Saad Fred, Markus Richard, Goessl Carsten
University of Montreal, Montreal, Quebec, Canada.
BJU Int. 2008 May;101(9):1071-5. doi: 10.1111/j.1464-410X.2007.07364.x. Epub 2007 Dec 5.
Newly formed bone in the typically osteoblastic bone metastases from prostate cancer shows characteristics of woven bone, e.g. marked defects in mineralization and microstructure. Adding to the reduced mechanical strength of prostate cancer bone metastasis is an increasingly recognized osteolytic component. The existence of osteoclasts in osteoblastic bone metastases and concomitant increases in urine or serum markers for bone resorption are reported in affected patients. Pathologically increased osteoclastic bone resorption is a key mediator of the clinical complications from bone metastases, among them fractures, spinal cord compression and bone pain. The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) pathway has been identified as the main driving force for osteoclastogenesis and resulting bone resorption. Emerging data indicate that bone marrow-derived RANKL might also constitute a chemoattractant factor for RANK-expressing tumour cells that is likely to contribute to the pathogenesis of bone metastases, including those arising from prostate cancer. Cumulative evidence supports RANKL inhibition as a therapeutic goal for the treatment and prevention of bone metastases from prostate cancer.
在前列腺癌典型的成骨细胞性骨转移中，新形成的骨呈现出编织骨的特征，例如矿化和微观结构存在明显缺陷。除了前列腺癌骨转移机械强度降低外，一种越来越被认可的溶骨成分也存在。在受影响的患者中，已报道在成骨细胞性骨转移中有破骨细胞存在，并且尿液或血清中的骨吸收标志物也随之增加。病理上破骨细胞性骨吸收增加是骨转移临床并发症的关键介质，其中包括骨折、脊髓压迫和骨痛。核因子（NF）-κB 受体活化因子配体（RANKL）途径已被确定为破骨细胞生成及由此导致骨吸收的主要驱动力。新出现的数据表明，骨髓来源的 RANKL 可能也是表达 RANK 的肿瘤细胞的趋化因子，这可能有助于包括前列腺癌骨转移在内的骨转移发病机制。越来越多的证据支持将抑制 RANKL 作为治疗和预防前列腺癌骨转移的治疗目标。
