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Bone loss associated with the use of LHRH agonists in prostate cancer

Prostate Cancer and Prostatic Diseases volume 4, pages 161–166 (2001)Cite this article

Abstract

Hypogonadism is a recognised cause of osteoporosis in men. When patients with advanced prostate cancer are treated with luteinising hormone releasing hormone (LHRH) agonist analogues their circulating testosterone levels decline and these patients may develop fractures.

We have undertaken a cross-sectional study on a cohort of patients treated with goserelin (n=41) and compared their bone density and bone turnover with patients with prostate cancer not on goserelin and elderly patients living in the community.

There was no difference in bone density between the patients on treatment and those living in the community and there was a similar incidence of osteoporosis (50 and 42%, respectively). The bone marker measurements were higher in the treated patients: urine N-telopeptide (NTX) 80.1 (9) (mean (s.e.)) BCE/mmol, compared to 30.1 (2.9), P<0.001 in elderly patients; and bone alkaline phosphatase 41.9 (6.1) u/l in treated patients and 20.7 (1.5) in untreated prostate cancer patients, P<0.002. Patients on treatment with radionuclide scan evidence of metastases did not have higher bone marker values than those with negative scans.

As increased bone turnover and low bone density are associated with enhanced risk of osteoporotic fractures, we suggest that patients on LHRH agonist analogues should receive advice and possibly anti-bone resorptive treatment with bisphosphonates to prevent further bone loss and fractures.

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References

  1. Orwell ES, Klein RF Osteoporosis in men. Endocrine Rev 1995 16 87–116

    Article  Google Scholar 

  2. Scane AC et al. Case control study of the pathogenesis and sequelae of symptomatic vertebral fractures in men. Osteoporosis Int 1999 9 91–97

    Article  CAS  Google Scholar 

  3. Vanderschueren D, Boonen S, Bouillon R Action of androgens versus oestrogens in male skeletal homeostasis. Bone 1998 23 391–394

    Article  CAS  Google Scholar 

  4. Stepan JJ et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodelling. J Clin Endocrinol Metab 1989 69 523–527

    Article  CAS  Google Scholar 

  5. Goldray D et al. Decreased bone mineral density in elderly men treated with the gonadotrophin-releasing hormone agonist decapeptyl (D-trp6-GnRH). J Clin Endocrinol Metab 1993 76 288–290

    CAS  PubMed  Google Scholar 

  6. Guo CY, Jones H, Eastell H Treatment of isolated hypogonadatropic hypogonadism effect on bone mineral density and bone turnover. J Clin Endocrinol Metab 1997 82 658–665

    Article  CAS  Google Scholar 

  7. Katznelson L et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996 81 4358–4365

    CAS  PubMed  Google Scholar 

  8. Chamerlain J, Melia J, Moss S, Brown J Health Technology Assessment Panel of the NHS Executive Report on the diagnosis, management, treatment and costs of prostate cancer in England and Wales. Br J Urol 1997 79 (Suppl 3): 1–32

    Google Scholar 

  9. Kaisary AV, Tyrrell CJ, Peeling WR, Griffiths K Comparison of LHRH analogue (Zoladex) with orchidectomy in patients with metastatic prostatic carcinoma. Br J Urol 1997 67 502–508

    Article  Google Scholar 

  10. Daniell HW Osteoporosis after orchidectomy for prostate cancer. J Urol 1997 157 439–444

    Article  CAS  Google Scholar 

  11. Hatano T et al. Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer. Br J Urol Int 2000 86 449–452

    Article  CAS  Google Scholar 

  12. Fairney A, De Vooght K, Venema M, Thomas E Evaluation of the Osteometer DTX 200, Durrent Research in the Osteoporosis and Bone Mineral Measurement V. In: Ring EFJ, Elvins DM, Bhalla AK (eds). Current Research in Osteoporosis and Bone Mineral Measurement V British Institute of Radiology: London 1998 30–31

    Google Scholar 

  13. World Health Organisation Assessment of fracture risk and its application to screening for post menopausal osteoporosis. Technical Report Series 843. WHO: Geneva 1994

  14. Delmas PD et al. Immunoassay of pyridinoline cross link excretion in normal adults and in Paget's disease. J Bone Miner Res 1993 8 643–648

    Article  CAS  Google Scholar 

  15. Orwell ES et al. Collagen N telopeptide excretion in men and the effects of age and intra subject variability. J Clin Endocrinol Metab 1998 83 3930–3935

    Google Scholar 

  16. Schneider DL, Barrett-Connor EL Urinary N telopeptide levels discriminate normal osteopenic and osteoporotic bone mineral density. Arch Intern Med 1997 157 1241–1245

