Siris Ethel S, Lyles Kenneth W, Singer Frederick R, Meunier Pierce J
Department of Medicine, Columbia University Medical Center, New York Presbyterian Hospital, New York, New York, USA.
J Bone Miner Res. 2006 Dec;21 Suppl 2:P94-8. doi: 10.1359/jbmr.06s218.
Treatment with a potent bisphosphonate is indicated in patients with Paget's disease who have symptoms likely to respond to reduced bone turnover at pagetic sites. In asymptomatic patients with active disease at sites susceptible to local progression and late complications, treatment is also recommended. Biochemical remission is achievable in a majority of patients with pamidronate, alendronate, risedronate, or zoledronic acid. Indications for medical treatment of active Paget's disease of bone include symptoms referable to sites of the disease such as bone pain, joint pain, and neurological complications; elective surgery at an active pagetic site to reduce intraoperative blood loss from highly vascular bone; management of rare instances of immobilization hypercalcemia with polyostotic disease; and presence of disease activity in asymptomatic patients at sites at risk for future complications to limit progression and possibly lower that risk. The treatment of choice is a potent nitrogen-containing bisphosphonate, including oral alendronate or risedronate or intravenous pamidronate or zoledronic acid. Etidronate and tiludronate are less potent and are second-line choices. Recent data with zoledronic acid indicate that a single infusion of 5 mg is associated with normalization of serum alkaline phosphatase in 89% of patients and a prolonged biochemical remission, making it the most effective therapy available to date. Side effect profiles with alendronate and risedronate include esophageal irritation in a minority of patients. Intravenous pamidronate and zoledronic acid may induce an acute phase reaction with fever and flu-like symptoms with the first dose, primarily in patients who are treatment naïve to nitrogen-containing bisphosphonates. Calcium and vitamin D repletion are mandatory with these potent anti-osteoclast therapies to avoid hypocalcemia. Acquired resistance to etidronate and pamidronate has been reported in some patients, leading to lesser reductions in bone turnover and shorter periods of remission, but substitution with a different bisphosphonate provides a more robust response. It is not known whether resistance to other bisphosphonates in Paget's disease occurs.
对于患有佩吉特病且症状可能因减少病变部位骨转换而缓解的患者，建议使用强效双膦酸盐进行治疗。对于无症状但病变部位处于易发生局部进展和晚期并发症的活跃期患者，也推荐进行治疗。大多数使用帕米膦酸盐、阿仑膦酸盐、利塞膦酸盐或唑来膦酸治疗的患者可实现生化缓解。活动性骨佩吉特病的药物治疗指征包括与疾病部位相关的症状，如骨痛、关节痛和神经并发症；在活跃的病变部位进行择期手术以减少高血运骨的术中失血；治疗罕见的多骨型疾病固定性高钙血症病例；以及无症状患者病变部位存在疾病活动，这些部位有发生未来并发症的风险，以限制疾病进展并可能降低该风险。治疗的首选是强效含氮双膦酸盐，包括口服阿仑膦酸盐或利塞膦酸盐或静脉注射帕米膦酸盐或唑来膦酸。依替膦酸盐和替鲁膦酸盐效力较弱，为二线选择。唑来膦酸的最新数据表明，单次输注5毫克可使89%的患者血清碱性磷酸酶恢复正常，并实现生化缓解期延长，使其成为迄今为止最有效的治疗方法。阿仑膦酸盐和利塞膦酸盐的副作用包括少数患者出现食管刺激。静脉注射帕米膦酸盐和唑来膦酸可能在首次给药时引发急性期反应，伴有发热和流感样症状，主要发生在初次接受含氮双膦酸盐治疗的患者中。使用这些强效抗破骨细胞疗法时必须补充钙和维生素D以避免低钙血症。一些患者已报告对依替膦酸盐和帕米膦酸盐产生获得性耐药，导致骨转换降低幅度较小且缓解期较短，但换用不同的双膦酸盐可产生更强的反应。尚不清楚佩吉特病患者是否会对其他双膦酸盐产生耐药性。
