Skip to main content
SpringerLink
Log in

Background to and Management of Treatment-Related Bone Loss in Prostate Cancer

  • Therapy In Practice
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Prostate cancer is a common disease among older men. Androgen suppression by either orchiectomy or administration of luteinising hormone—releasing hormone (LHRH) analogues is the mainstay of treatment. Since the use of prostate-specific antigen (PSA) serum testing has become widespread, however, the timing of endocrine therapy has expanded considerably to include patients with limited involvement of extraprostatic sites and patients presenting an isolated elevation of PSA after radical treatments. These patients are expected to be treated for a long time, since they have a rather low risk of disease progression and there is no recommended time limit for LHRH analogue therapy. The long-term adverse effects of androgen deprivation therapy, therefore, deserve more attention than they have received in the past.

Osteoporosis represents a special concern for men with prostate cancer receiving androgen deprivation therapy. The rate of bone loss in these men seems to markedly exceed that associated with menopause in women, and fractures occur more frequently than in the healthy elderly male population. Serial bone mineral density (BMD) evaluation could allow the detection of patients with prostate cancer who are at greater risk of osteoporosis and adverse skeletal events after androgen deprivation therapy, such as patients already osteopenic orosteoporotic at baseline and men with rapid bone loss during treatment. BMD evaluated during treatment could also be a potential surrogate parameter of antiosteoporotic therapeutic efficacy.

Treatment of bone loss induced by androgen deprivation comprises general prevention measures, antiosteoporotic drugs and the use of alternative endocrine therapies. Optimising lifestyle and diet is important, although it cannot completely prevent bone loss. Patients with nonsevere bone disease may benefit from calcium and vitamin D supplements. Men who are osteoporotic before androgen deprivation or men becoming osteoporotic during treatment and/or experiencing adverse skeletal events may also require bisphosphonates. The effectiveness of these drugs in preventing fractures has been shown in a single randomised study involving patients with osteoporosis, but it has not yet been established in a prostatic cancer population without bone metastases given androgen deprivation therapy.

Different forms of endocrine therapy such as low-dose estrogens, anti-androgens and intermittent androgen ablation are under investigation. They could offer the advantage of avoiding (or limiting) treatment-related bone loss. In our opinion, however, the data available so far are not robust enough to recommend these alternative endocrine therapies instead of standard androgen deprivation in routine clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Table III

Similar content being viewed by others

References

  1. Crocetti E, Buiatti E, Amorosi A. Prostate cancer: population-based survival rates in central Italy. Tumori 1995; 81: 81–5

    PubMed  CAS  Google Scholar 

  2. Dennis LK, Resnick MI. Analysis of recent trends in prostate cancer incidence and mortality. Prostate 2000; 42: 247–52

    Article  PubMed  CAS  Google Scholar 

  3. Small EJ. Prostate cancer: incidence, management and outcomes. Drugs Aging 1998; 13(1): 71–81

    Article  PubMed  CAS  Google Scholar 

  4. Denis LJ. Staging and prognosis of prostate cancer. Eur Urol 1993; 24 Suppl. 2: 13–8

    PubMed  Google Scholar 

  5. Van Cangh PJ, Gala JL, Tombal B. Immediate vs delayed androgen deprivation for prostate cancer. Prostate 2000; Suppl. 10: 19–25

    Google Scholar 

  6. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281: 1591–7

    Article  PubMed  CAS  Google Scholar 

  7. Meltzer D, Egleston B, Abballa I. Patterns of prostate cancer treatment by clinical stage and age. Am J Public Health 2001; 91: 126–8

    Article  PubMed  CAS  Google Scholar 

  8. Whitmore WF. Natural history and staging of prostate cancer. Urol Clin North Am 1984; 11: 205–20

    PubMed  Google Scholar 

  9. Taplin ME, Shuk-Mei H. The endocrinology of prostate cancer. J Clin Endocrinol Metab 2001; 86: 3467–77

    Article  PubMed  CAS  Google Scholar 

  10. Matsushima H, Goto T, Hosaka Y, et al. Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation. Cancer 1999; 85: 1822–7

    Article  PubMed  CAS  Google Scholar 

  11. Prostate Cancer Trialists Collaborative Group. Maximum androgen blockade in advanced cancer: an overview of the randomised trials. Lancet 2000; 355: 1491–8

    Article  Google Scholar 

  12. Galbraith SM, Duchesne GM. Androgens and prostate cancer: biology, pathology and hormonal therapy. Eur J Cancer 1997; 33: 545–54

