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.
BACKGROUND
Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy.


METHODS
Twelve consecutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-releasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6-12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine BMD was measured by spinal quantitative computed tomography (QCT) and femoral neck BMD by dual energy X-ray absorptiometry (DXA).


RESULTS
Combined androgen blockade resulted in all men achieving serum free testosterone concentrations of <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates increased significantly (P < 0.01, respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93 mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94 g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P < 0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101 mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic etidronate therapy). Significant increases in BMD also were observed in the femoral neck and Ward's triangle.


CONCLUSIONS
Androgen receptor blocking agents have an established role in the treatment of disseminated prostate carcinoma. However, combined androgen blockade in elderly men with disseminated prostate carcinoma results in high bone turnover with significant cancellous bone loss. The results of this study show that adjuvant therapy with intermittent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures.
Diamond
T
T
Metabolic Bone Unit, St. George Hospital, Kogarah, Sydney, Australia.
Campbell
J
J
Bryant
C
C
Lynch
W
W
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000652:urine; D000726:Androgen Antagonists / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D004334:Drug Administration Schedule; D012968:Etidronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005272:Femur Neck / Q000473:pathology; D005485:Flutamide / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D013739:Testosterone / Q000097:blood; D014057:Tomography, X-Ray Computed; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D000596:Amino Acids; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D010281:Parathyroid Hormone; D017273:Goserelin; D015675:Osteocalcin; D014807:Vitamin D; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005485:Flutamide; C036020:deoxypyridinoline; C104450:25-hydroxyvitamin D; D017430:Prostate-Specific Antigen; D012968:Etidronic Acid; D002118:Calcium