    Article  CAS  Google Scholar 

  17. Townsend MF, Sanders WH, Northway RO, Graham SD Bone fractures associated with luteinizing hormone-releasing agonists used in the treatment of prostate carcinoma. Cancer 1997 79 545–550

    Article  CAS  Google Scholar 

  18. Daniell HW et al. Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol 2000 163 181–186

    Article  CAS  Google Scholar 

  19. Maillefert JF et al. Bone mineral density in men treated with synthetic gonadotrophin releasing hormone agonists for prostatic carcinoma. J Urol 1999 161 1219–1222

    Article  CAS  Google Scholar 

  20. Genant HK et al. Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting bone loss after oopherectomy. Ann Intern Med 1982 97 699–705

    Article  CAS  Google Scholar 

  21. Mazess RB et al. Influence of age and body weight on spine and femur bone mineral density in US white men. J Bone Miner Res 1990 5 645–652

    Article  CAS  Google Scholar 

  22. Need AG et al. Effect of physical activity on femoral bone density in men. Br Med J 1995 310 1501–1502

    Article  CAS  Google Scholar 

  23. Johansen JS et al. The effect of a gonadtrophin-releasing hormone agonist analog (Nafarelin) on bone metabolism. J Clin Endocrinol Metab 1998 67 701–706

    Article  Google Scholar 

  24. Garnero P, Sornay-Render E, Chapuy MC, Delmas PD Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996 11 337–349

    Article  CAS  Google Scholar 

  25. Nguyen-Pamart M et al. The diagnostic value of urinary crosslaps and serum alkaline phosphatase in patients with prostate cancer. Br J Urol 1997 80 452–455

    Article  CAS  Google Scholar 

  26. Garnero P et al. Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer 2000 82 858–864

    Article  CAS  Google Scholar 

  27. Clarke NW, McClure J, George NJR Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol 1991 68 74–80

    Article  CAS  Google Scholar 

  28. Stepan JJ, Pospichal J, Presl J, Pacovsky V Bone loss and biochemical indices of bone remodelling in surgically-induced postmenopausal women. Bone 1987 8 279–284

    Article  CAS  Google Scholar 

  29. Uebelhart D et al. Effect of menopause and hormone replacement therapy on the urinary excretion of pyridium cross-links. J Clin Endocrinol Metab 1991 72 367–373

    Article  CAS  Google Scholar 

  30. Hansen MA, Overgaard K, Ris BJ, Christiansen C Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12-year study. Br Med J 1991 303 961–964

    Article  CAS  Google Scholar 

  31. Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD Markers of bone turnover predict postmenopausal forearm bone loss over four years: the OFELY study. J Bone Miner Res 1999 14 1614–1621

    Article  CAS  Google Scholar 

  32. Delmas PD et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporosis Int 2000 11 (Suppl 6):2–17

    Google Scholar 

  33. Black DM et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996 348 1535–1541

    Article  CAS  Google Scholar 

  34. Torgerson DJ Examples of treatment groups for fracture prevention. Osteoporosis Rev 1999 7 1–4

    Google Scholar 

  35. Boissier S et al. Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 2000 60 2949–2954

    CAS  PubMed  Google Scholar 

  36. Ziotta AR, Schulman CC Can survival be prolonged for patients with hormone resistant prostate cancer? Lancet 2001 357 326–327

    Article  Google Scholar 

  37. Mussolino ME et al. Risk factors for hip fracture in white men: the NHANES I epidemiological follow-up study. J Bone Miner Res 1998 13 918–924

    Article  CAS  Google Scholar 

  38. Orwell E et al. Alendronate for the treatment of osteoporosis in men. New Engl J Med 2000 343 604–610

    Article  Google Scholar 

  39. Mundy GR, Yoneda T Bisphosphonates as anticancer drugs. New Engl J Med 1998 339 398–400

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Merck Sharp and Dohme for sponsorship of the bone density measurements and to the Urology Department at Northwick Park Hospital for allowing us to include their patients in our study.

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Authors and Affiliations

  1. Department of Urology, St Mary's NHS Trust London, UK

    JL Peters, A Patel, JJ Webster, JA Vale & RON Witherow

  2. Department of Endocrinology and Metabolic Medicine, Imperial College School of Medicine, London, UK

    A Fairney, P Kyd & S Rogers

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  1. JL Peters
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  2. A Fairney
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Peters, J., Fairney, A., Kyd, P. et al. Bone loss associated with the use of LHRH agonists in prostate cancer. Prostate Cancer Prostatic Dis 4, 161–166 (2001). https://doi.org/10.1038/sj.pcan.4500520

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