    Article  PubMed  CAS  Google Scholar 

  13. The Medical Research Council Party Investigators Group. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. Br J Urol 1997; 79: 235–46

    Article  Google Scholar 

  14. Bolla M, Gonzales D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997; 337: 295–300

    Article  PubMed  CAS  Google Scholar 

  15. Messing EM, Manola J, Sarosdy M, et al. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999; 341: 1781–8

    Article  PubMed  CAS  Google Scholar 

  16. Wasson JH, Fowler FJ, Barry MJ. Androgen deprivation therapy for asymptomatic advanced prostate cancer in the prostate specific antigen era: a national survey of urologist beliefs and practices. J Urol 1998; 159: 1993–7

    Article  PubMed  CAS  Google Scholar 

  17. Stege R. Potential side effects of endocrine treatment of long duration in prostate cancer. Prostate 2000; Suppl. 10: 38–42

    Google Scholar 

  18. Seeman E. Osteoporosis in men: epidemiology, pathophysiology, and treatment possibilities. Am J Med 1993; 95 Suppl. 5A: 22–8

    Article  Google Scholar 

  19. Selby PL, Davies M, Adams JE. Do men and women fracture bones at similar bone densities? Osteoporos Int 2000; 11: 153–7

    Article  PubMed  CAS  Google Scholar 

  20. Orwoll ES. Androgen: basic biology and clinical implication. Calcif Tissue Int 2001; 69: 185–8

    Article  PubMed  CAS  Google Scholar 

  21. Hughes CL, Wall LL, Creasman WT. Reproductive hormone levels in gynaecologic oncology patients undergoing surgical castration after spontaneous menopause. Gynecol Oncol 1991; 40: 42–5

    Article  PubMed  Google Scholar 

  22. Stepan JJ, Lachman M, Zverina J, et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodelling. J Clin Endocrinol Metab 1989; 69: 523–7

    Article  PubMed  CAS  Google Scholar 

  23. Collinson MP, Tyrrel CJ, Hutton C. Osteoporosis occurring in two patients receiving LHRH analogues for carcinoma of the prostate. Calcif Tissue Int 1994; 54: 327–8

    Article  PubMed  CAS  Google Scholar 

  24. Daniell HW. Osteoporosis after orchiectomy for prostate cancer. J Urol 1997; 157: 439–44

    Article  PubMed  CAS  Google Scholar 

  25. Shaun A. McGrath G, Diamond T. Osteoporosis as a complication of orchiectomy in 2 elderly men with prostatic cancer. J Urol 1995; 154: 535–6

    Article  Google Scholar 

  26. Wei JT, Gross M, Jaffe CA, et al. Androgen deprivation therapy for prostate cancer results in significant loss of bone density. Urology 1999; 54: 607–11

    Article  PubMed  CAS  Google Scholar 

  27. Kiratli JB, Srinivas S, Perkash I, et al. Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer. Urology 2001; 57: 127–32

    Article  PubMed  CAS  Google Scholar 

  28. Stoch SA, Parker RA, Chen L. Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 2001; 86(6): 2787–91

    Article  PubMed  CAS  Google Scholar 

  29. Eriksson S, Eriksson A, Stege R, et al. Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogen. Calcif Tissue Int 1995; 57: 97–9

    Article  PubMed  CAS  Google Scholar 

  30. Daniell HW, Dunn SR, Ferguson DW, et al. Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol 2000; 163: 181–6

    Article  PubMed  CAS  Google Scholar 

  31. Diamond T, Campbell J, Bryant C, et al. The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy. Cancer 1998; 83(8): 1561–6

    Article  PubMed  CAS  Google Scholar 

  32. Maillefert JF, Sibilia J, Michel F, et al. Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma. J Urol 1999; 161: 1219–22

    Article  PubMed  CAS  Google Scholar 

  33. Berruti A, Dogliotti L, Terrone C, et al. Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in prostate cancer patients without apparent bone metastases given androgen deprivation therapy. J Urol 2002; 167: 2361–7

    Article  PubMed  Google Scholar 

  34. Smith MR, McGovern FJ, Fallon MA, et al. Low bone mineral density in hormone naïve-men with prostate carcinoma. Cancer 2001; 91: 2238–45

    Article  PubMed  CAS  Google Scholar 

  35. Daniell HW, Tam EW. Testicular atrophy in therapeutic orchiectomy specimens from men with prostate carcinoma: association with prior prostate bed irradiation and older age. Cancer 1998; 83: 1174–9

