Hosking David, Lyles Kenneth, Brown Jacques P, Fraser William D, Miller Paul, Curiel Manuel Diaz, Devogelaer Jean-Pierre, Hooper Michael, Su Guoqin, Zelenakas Ken, Pak Judy, Fashola Taiwo, Saidi Youssef, Eriksen Erik Fink, Reid Ian R
City Hospital, Nottingham, UK.
J Bone Miner Res. 2007 Jan;22(1):142-8. doi: 10.1359/jbmr.061001.
A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy.
Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease.
This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion.
ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers.
ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.
单次静脉输注5毫克唑来膦酸可使大多数佩吉特病患者的骨转换生化指标恢复至参考范围，并维持生化缓解至少2年。这种效果在很大程度上与治疗前的疾病活动度和先前的双膦酸盐治疗无关。
唑来膦酸（ZOL）是一种强效双膦酸盐，可快速、完全控制佩吉特病增加的骨转换。长期控制疾病活动是治疗的一个重要目标，希望这能降低诸如畸形、骨折和退行性关节疾病等并发症的风险。
本研究比较了静脉输注15分钟给予5毫克ZOL与口服利塞膦酸钠（RIS）每日30毫克，持续60天维持骨转换长期控制的能力。在延长期研究期间未给予双膦酸盐。所有达到治疗反应的患者（n = 296）均符合纳入标准，治疗反应定义为总碱性磷酸酶（总ALP）超过参考范围中点的过量值恢复正常或降低>75%。
ZOL将总ALP平均水平维持在参考范围中间，而接受利塞膦酸钠治疗的患者从治疗后6个月时间点开始总ALP呈线性增加。两种治疗方法在治疗后6个月最低点和24个月总ALP之间均呈线性关系。RIS的关系向上偏移，表明对于给定的治疗后生化活动水平，骨转换随时间增加。这与接受ZOL治疗的患者形成对比，在这18个月的延长期内总ALP通常保持不变。其他骨转换标志物也观察到类似的反应模式。
从治疗开始24个月内，ZOL可将骨转换维持在参考范围内。长期并发症的发生率和严重程度的降低可能需要多年持续使骨转换正常化，而现在使用ZOL这似乎是一个现实的可能性。
