scholarly journals Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Kohei Doi ◽  
Mayu Morimoto ◽  
Masaki Hirabatake ◽  
Nobuyuki Muroi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Antiangiogenic Agents ◽  
Secondary Endpoints ◽  
Denosumab Treatment

Abstract Purpose Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases. Methods The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ. Results Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37–4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63–10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75–8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06–2.96; p = 0.030) were significant risk factors for MRONJ. Conclusion Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.

scholarly journals Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Moe Mouri ◽  
Hideaki Tomita ◽  
Masaki Hirabatake ◽  
Mai Ikemura ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Tooth Extraction ◽  
Proportional Hazards ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Patients With Cancer ◽  
Proportional Hazards Regression ◽  
Before And After ◽  
Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

scholarly journals Risk Evaluation of Denosumab And Zoledronic Acid For Medication-Related Osteonecrosis of The Jaw In Patients With Bone Metastases: A Propensity Score-Matched Analysis

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Kohei Doi ◽  
Mayu Morimoto ◽  
Masaki Hirabatake ◽  
Nobuyuki Muroi ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Propensity Score ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Patient Characteristics ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Close Monitoring ◽  
Patients With Cancer

Abstract Purpose: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.Methods: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.Results: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016). Conclusion: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1113-1113
Author(s):  
V. Beck ◽  
E. Solomayer ◽  
M. Krimmel ◽  
C. Reinert ◽  
T. Fehm
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Gynecological Malignancies ◽  
Dental Procedures ◽  
The Mean ◽  
Number Of Treatment

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.

scholarly journals Risk Factors for Secondary Glaucoma in Patients with Vogt-Koyanagi-Harada Disease

2021 ◽  
Author(s):  
Carlos Alvarez-Guzman ◽  
Curt Hartleben-Matkin ◽  
Raul E. Ruiz-Lozano ◽  
Alejandro Rodríguez-Garcia ◽  
Manuel E. Quiroga-Garza ◽  
...  
Keyword(s):  
Risk Factors ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Secondary Glaucoma ◽  
Angle Closure ◽  
Mexican Mestizo ◽  
Peripapillary Atrophy ◽  
Clinically Significant ◽  
Recurrent Inflammation

Abstract Background: To identify the prevalence and risk factors for secondary glaucoma among Mexican-mestizo patients with Vogt-Koyanagi-Harada Disease (VKH). A retrospective cohort study was conducted to identify the risk factors for developing secondary glaucoma based on demographic, clinical, and epidemiological variables of VKH Mexican-mestizo patients. Risk estimates were calculated using a Cox proportional hazards regression model. Main text: One hundred eyes of 50 patients, 44 (88%) women and 6 men (12%) with a median age of 35.5 years (IQR 29 – 46), and a median follow-up time of 72 months (IQR 13.7 – 126.7) were included for analysis. The prevalence of glaucoma was 20%, with angle-closure glaucoma accounting for 70% of all cases. Significant clinical risk factors for glaucoma development were a chronic recurrent stage at presentation (RR 2.88 95% CI 1.11 – 12.63, p=0.037), more than two episodes of recurrent anterior uveitis (RR 8.52 95% CI 2.02 – 35.92, p<0.001), angle-closure disease (ACD, RR 7.08 95% CI 2.44 – 20.48, p<0.001), iris bombé (RR 5.0 95% CI 2.10 – 11.90, p<0.001), and peripapillary atrophy (RR 3.56 95% CI 1.43 – 8.85, p<0.001). Exposure to prednisone for more than 24 months (RR 9.33 95% CI 2.21 – 39.28, p<0.001) or topical corticosteroid drops for more than 12 months (RR 3.88 95% CI 1.31 – 11.46, p=0.007) were associated with an increased likelihood for secondary glaucoma development. Conclusions: Glaucoma is a frequent complication in patients with VKH, often attributed to mixed pathogenic mechanisms. Chronic disease at presentation, recurrent inflammation, angle-closure mechanisms, iris bombé, and peripapillary atrophy represent clinically significant risk factors for secondary glaucoma development. Prompt and aggressive steroid-spearing immunosuppressive therapy for reaching adequate control of inflammation may lower the risk of glaucoma in VKH patients.

scholarly journals A Modern Cohort of Duodenal Obstruction Patients: Predictors of Delayed Transition to Full Enteral Nutrition

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Sigrid Bairdain ◽  
David C. Yu ◽  
Chueh Lien ◽  
Faraz Ali Khan ◽  
Bhavana Pathak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Enteral Nutrition ◽  
Median Time ◽  
Nutritional Support ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Potential Risk Factors ◽  
Cox Analysis ◽  
Delayed Transition