    Article  PubMed  CAS  Google Scholar 

  36. Hatano T, Oishi Y, Furuta A, et al. Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer. Br J Urol 2000; 86: 449–52

    Article  CAS  Google Scholar 

  37. Towsend MF, Sanders WH, Northway RO, et al. Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate cancer. Cancer 1997; 79: 545–50

    Article  Google Scholar 

  38. Oefelein MG, Ricchiuti V, Conrad W, et al. Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. J Urol 2001; 166: 1724–8

    Article  PubMed  CAS  Google Scholar 

  39. Jacobsen SJ, Goldberg J, Miles TP, et al. Hip fracture incidence among the old and the very old: a population based study of 745,435 cases. Am J Public Health 1990; 80: 871–3

    Article  PubMed  CAS  Google Scholar 

  40. Mauras N, Hayes V, Welch S, et al. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength and adiposity. J Clin Endocrinol Metab 1998; 83(6): 1886–92

    Article  PubMed  CAS  Google Scholar 

  41. Berruti A, Dogliotti L, Tucci M, et al. Metabolic bone disease induced by prostate cancer: rationale for the use of bis-phosphonates. J Urol 2001; 166(6): 2023–31

    Article  PubMed  CAS  Google Scholar 

  42. Berruti A, Piovesan A, Torta M, et al. Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension. Br J Cancer 1996; 73: 1581–7

    Article  PubMed  CAS  Google Scholar 

  43. Berruti A, Dogliotti L, Gorzegno G, et al. Differential patterns of bone turnover in relation to bone pain and disease extent in bone in cancer patients with skeletal metastases. Clin Chem 1999; 45: 1240–7

    PubMed  CAS  Google Scholar 

  44. Berruti A, Dogliotti L, Bitossi R, et al. Incidence of skeletal complications in bone metastatic prostate cancer patients with hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000; 164: 1248–53

    Article  PubMed  CAS  Google Scholar 

  45. Higano CS, Stephens C, Nelson P, et al. Prospective serial measurements of bone mineral density (BMD) in prostate cancer patients without bone metastases treated with intermittentandrogen suppression (IAS) [abstract]. Proc Am Soc Clin Oncol 1999; 18: 314a

    Google Scholar 

  46. Gluer CC. The use of bone densitometry in clinical practice. Bailliere’s Clin Endocrinol Metab 2000; 14: 195–211

    CAS  Google Scholar 

  47. Stepan JJ. Prediction of bone loss in postmenopausal women. Osteoporos Int 2000; 11 Suppl. 6: 66–76

    Google Scholar 

  48. Bilezikian JP, Panel Members. Optimal calcium intake: statement of the consensus development panel on optimal calcium intake. JAMA 1994; 272: 1942–8

    Article  Google Scholar 

  49. Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years or older. N Engl J Med 1997; 337: 670–6

    Article  PubMed  CAS  Google Scholar 

  50. Kanis JA, McKloskey EV, O’Doherty D. Treatment of Paget’s disease with the new bisphosphonates. In: Singer R, Wallach S, editors. Paget’s disease of bone: clinical assessment present and future therapy. New York: Elsevier, 1991: 112

    Google Scholar 

  51. Reginster JY, Lecart MP, Deroisy R, et al. Prevention of postmenopausal bone loss by tiludronate. Lancet 1989; II: 1469–71

    Article  Google Scholar 

  52. Ralston SH. Pathogenesis and management of cancer associated hypercalcemia. Cancer Surv 1994; 21: 179–96

    PubMed  CAS  Google Scholar 

  53. Berenson JR, Linchtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia study group. N Engl J Med 1996; 334: 488–93

    Article  PubMed  CAS  Google Scholar 

  54. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic metastases: protocol 19. Aredia breast cancer study group. N Engl J Med 1996; 335: 1785–91

    Article  PubMed  CAS  Google Scholar 

  55. Body JJ, Bartl R, Burckhardt P, et al. Current use of bisphosphonates in oncology. International bone and cancer study group. J Clin Oncol 1998; 16(12): 3890–9

    PubMed  CAS  Google Scholar 

  56. Dearnaley DP, Sydes MR, on behalf of the MRC PR05 collaborators. Preliminary evidence that oral clodronate delays symptomatic progression of bone metastases from prostate cancer: first results of the MRC Pr05 trial [abstract]. Proc Am Soc Clin Oncol 2001; 693: 174a

    Google Scholar 

  57. Saad F, Gleason DM, Murray R, et al. A randomized, placebo controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 1458–68

