Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer.
BACKGROUND
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.


METHODS
We conducted a 12-month prospective study at an academic medical center.


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


METHODS
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.
Greenspan
Susan L
SL
Osteoporosis Prevention and Treatment Center, University of Pittsburgh, Kaufmann Medical Building, Suite 1110, 3471 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3221, USA. griffithsd@msx.dept-med.pitt.edu
Coates
Penelope
P
Sereika
Susan M
SM
Nelson
Joel B
JB
Trump
Donald L
DL
Resnick
Neil M
NM
D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy / Q000009:adverse effects*; D010012:Osteogenesis / Q000187:drug effects; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery / Q000628:therapy*; D013997:Time Factors
D000726:Androgen Antagonists; D015415:Biomarkers; D007987:Gonadotropin-Releasing Hormone