Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk.


  • 影响因子:3.40
  • DOI:10.1097/MLR.0000000000001294
  • 作者列表:"Curtis JR","Saag KG","Arora T","Wright NC","Yun H","Daigle S","Matthews R","Delzell E
  • 发表时间:2020-05-01

BACKGROUND:Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES:We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN:Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS:Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES:Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS:Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION:Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.


背景: 治疗几年后停用双膦酸盐 (BP) 或 “药物假日” 越来越常见。然而,药物假期时间与未来骨折风险的相关性尚不清楚。 目的: 我们在接受长期BP治疗的妇女中评估了骨折率与各种药物假期的关系。 研究设计: 使用美国医疗保险数据的观察性队列研究 2006-2016。采用发病率 (IRs) 和Cox比例风险模型评价控制潜在混杂因素的率和调整风险比 (ahr)。 对象: 参加按服务付费医疗保险的 65 岁及以上女性,坚持阿仑膦酸钠、利塞膦酸钠或唑来膦酸钠 ≥ 3 年 (≥ 80%)。 措施: 髋部、肱骨、前臂远端、临床椎体骨折。 结果: 在 81,427 名符合条件的女性中,观察到的中位数 (四分位距) 为 4.0 (2.5,5.3) 年,28% 的女性接受了药物假期。在阿仑膦酸钠队列 (总体为 73%) 中,停用BP> 2 年的女性髋部骨折的IR为 13.2/1000 人年。与继续治疗 (IR = 1.3,参考) 相比,风险增加 (aHR = 1.1,1.4-8.8)。肱骨骨折停药> 2 年 (aHR = 1.3,1.1-1.66) 和临床椎体骨折停药> 2 年 (aHR = 1.2,1.1-1.4) 的发生率升高。利塞膦酸钠、唑来膦酸钠和伊班膦酸钠治疗髋部和临床椎体骨折的结果相似。 结论: 停用阿仑膦酸钠超过 2 年与髋部、肱骨和临床椎体骨折风险增加相关。



作者列表:["Denadai R","Seo HJ","Lo LJ"]

METHODS:BACKGROUND:The anterior oronasal fistulae neighboring the alveolar cleft could persist or reappear after the alveolar reconstruction with cancellous bone grafting. The persistent symptomatic anterior oronasal fistulae need to be repaired, but surgery remains a challenge in cleft care. Surprisingly, this issue has rarely been reported in the literature. The purpose of this long-term study was to report a single surgeon experience with a therapeutic protocol for persistent symptomatic anterior oronasal fistula repair. METHODS:This is a retrospective study of consecutive patients with Veau type III and IV clefts and persistent symptomatic anterior oronasal fistulae managed according to a therapeutic protocol from 1997 to 2018. Depending on fistula size, patients were treated with local flaps associated with an interpositional graft or two-stage tongue flaps (small/medium or large fistulae, respectively). The surgical outcomes were classified as "good" (complete fistula closure with no symptoms), "fair" (asymptomatic narrow fistula remained), or "poor" (failure with persistent symptoms). RESULTS:Forty-four patients with persistent symptomatic anterior oronasal fistulae were reconstructed with local flaps associated with interpositional fascia or dermal fat grafting (52.3%) or two-stage tongue flaps (47.7%). Most of patients (93.2%) presented "good" outcomes, ranging from 87% to 100% (local and tongue flaps, respectively). Three (6.8%) patients presented symptomatic residual fistula ("poor" outcomes). CONCLUSIONS:For the repair of persistent symptomatic anterior oronasal fistulae, this therapeutic protocol provided satisfactory outcome with low fistula recurrence rate.

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作者列表:["Cleary B","Loane M","Addor MC","Barisic I","de Walle HEK","Matias Dias C","Gatt M","Klungsoyr K","McDonnell B","Neville A","Pierini A","Rissmann A","Tucker DF","Zurriaga O","Dolk H"]

METHODS:OBJECTIVE:Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS. DESIGN/SETTING:This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011. PATIENTS:Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview. RESULTS:Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2). CONCLUSIONS:These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.

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作者列表:["Jahanbin A","Eslami N","Torkamanzadeh N"]

METHODS::Orthopedic treatment to improve deficient maxillary growth of cleft lip and palate patients is an important part of treatment. The success of this treatment is strongly dependent on the time of initiation of therapy. There has been a large controversy in the available literature regarding the skeletal age of these patients. The aim of the present study was to compare the skeletal age of cleft lip and palate patients with normal individuals.37 unilateral and 14 bilateral cleft lip and palate patients and 47 healthy individuals participated in this cross-sectional study. The patients were classified into 8 to 10 and 11 to 14-year-old individuals. Cervical vertebral maturational stage of participants was evaluated in the lateral cephalometry. The skeletal age of cleft lip and palate patients was compared with normal controls. Chi-square was used for statistical analysis. There was not a significant difference in the skeletal developmental stage of unilateral and bilateral cleft compared to their normal peers according to their age and sex. Also, significant difference in skeletal maturational stage of cleft lip and palate patients was not found between boys and girls (P = 0.8). Similarly, no significant difference was found in the skeletal age of the 3 studied groups without considering the age and sex of participants (P = 0.5). Regarding the similar skeletal maturational stage of cleft lip and palate patients with normal controls in our study, their maxillofacial orthopedic treatment can be initiated at similar time to normal peers.

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