Department of Cardiology, Nephrology and Endocrinology, North Zealand Hospital, Hillerød, Dyrehavevej 29, 3400, Hillerød, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Osteoporos Int. 2017 Oct;28(10):2921-2928. doi: 10.1007/s00198-017-4132-y. Epub 2017 Jun 29.
Osteonecrosis of the jaw (ONJ) is rare (2.53/10,000 person-years) among alendronate users, but long-term and compliant use are associated with an increased risk of surgically treated ONJ. Risk of surgically treated ONJ is higher in patients with rheumatoid diseases and use of proton pump inhibitors.
ONJ is a rare event in users of oral bisphosphonates. Our aims were to evaluate if the risk of surgically treated ONJ increases with longer or more compliant treatment with alendronate for osteoporosis and to identify risk factors for surgically treated ONJ.
Open nationwide register-based cohort study containing one nested case-control study. Patients were treatment-naïve incident users of alendronate 1996-2007 in Denmark, both genders, aged 50-94 at the time of beginning treatment (N = 61,990). Participants were followed to 31 December 2013.
Over a mean of 6.8 years, 107 patients received surgery for ONJ or related conditions corresponding to an incidence rate of 2.53 (95% confidence interval (CI) 2.08 to 3.05) per 10,000 patient years. Recent use was associated with an adjusted odds ratio (OR) 4.13 (95% CI 1.94 to 8.79) compared to past use. Similarly, adherent users (medication possession ratio (MPR) >50%) were at two to threefold increased risk of ONJ compared to low adherence (MPR <50%), and long-term (>5 years) use was related with higher risk (adjusted OR 2.31 (95% CI (1.14 to 4.67)) than shorter-term use. History of rheumatoid disorders and use of proton pump inhibitors were independently associated with surgically treated ONJ.
Our data suggest that recent, long-term, and compliant uses of alendronate are associated with an increased risk of surgically treated ONJ. Nevertheless, the rates remain low, even in long-term adherent users. ONJ risk appears higher in patients with conditions likely to indirectly affect the oral mucosa.
在阿伦膦酸盐使用者中，颌骨坏死（ONJ）很少见（2.53/10000 人年），但长期和依从性治疗与手术治疗的 ONJ 风险增加有关。患有类风湿性疾病和使用质子泵抑制剂的患者发生手术治疗的 ONJ 风险更高。
ONJ 是口服双膦酸盐使用者中罕见的事件。我们的目的是评估阿伦膦酸盐治疗骨质疏松症的时间更长或更依从性是否会增加手术治疗的 ONJ 风险，并确定手术治疗的 ONJ 的危险因素。
这是一项全国范围内的基于登记的队列研究，其中包含一项嵌套病例对照研究。患者为 1996-2007 年丹麦首次使用阿伦膦酸盐治疗的骨质疏松症的治疗初治患者，男女不限，治疗开始时年龄为 50-94 岁（N=61990）。参与者随访至 2013 年 12 月 31 日。
在平均 6.8 年的时间内，107 例患者因 ONJ 或相关疾病接受手术治疗，发生率为每 10000 人年 2.53（95%置信区间[CI]2.08 至 3.05）。与过去使用相比，近期使用的调整后比值比（OR）为 4.13（95%CI 1.94 至 8.79）。同样，与低依从性（药物使用比例[MPR] <50%）相比，依从性好（MPR>50%）的患者发生 ONJ 的风险增加了两到三倍，而长期（>5 年）使用与更高的风险相关（调整后的 OR 2.31（95%CI 1.14 至 4.67））与短期使用相比。类风湿性疾病史和质子泵抑制剂的使用与手术治疗的 ONJ 独立相关。
我们的数据表明，近期、长期和依从性使用阿伦膦酸盐与手术治疗的 ONJ 风险增加有关。尽管如此，即使在长期依从性好的患者中，发生率仍然较低。ONJ 风险似乎在可能间接影响口腔黏膜的疾病患者中更高。
