{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:10:57Z","timestamp":1761581457304,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T00:00:00Z","timestamp":1471564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>Nine out of ten metastatic prostate cancer (PCa) patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE). SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC) patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ). Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.<\/jats:p>","DOI":"10.3390\/dj4030028","type":"journal-article","created":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T09:58:27Z","timestamp":1471600707000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Advantages and Disadvantages of Bone Protective Agents in Metastatic Prostate Cancer: Lessons Learned"],"prefix":"10.3390","volume":"4","author":[{"given":"Christian","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, University of Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Borgmann","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-3593","authenticated-orcid":false,"given":"Maximilian","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"H\u00f6fner","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Tsaur","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.urolonc.2005.09.003","article-title":"Reduced incidence of bony metastasis at initial prostate cancer diagnosis: Data from CaPSURE\u2122","volume":"24","author":"Ryan","year":"2006","journal-title":"Urol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1097\/01.ju.0000134888.22332.bb","article-title":"Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3478 consecutive patients: Long-term results","volume":"172","author":"Roehl","year":"2004","journal-title":"J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.clinthera.2006.10.018","article-title":"Luteinizing Hormone-Releasing Hormone Agonists in the Treatment of Prostate Cancer: A Review of Their Discovery, Development and Place in Therapy","volume":"28","author":"Moreau","year":"2006","journal-title":"Clin. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.eururo.2007.09.002","article-title":"EAU guidelines on prostate cancer","volume":"53","author":"Heidenreich","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(10)61389-X","article-title":"Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial","volume":"376","author":"Oudard","year":"2010","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S1470-2045(12)70379-0","article-title":"Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: Final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study","volume":"13","author":"Fizazi","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/PPO.0b013e31827f123e","article-title":"Bone targeted therapies in metastatic castration-resistant prostate cancer","volume":"19","author":"Rajpar","year":"2013","journal-title":"Cancer J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJMoa1207506","article-title":"Increased survival with enzalutamide in prostate cancer after chemotherapy","volume":"367","author":"Scher","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S1548-5315(12)70101-8","article-title":"The impact of bone metastases and seketal-related events on healthcare costs in prostate cancer patients receiving hormonal therapy","volume":"8","author":"Hagiwara","year":"2011","journal-title":"Community Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1093\/jnci\/94.19.1458","article-title":"A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma","volume":"94","author":"Saad","year":"2002","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_13","first-page":"317","article-title":"The cost of treating skeletal-related events in patients with prostate cancer","volume":"14","author":"Lage","year":"2008","journal-title":"Am. J. Manag. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1634\/theoncologist.2015-0327","article-title":"The clinical and economic impacts of skeletal-related events among medicare enrolees with prostate cancer metastatic to bone","volume":"21","author":"McDougall","year":"2016","journal-title":"Oncologist"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(10)62344-6","article-title":"Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, double-blind study","volume":"377","author":"Fizazi","year":"2011","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.eururo.2008.06.070","article-title":"Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate","volume":"54","author":"Walter","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1016\/j.joms.2007.03.006","article-title":"Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy","volume":"65","author":"Wang","year":"2007","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8580","DOI":"10.1200\/JCO.2005.02.8670","article-title":"Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors","volume":"23","author":"Bamias","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_20","first-page":"E351","article-title":"Osteonecrosis of the jaw as an adverse bisphosphonate event: Three cases of bone metastatic prostate cancer patients treated with zoledronic acid","volume":"12","author":"Villalobos","year":"2007","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1200\/JCO.2009.21.9584","article-title":"Longitudinal study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw","volume":"27","author":"Vahtsevanos","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0140-6736(11)61226-9","article-title":"Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: Results of a phase 3, randomised, placebo-controlled trial","volume":"379","author":"Smith","year":"2012","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/odi.12080","article-title":"Resource Utilization in Cancer Patients with Bisphosphonate-Associated Osteonecrosis of the Jaw","volume":"20","author":"Najm","year":"2014","journal-title":"Oral Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.joms.2014.04.031","article-title":"American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw\u20142014 Uptade","volume":"72","author":"Ruggiero","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00784-015-1563-8","article-title":"Bone scintigraphy predicts bisphosphonate-induced osteonecrosis of the jaw (BRONJ) in patients with metastatic castration-resistant prostate cancer (mCRPC)","volume":"20","author":"Thomas","year":"2016","journal-title":"Clin. Oral Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00784-009-0293-1","article-title":"Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study","volume":"14","author":"Stockmann","year":"2010","journal-title":"Clin. Oral Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.joms.2009.03.005","article-title":"Intravenous bisphosphonate-related osteonecrosis of the jaw: Bone scintigraphy as an early indicator","volume":"67","author":"Khoury","year":"2009","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s13139-012-0144-x","article-title":"Implications of three-phase bone scintigraphy for the diagnosis of bisphosphonate-related osteonecrosis of the jaw","volume":"46","author":"Hong","year":"2012","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.oooo.2012.05.017","article-title":"Intravenous bisphosphonate-related osteonecrosis of the jaw: Long-term follow-up of 109 patients","volume":"115","author":"Watters","year":"2013","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.bjoms.2009.07.020","article-title":"A survey of consultant members of the British association of oral and maxillofacial surgeons regarding bisphosphonate-induced osteonecrosis of the jaws","volume":"47","author":"Rogers","year":"2009","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1200\/JCO.2013.51.6500","article-title":"Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (alliance)","volume":"32","author":"Smith","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9501","DOI":"10.1200\/jco.2015.33.15_suppl.9501","article-title":"CALGB 70604 (Alliance): A randomized pahse III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer","volume":"33","author":"Himelstein","year":"2015","journal-title":"J. Clin. Oncol."}],"container-title":["Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-6767\/4\/3\/28\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:45Z","timestamp":1760210925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-6767\/4\/3\/28"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,19]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,9]]}},"alternative-id":["dj4030028"],"URL":"https:\/\/doi.org\/10.3390\/dj4030028","relation":{},"ISSN":["2304-6767"],"issn-type":[{"type":"electronic","value":"2304-6767"}],"subject":[],"published":{"date-parts":[[2016,8,19]]}}}