Cancer Treatment-Induced Bone Loss (CTIBL) in Prostate Cancer: Pathophysiology, Preclinical Findings, and Treatment with Zoledronic Acid  Theresa A. Guise, James A. Eastham  European Urology Supplements  Volume 3, Issue 5, Pages 46-54 (November 2004) DOI: 10.1016/j.eursup.2004.08.012 Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 1 Hormone-naive patients with advanced prostate cancer have significantly lower bone mineral density (BMD) compared with age-matched controls. Using forearm densitometry, BMD was expressed as the standard deviation (SD) below the mean for a healthy population age 20 to 40 years (T-score) and for a healthy age-matched population (Z-score). *p < 0.05. Data from Hussain et al. [11]. European Urology Supplements 2004 3, 46-54DOI: (10.1016/j.eursup.2004.08.012) Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 2 Pathophysiology of bone loss resulting from androgen deprivation. During normal bone remodeling, osteoclast-mediated bone resorption is followed by the repair of bone by osteoblasts. Androgen deprivation results in excessive osteoclast-mediated bone resorption that cannot be adequately repaired by osteoblasts. European Urology Supplements 2004 3, 46-54DOI: (10.1016/j.eursup.2004.08.012) Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 3 Androgen deprivation therapy (ADT) causes significant bone loss and increased bone resorption in patients with prostate cancer compared with age-matched controls. (A) Patients receiving a gonadotropin-releasing hormone (GnRH) analogue experienced significant reductions in total hip bone mineral density (BMD) after 1 year of treatment. (B) Bone loss was associated with a significant increase in the biochemical marker of bone resorption, N-telopeptide, at 6 months and 1 year after initiation of treatment. *p < 0.001; †p < 0.05. Adapted with permission from Mittan et al. [38]. European Urology Supplements 2004 3, 46-54DOI: (10.1016/j.eursup.2004.08.012) Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 4 Effect of intravenous bisphosphonate therapy on bone mineral density (BMD) in patients with prostate cancer receiving androgen deprivation therapy. (A) Treatment with pamidronate prevented the decrease of BMD from baseline experienced by patients not receiving bisphosphonate therapy (control group) [56]. (B) Treatment with zoledronic acid significantly increased mean BMD from baseline compared with placebo [57]. *p ≤ 0.005 for comparison between pamidronate and control; †p < 0.001 for comparison between zoledronic acid and placebo. Adapted with permission from Smith et al. [57]. European Urology Supplements 2004 3, 46-54DOI: (10.1016/j.eursup.2004.08.012) Copyright © 2004 Elsevier B.V. Terms and Conditions