title: Long-term dynamics of bone mineral density during intermittent androgen deprivation for men with nonmetastatic, hormone-sensitive prostate cancer.
abstract: OBJECTIVE
  To investigate changes in bone mineral density (BMD) and fracture risk in men who received intermittent androgen deprivation (IAD) for nonmetastatic, hormone-sensitive prostate cancer.
  
  
  METHODS
  Men with prostate cancer who lacked radiographically detectable metastases were treated in a prospective trial of IAD. After 9 months of treatment with leuprolide and flutamide, androgen deprivation therapy (ADT) was stopped until prostate-specific antigen reached a threshold (1 ng/mL for radical prostatectomy; 4 ng/mL for radiation or primary ADT) for a new cycle. Dual-energy x-ray absorptiometry (DXA) scans were performed before starting ADT and subsequently with each change in therapy. At least two consecutive DXA scans were required for this analysis. Computed tomography, bone scintigraphy, and lumbar spine x-rays were performed at the beginning and end of each treatment period.
  
  
  RESULTS
  Fifty-six of 100 patients met criteria for this analysis. The median age at study entry was 64.5 years (range, 49.8 to 80.9 years). The average percentage change in BMD during the first on-treatment period was -3.4% (P < .001) for the spine and -1.2% (P = .001) for the left hip. During the first off-treatment period (median, 37.4 weeks; range, 13.4 weeks to 8.7+ years), BMD recovery at the spine was significant, with an average percentage change of +1.4% (P = .002). Subsequent periods had heterogeneous changes of BMD without significant average changes. After a median of 5.5 years (range, 1.1 to 13.8+) years on trial, one patient (1.8%) had a compression fracture associated with trauma.
  
  
  CONCLUSIONS
  Patients experienced the greatest average change in BMD during early treatment periods of IAD with a smaller average change thereafter. Fractures were rare.
authors.affiliation: University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA. thigano@u.washington.edu
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Yu
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Kuo
authors.forename: Roman
authors.initials: R
authors.lastname: Gulati
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.forename: Teresa E
authors.initials: TE
authors.lastname: Gambol
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Hall
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Jiang
authors.forename: Peggy
authors.initials: P
authors.lastname: Pitzel
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000473:pathology; D004334:Drug Administration Schedule; D005485:Flutamide / Q000008:administration & dosage; D050723:Fractures, Bone / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D016729:Leuprolide