    Article  PubMed  CAS  Google Scholar 

  58. Fleisch H. Bisphosphonates: pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease. Drugs 1991; 42: 919–44

    Article  PubMed  CAS  Google Scholar 

  59. Degroen PC, Lubbe DF, Hisch LJ, et al. Esophagitis associated with the use of aledronate. N Engl J Med 1996; 335: 1016–21

    Article  CAS  Google Scholar 

  60. Reid IR. Pharmacological management of osteoporosis in postmenopausal women. Drugs Aging 1999; 15(5): 349–63

    Article  PubMed  CAS  Google Scholar 

  61. Orwoll E, Ettinger M, Weiss S, et al. Aledronate for the treatment of osteoporosis in men. N Engl J Med 2000; 343: 604–10

    Article  PubMed  CAS  Google Scholar 

  62. Gonnelli S, Cepollaro C, Montagnani A, et al. Aledronate treatment in men with primary osteoporosis: a 3-year longitudinal study [abstract F398]. J Bone Miner Res 2000; 15 Suppl. 1: 228

    Google Scholar 

  63. Clarke NW, McClure J, George NJ. The effects of orchidectomy on skeletal metabolism in metastatic prostate cancer. Scand J Urol Nephrol 1993; 27(4): 475–83

    Article  PubMed  CAS  Google Scholar 

  64. Diamond TH, Winters J, Smith A, et al. The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 2001; 92: 1444–50

    Article  PubMed  CAS  Google Scholar 

  65. Smith MR, McGovern FJ, Zietman AL. Pamidronate to prevent bone loss during androgen deprivation therapy for prostate cancer. N Engl J Med 2001; 345: 948–55

    Article  PubMed  CAS  Google Scholar 

  66. Cheer SM, Noble S. Zoledronic acid. Drugs 2001; 61(6): 799–805

    Article  PubMed  CAS  Google Scholar 

  67. Daniell HW. Osteoporosis due to androgen deprivation therapy in men with prostate cancer. Urology 2001; 58 Suppl. 2A: 101–7

    Article  PubMed  CAS  Google Scholar 

  68. Scherr D, Pitts WR, Vaughan Jr DE. Diethylstibesterol revisited: androgen deprivation osteoporosis and prostate cancer. J Urol 2002; 167: 535–8

    Article  PubMed  CAS  Google Scholar 

  69. Cox RL, Crawford DE. Estrogens in the treatment of prostate cancer. J Urol 1995; 154: 1991–8

    Article  PubMed  CAS  Google Scholar 

  70. Calero JA, Diaz-Curiel M, de La Pedra C. Bicalutamide (Casodex) treatment does not produce bone effects in male Wistar rats [abstract F034]. J Bone Miner Res 1999; 14 Suppl. 1: 220

    Google Scholar 

  71. Abrahamsson PA. Treatment of locally advanced prostate cancer: a new role for antiandrogen monotherapy? Eur Urol 2001; 39 Suppl. 1: 22–8

    Article  PubMed  CAS  Google Scholar 

  72. Chodak G, Sharifi R, Kasimis B, et al. Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma. Urology 1995; 46(6): 849–55

    Article  PubMed  CAS  Google Scholar 

  73. Iversen P, Tyrrell CJ, Kaisary AV, et al. Bicalutamide monotherapy compared with castration in patients with non-metastatic locally advanced prostate cancer: 6.3 years of follow-up. J Urol 2000; 164(5): 1579–82

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Alfredo Berruti, Luigi Dogliotti and Alberto Angeli are consultants for Novartis Company.

Author information

Authors and Affiliations

  1. Oncologia Medica, Azienda Ospedaliera San Luigi, Orbassano, Italy

    Alfredo Berruti, Marcello Tucci, Gabriella Gorzegno & Luigi Dogliotti

  2. Urologia, Azienda Ospedaliera San Luigi, Orbassano, Italy

    Carlo Terrone & Roberto M. Scarpa

  3. Medicina Interne, Azienda Ospedaliera San Luigi, Orbassano, Italy

    Alberto Angeli

Authors
  1. Alfredo Berruti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcello Tucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlo Terrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriella Gorzegno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto M. Scarpa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alberto Angeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luigi Dogliotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Berruti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berruti, A., Tucci, M., Terrone, C. et al. Background to and Management of Treatment-Related Bone Loss in Prostate Cancer. Drugs Aging 19, 899–910 (2002). https://doi.org/10.2165/00002512-200219120-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200219120-00002

Keywords

Search

Navigation