Indian Journal of Urology Users online:1811  
IJU
Home Current Issue Ahead of print Editorial Board Archives Symposia Guidelines Subscriptions Login 
Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
UROSCAN
Year : 2010  |  Volume : 26  |  Issue : 1  |  Page : 149-150
 

Antifracture agents for prostate cancer patients on androgen deprivation therapy


Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, U.P, India

Date of Web Publication23-Mar-2010

Correspondence Address:
Bhupendra P Singh
Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, U.P
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions

 

How to cite this article:
Singh BP, Goel A, Gupta A. Antifracture agents for prostate cancer patients on androgen deprivation therapy. Indian J Urol 2010;26:149-50

How to cite this URL:
Singh BP, Goel A, Gupta A. Antifracture agents for prostate cancer patients on androgen deprivation therapy. Indian J Urol [serial online] 2010 [cited 2019 Sep 21];26:149-50. Available from: http://www.indianjurol.com/text.asp?2010/26/1/149/60468

Smith MR, Egerdie B, Toriz NH, Feldman R, Tammela TL, Saad F, et al., the Denosumab HALT Prostate Cancer Study Group. Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer. N Engl J Med 2009;361:745-55. Aug 11. [In press] (10.1056/NEJMoa0809003)



   Summary Top


In this double-blind randomized multicenter study, effects of denosumab-a fully human monoclonal antibody against receptor activator of nuclear factor-kB ligand (RANKL), were seen on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. Patients were given either denosumab at a dose of 60 mg subcutaneously every six months or placebo with 734 patients in each group. Primary end point was change in bone mineral density at the lumbar spine at 24 months. Secondary end points were percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. Study found that at 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group compared to a loss of 1.0% in the placebo group (P < 0.001); significant differences between the two groups were seen at as early as one month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% CI, 0.19-0.78; P = 0.006). Rates of adverse events were similar between the two groups. Authors concluded that twice- yearly administration of denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.


   Comments Top


In randomized controlled trials, bisphosphonates (for example, pamidronate, zoledronic acid, and alendronate) and selective estrogen-receptor modulators (for example, raloxifene and toremifene) have been found to increase the bone mineral density of the hip and spine and decrease the bone turnover in men receiving androgen-deprivation therapy for prostate cancer.

Because of limited data on fracture prevention and lack of prospective data on natural history of bone loss and fractures in men receiving androgen-deprivation therapy neither evidence-based guidelines nor established standards of care exists and no approved therapy is indicated for reducing the risk of fracture in men receiving androgen-deprivation therapy for prostate cancer. However, studies have suggested that both oral bisphosphonates [1],[2] and teriparatide [3] may reduce the risk of fracture in men with osteoporosis, unrelated to androgen-deprivation therapy. Toremifene decreased the risk of new vertebral fractures by approximately 50% in men receiving androgen-deprivation therapy for prostate cancer. [4]

RANKL mediates osteoclast development, activity, and survival. As osteoporosis results, in part, from increased osteoclastic bone resorption, the inhibition of RANKL activity has been a therapeutic target. In addition to this study, Cummings et al., [5] also established the efficacy of denosumab, in reducing fractures, although in osteoporotic postmenopausal women. The beneficial effects of the denosumab appeared robust; seen as early as one month after starting therapy and were sustained for three years with significant increases in bone mineral density at all three measured bone sites including distal third of the radius, a site of predominantly cortical bone, for which both bisphosphonates [6] and selective estrogen-receptor modulators have not shown a positive effect. At 36 months, denosumab group had a 1.5% incidence of new vertebral fractures compared to 3.9% in the placebo group (62% decrease).

In the absence of head-to-head comparative studies, it is difficult to compare the antifracture efficacy of the various drugs. The risk reduction for vertebral fractures with denosumab equal to that reported for intravenous zoledronic acid [7] or teriparatide [8] and slightly greater than oral bisphosphonates. [9] For nonvertebral fractures, effect seems to be same for all these agents. [9] Thus, denosumab appears at least as efficacious as the best of the currently approved alternatives.

Although for dansosunab cost will be a limiting factor, it may be beneficial in terms of compliance (twice yearly subcutaneous self-administered like once-yearly intravenous zoledronic acid), side-effect profile (osteonecrosis of the jaw and atypical femoral subtrochanteric fracture seen with bisphosphonates), and use in renal insufficiency (cleared by nonrenal metabolism in contrast to bisphosphonates).

Except for eczema and cellulitis, serious infections have not been found to increase significantly by danosunab. [5] Further studies and surveillance is needed to directly address its use in renal insufficiency, to clarify any adverse impact on immune system (as RANKL is expressed on immune cells also) as well as its exact place in armamentarium of antifracture therapies in cancer prostate.

 
   References Top

1.Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000;343:604-10.  Back to cited text no. 1      
2.Ringe JD, Faber H, Farahmand P, Dorst A. Efficacy of risedronate in men with primary and secondary osteoporosis: r0 esults of a 1-year study. Rheumatol Int 2006;26:427-31.  Back to cited text no. 2  [PUBMED]    
3.Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, Lindsay R, Mitlak BH. et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: t0 reatment and discontinuation of therapy. Osteoporos Int 2005;16:510-6.  Back to cited text no. 3  [PUBMED]    
4.Smith M, Morton RA Jr, Wallace H, Rodriguez D, Hancock M, Steiner M. A phase III randomized controlled trial of toremifene to prevent fractures and other adverse effects of androgen therapy in men with prostate cancer. Presented at the American Association for Cancer Research 100 th Annual Meeting, San Diego, CA, April 12- 62008.  Back to cited text no. 4      
5.Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-65. (10.1056/NEJMoa0809493).  Back to cited text no. 5      
6.Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med 2007;146:416-24.  Back to cited text no. 6      
7.Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-22.   Back to cited text no. 7      
8.Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434-41.  Back to cited text no. 8      
9.Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: s0 imilarities and differences and their potential influences on clinical efficacy. Osteoporos Int 2008;19:733-59.  Back to cited text no. 9      




 

Top
Print this article  Email this article
Previous article Next article

    

 
   Search
 
   Next article
   Previous article 
   Table of Contents
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (574 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Summary
    Comments
    References

 Article Access Statistics
    Viewed1404    
    Printed57    
    Emailed1    
    PDF Downloaded84    
    Comments [Add]    

Recommend this journal

HEALTHWARE INDIA