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Use of Bisphosphonates and Reduced Risk of Colorectal Cancer (CRC)

Bisphosphonates are FDA-approved in the treatment of osteoporosis, for bone loss associated with cancer therapy and bone metastasis.  Nitrogen-containing bisphosphonates are thought to work by inhibition of the mevalonate pathway; these agents also have been linked to inhibition of cancer growth by their action on angiogenesis and tumor cell adhesion as well as their ability to induce apoptosis.1 Retrospective studies have reported that the use of oral bisphosphonates used to prevent bone loss and fractures in postmenopausal women with osteoporosis also reduced the risk of developing breast cancer by a significant percentage, suggesting that bisphosphonates may have inhibiting effects on this tumor type.2 Rennert and colleagues3 recently reported on the association between bisphosphonates and the risk of CRC in the Journal of Clinical Oncology.  The authors discuss the results of the Molecular Epidemiology of Colorectal Cancer study, a population-based, case-control study of patients with CRC in northern Israel. Long-term use of bisphosphonates before diagnosis was assessed in a subset of 933 pairs of postmenopausal female patients and controls, using pharmacy records and questionnaires.3 The overall study response rate was 75.5% for all eligible patients. Pharmacy records provided information on all bisphosphonate users who had filled at least three prescriptions before diagnosis of CRC.  Alendronate was the primary oral bisphosphonate used by the study participants; 60% of the patients used 10 mg daily, 40% used 70 mg weekly.  Statin use was also studied since these agents use the mevalonate pathway as well.3


The study found a significant reduction in the risk of CRC; relative risk (RR) of 0.67 (95% CI, 0.51 to 0.88).  The significant negative association with CRC risk was found only in those patients who had used bisphosphonates for more than one year.  Both bisphosphonates and the use of statin agents demonstrated a strong negative association; however the use of the drugs combined did not provide further risk reduction.3 Overall, the data show that oral bisphosphonate use in postmenopausal women was associated with a 59% reduction in risk after adjustment for many known risk factors for CRC.

ManageCRC Commentary

Although treatment of CRC has improved, prevention of this common tumor type is preferable to receiving combinations of surgery and chemotherapy for nodal disease.  Studies of aspirin and its protective effect against the development of CRC have been published; the protective effect of COX-2 inhibitors against the formation of precancerous polyps has also been documented.4-5 Despite the potential positive effects of the previously mentioned agents, these drugs also have adverse side effects associated with their use such as gastrointestinal bleeding 4-5 Similarly, bisphosphonates have adverse effects associated with their use.  Although rare, osteonecrosis of the jaw (ONJ) can occur.  Recently, an association between fractures and long term use has also been identified.  Rennert and colleagues have found an intriguing association between bisphosphonate use and the reduction of the risk of CRC; more research is needed to further define the role of this class of drug and chemoprevention in the healthy adult.


  1. Smith, MR. Antitumor activity of bisphosphonates. Clin Cancer Res. 2003; 9: 5433-5434. Free full text available at: http://clincancerres.aacrjournals.org/content/9/15/5433.full.pdf+html.
  2. Chlebowski, RT, Chen, Z, Cauley, JA, et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol. 2010; 28: 3582-3590. doi: 10.1200/JCO.2010.28.2095  Free full text available at: http://jco.ascopubs.org/content/28/22/3582.full.pdf+html
  3. Rennert, G, Pinchev, M, Rennert, HS, et al.  Use of bisphosphonates and reduced risk of colorectal cancer. J Clin Oncol. 2011, published online before print February 11, 2011. doi:10.1200/JCO.2010.33.7485  Link to abstract at: http://www.ncbi.nlm.nih.gov/pubmed/21321296.
  4. Chan, AT, Ogino, S, Fuchs, CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. NEJM. 2007; 356: 2131-2142. Link to free full text at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa067208
  5. Brown, JR & DuBois, RN. COX-2: A molecular target for colorectal cancer prevention. J Clin Oncol. 2005; 23: 2840-2855. doi:10.1200/JCO.2005.09.051 Free full text available at: http://jco.ascopubs.org/content/23/12/2840.full.pdf+html

Article Created On : 3/3/2011 9:28:05 AM             Article Updated On : 3/3/2011 9:28:05 AM