V.; Patel, M.I. Preventing Osteoporosis in Men Taking Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis. Eur. Urol. Oncol. 2019, 2, 551–561.
  59. Lacey, D.L.; Timms, E.; Tan, H.L.; Kelley, M.J.; Dunstan, C.R.; Burgess, T.; Elliott, R.; Colombero, A.; Elliott, G.; Scully, S.; et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93, 165–176.
  60. Lipton, A.; Fizazi, K.; Stopeck, A.T.; Henry, D.H.; Smith, M.R.; Shore, N.; Martin, M.; Vadhan-Raj, S.; Brown, J.E.; Richardson, G.E.; et al. Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur. J. Cancer 2016, 53, 75–83.
  61. Himelstein, A.L.; Foster, J.C.; Khatcheressian, J.L.; Roberts, J.D.; Seisler, D.K.; Novotny, P.J.; Qin, R.; Go, R.S.; Grubbs, S.S.; O’Connor, T.; et al. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients with Bone Metastases: A Randomized Clinical Trial. JAMA 2017, 317, 48–58.
  62. Clemons, M.; Liu, M.; Stober, C.; Pond, G.; Jemaan Alzahrani, M.; Ong, M.; Ernst, S.; Booth, C.; Mates, M.; Abraham Joy, A.; et al. Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer. J. Bone Oncol. 2021, 30, 100388.
This entry is offline, you can click here to edit this entry!
Video Production Service