Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Edinburgh Clinical Trials Unit, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
J Bone Miner Res. 2017 Jun;32(6):1165-1173. doi: 10.1002/jbmr.3066. Epub 2017 Feb 8.
It has been suggested that normalization of bone turnover may improve clinical outcome in Paget's disease of bone (PDB) by preventing complications such as fractures and the development of osteoarthritis. Here we investigated the long-term effects of a treatment strategy that aimed to normalize bone turnover in PDB with that of symptomatic treatment. The study group comprised 502 subjects who were enrolled into a 3-year extension of the Paget's Disease: Randomized Trial of Intensive versus Symptomatic Management (PRISM) study. Intensive bisphosphonate therapy was continued in 270 of these subjects with the aim of normalizing bone turnover using zoledronic acid as the treatment of first choice. Symptomatic treatment continued in 232 subjects in whom bisphosphonates were only given for the treatment of bone pain. The primary outcome was fracture and secondary outcomes were orthopedic procedures, quality of life, and bone pain, adjusted for baseline characteristics. Serum total alkaline phosphatase (ALP) concentrations were significantly lower in the intensive group on entry to the study and the differences between groups increased as the study progressed. There were no clinically important differences in quality of life measures or bone pain between the treatment groups. Intensive treatment was associated with a nonsignificant increase in fracture risk (hazard ratio = 1.90; 95% CI, 0.91 to 3.98; p = 0.087), orthopedic procedures (1.81; 95% CI, 0.71 to 4.61; p = 0.214), and serious adverse events (relative risk 1.28; 95% CI, 0.96 to 1.42). We conclude that long-term intensive bisphosphonate therapy confers no clinical benefit over symptomatic therapy and is associated with a nonsignificant increase in the risk of fractures, orthopedic events, and serious adverse events. The results of this study suggest that in patients with established PDB, bisphosphonate therapy should focus on control of symptoms rather than suppression of bone turnover. © 2016 American Society for Bone and Mineral Research.
有人提出，通过预防骨折和骨关节炎等并发症，使骨骼代谢恢复正常可能会改善 Pagets 病（PDB）的临床预后。在这里，我们研究了旨在使 PDB 骨骼代谢恢复正常的治疗策略与对症治疗的长期效果。该研究组包含了 502 名参加 Pagets 病：强化与对症治疗随机试验（PRISM）研究 3 年扩展期的患者。270 名患者接受强化双磷酸盐治疗，使用唑来膦酸作为一线治疗药物，以达到骨骼代谢正常化的目的。232 名患者仅接受双磷酸盐治疗骨痛，作为对症治疗。主要结局为骨折，次要结局为矫形手术、生活质量和骨痛，调整了基线特征。在研究开始时，强化组的血清总碱性磷酸酶（ALP）浓度显著较低，随着研究的进展，两组之间的差异增大。在治疗组之间，生活质量测量或骨痛没有临床意义上的差异。强化治疗与骨折风险增加无显著相关性（危险比=1.90；95%置信区间，0.91 至 3.98；p=0.087），与矫形手术（1.81；95%置信区间，0.71 至 4.61；p=0.214）和严重不良事件（相对风险 1.28；95%置信区间，0.96 至 1.42）无关。我们的结论是，长期强化双磷酸盐治疗与对症治疗相比没有带来临床益处，与骨折、矫形手术和严重不良事件风险增加无显著相关性。这项研究的结果表明，对于已确诊的 PDB 患者，双磷酸盐治疗应侧重于控制症状，而不是抑制骨骼代谢。© 2016 美国骨矿研究学会。
