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Bone Loss after Initiation of Androgen Deprivation Therapy in Patients with Prostate Cancer

Osteoporosis Prevention and Treatment Center (S.L.G., P.C.) and Division of Geriatric Medicine (S.L.G., N.M.R.), Department of Medicine; Departments of Health and Community Systems, Biostatistics, and Epidemiology (S.M.S.); and Department of Urology (J.B.N.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Roswell Cancer Center (D.L.T.), Buffalo, New York 14263

Address all correspondence and requests for reprints to: Susan L. Greenspan, M.D., Osteoporosis Prevention and Treatment Center, University of Pittsburgh, Kaufmann Medical Building, Suite 1110, 3471 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3221. E-mail: griffithsd{at}msx.dept-med.pitt.edu.

Context: Although androgen deprivation therapy (ADT) for prostate cancer is associated with bone loss, little is known about when this bone loss occurs.

Objective: We postulated that men on ADT would experience the greatest bone loss acutely after initiation of ADT.

Design and Setting: We conducted a 12-month prospective study at an academic medical center.

Patients or Other Participants: We studied 152 men with prostate cancer (30 with acute ADT, <6 months; 50 with chronic ADT, 6 months; and 72 with no ADT) and 43 healthy age-matched controls.

Main Outcome Measures: We assessed bone mineral density (BMD) of the hip, wrist, total body, and spine; body composition; and markers of bone turnover.

Results: After 12 months, men receiving acute ADT had a significant reduction in BMD of 2.5 ± 0.6% at the total hip, 2.4 ± 1.0% at the trochanter, 2.6 ± 0.5% at the total radius, 3.3 ± 0.5% at the total body, and 4.0 ± 1.5% at the posteroanterior spine (all P < 0.05). Men with chronic ADT had a 2.0 ± 0.6% reduction in BMD at the total radius (P < 0.05). Healthy controls and men with prostate cancer not receiving ADT had no significant reduction in BMD. Both use and duration of ADT were associated with change in bone mass at the hip (P < 0.05). Men receiving acute ADT had a 10.4 ± 1.7% increase in total body fat and a 3.5 ± 0.5% reduction in total body lean mass at 12 months, whereas body composition did not change in men with prostate cancer on chronic ADT or in healthy controls (P < 0.05). Markers of bone formation and resorption were elevated in men receiving acute ADT after 6 and 12 months compared with the other men with prostate cancer and controls (P < 0.05). Men in the highest tertile of bone turnover markers at 6 months had the greatest loss of bone density at 12 months.

Conclusions: Men with prostate cancer who are initiating ADT have a 5- to 10-fold increased loss of bone density at multiple skeletal sites compared with either healthy controls or men with prostate cancer who are not on ADT, placing them at increased risk of fracture. Bone loss is maximal in the first year after initiation of ADT, suggesting initiation of early preventive therapy.

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