Ludwig Boltzmann Cluster of Translational of Oncology, Nussdorfer Strasse 64, Vienna A-1090, Austria.
Cancers (Basel). 2011 Sep 15;3(3):3601-9. doi: 10.3390/cancers3033601.
Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.
间歇性雄激素抑制（IAS）疗法通过在雄激素抑制（AS）和治疗停止之间交替循环，试图维持肿瘤细胞的激素依赖性，直到达到一定的前列腺特异性抗原（PSA）阈值。与标准的连续雄激素抑制（CAS）疗法相比，预计副作用会减少。本研究通过测定血清前胶原 I N 端肽（PINP）来检查 IAS 对骨代谢的影响，PINP 是胶原合成的生化标志物。研究了 58 例前列腺癌≥pT2 期患者的 105 个治疗周期，每月间隔评估睾酮、PSA 和 PINP 水平。在持续长达九个月的 AS 期间，PSA 水平可逆性降低，表明前列腺肿瘤发生凋亡性消退。在 AS 期间的最后一个月 PINP 增加，并在治疗停止期间达到峰值。在接下来的两个周期中，PINP 也呈现出类似的模式，只是在治疗停止的第一个月，由于胶原合成中断，PINP 水平较低。因此，血清 PINP 浓度的测量表明，在接受 AS 治疗超过 6 个月后，骨基质合成增加，这种情况一直持续到第一个治疗停止阶段，随后每个阶段都会出现中断。总之，在接受 IAS 治疗的患者中，在治疗停止期间，骨基质胶原的合成增加，而降解减少。尽管很难确定骨基质转换与骨折风险之间的直接关系，但 IAS 治疗前列腺肿瘤的生化进展预计会减少老年男性的骨质疏松症，这些男性经常处于骨折的高风险中，这代表了非常适合接受这种治疗的患者群体。
