Contribution of androgen deprivation therapy to elevated osteoclast activity in men with metastatic prostate cancer.
OBJECTIVE
Biochemical markers of both osteoblast and osteoclast activity are elevated in men with osteoblastic metastases from prostate cancer. Androgen deprivation therapy (ADT), the mainstay of therapy for advanced prostate cancer, increases markers of osteoblast and osteoclast activity, even in the absence of bone metastases. Little is known about the relative contributions of ADT and skeletal metastases to elevated bone turnover in men with prostate cancer.


METHODS
To evaluate the relative contributions of ADT and skeletal metastases to osteoblast and osteoclast activity, we performed a cross-sectional study in three groups of men with advanced prostate cancer: (a) hormone-naïve men without bone metastases; (b) castrate men without bone metastases; and (c) castrate men with bone metastases. The primary study end points were serum levels of bone-specific alkaline phosphatase (BSAP), a marker of osteoblast activity, and N-telopeptide (NTX), a marker of osteoclast activity.


RESULTS
Serum levels of both BSAP and NTX were significantly higher in groups of castrate men (groups 2 and 3) than in hormone-naïve men (group 1; P < 0.01 for all comparisons). Among castrate men, serum BSAP was significantly higher in men with bone metastases than in men without bone metastases (P = 0.01). In contrast, serum levels of NTX were similar in groups 2 and 3 (P = 0.33).


CONCLUSIONS
The unintended effects of ADT on the skeleton are sufficient to explain increased osteoclast activity in castrate men with bone metastases. These results may have important implications for the optimal timing and schedule of osteoclast-targeted therapy in men with advanced prostate cancer.
Michaelson
M Dror
MD
Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. dmichaelson1@partners.org
Marujo
Rose M
RM
Smith
Matthew R
MR
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000726:Androgen Antagonists / Q000494:pharmacology*; D001842:Bone and Bones / Q000378:metabolism; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D011471:Prostatic Neoplasms / Q000628:therapy*
D000726:Androgen Antagonists; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000469:Alkaline Phosphatase