Background. A common site for neonatal intestinal obstruction is the duodenum. Delayed establishment of enteral nutritional autonomy continues to challenge surgeons and, since early institution of nutritional support is critical in postoperative newborns, identification of patients likely to require alternative nutritional support may improve their outcomes. Therefore, we aimed to investigate risk factors leading to delayed establishment of full enteral nutrition in these patients.Methods. 87 patients who were surgically treated for intrinsic duodenal obstructions from 1998 to 2012 were reviewed. Variables were tested as potential risk factors. Median time to full enteral nutrition was estimated using the Kaplan-Meier method. Independent risk factors of delayed transition were identified using the multivariate Cox proportional hazards regression model.Results. Median time to transition to full enteral nutrition was 12 days (interquartile range: 9–17 days). Multivariate Cox analysis identified three significant risk factors for delayed enteral nutrition: gestational age (GA) ≤ 35 weeks (P < .001), congenital heart disease (CHD) (P=.02), and malrotation (P = .03).Conclusions. CHD and Prematurity are most commonly associated with delayed transition to full enteral nutrition. Thus, in these patients, supportive nutrition should strongly be considered pending enteral nutritional autonomy.

Graft-Versus-Host Disease (GVHD) in Cord Blood Transplantation (CBT): Risk Factors, Clinical Manifestations and Outcomes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2977-2977
Author(s):  
Daniel Couriel ◽  
Poliana Patah ◽  
Rima Saliba ◽  
Lawrence Cooper ◽  
Laura Worth ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cord Blood ◽  
Proportional Hazards ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Clinical Manifestations ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Hla Typing ◽  
Significant Difference

Abstract Introduction: Umbilical CBT from mismatched donors can restore hematopoiesis both in children and adults with acceptable rates of severe acute (aGVHD) and chronic GVHD (cGVHD). Acute and chronic GVHD, including risk factors, clinical manifestations and its specific impact on outcomes has not been systematically evaluated in this particular patient population. Objective: To analyze the manifestations of GVHD in CBT, with emphasis on risk factors and impact on overall survival. Methods: Prospective evaluation of aGVHD and cGVHD in 138 adult and pediatric patients undergoing single or double CBT for hematological disorders and solid tumors from 3/96 and 6/07. cord blood units were selected on the basis of a maximum of 2 MM (HLA-A, B, DRB1) and the minimum of 1x107TNC/Kg. Risk factors for aGVHD after CBT were assessed using the Cox proportional hazards method. The estimates of aGVHD and cGVHD were performed accounting for competing risks such as death and engraftment using the cumulative incidence (CI) method. Results: A total of 138 adult (n=78) and pediatric (n=60) CBT were performed in the time period. Median age was 21 (1-64), 58 females and 80 males. The majority received a transplant for hematological malignancies (n= 132), mostly MDS/AML and ALL (n= 98, 71%). The remainder had AA (n= 3) and one a solid tumor (n=1). Seventy-seven patients (56%) were in remission of their disease at the time of transplant. Most patients received a myeloablative regimen (n= 125, 91%), and single cord grafts (n= 81, 59%). Of 100 CBT where HLA typing is available, 39%, 45 and 9% have 1, 2 and 3 mismatched loci respectively. Twenty-four patients (17%) did not engraft. At 3 months post transplant, the CI of grade II-IV aGVHD was 36% (adult 38%, pediatric 34%, p= 0.9), and that of grade III-IV was 12% (adult 14%, pediatric 10%, p= 0.9). Skin was the organ most often involved (84%, adult 71%, pediatric 100%, p= 0.017). In adults skin was the only organ involved in 80% of patients with skin GVHD. Lower GI, upper GI and liver involvement were observed in 24, 18, and 21% of patients respectively, without significant difference between adults and children. The total nucleated cell count (TNC) of the graft was the strongest predictor of aGVHD. In children, active disease at the time of transplant was also significantly associated with higher incidence aGVHD. Other factors analyzed, including number and type of mismatched HLA loci were not significant risk factors for aGVHD. CI of cGVHD was 20%, and significantly lower in children compared to adults (8 vs 31%, p= 0.002). Nonrelapse mortality (NRM) at 2 years was 30%, and significantly lower in children (18 vs 41%, p= 0.007). Only 7/43 (16%) deaths were attributed to aGVHD or cGVHD. Conclusions: CBT can be performed in children and adults with acceptable rates of GVHD, even in the presence of multiple HLA mismatched loci. Most cases of acute GVHD involved the skin, often as the only organ. Chronic GVHD and NRM are significantly higher in adults. GVHD accounts for a relatively small proportion of nonrelapse deaths.

Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 2016-2023 ◽  
Author(s):  
Carina Mihai ◽  
Oliver Distler ◽  
Ana Maria Gheorghiu ◽  
Paul I Constantin ◽  
Rucsandra Dobrota ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Disease Duration ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Digital Ulcers ◽  
Cross Sectional ◽  
The Cross

Abstract Objective In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had DUs (current or previous). Older age, DUs ever and dcSSc were statistically significant risk factors for gangrene in the cross-sectional multivariable model. During a median follow-up of 13.1 months, 16/771 (0.9%) patients developed gangrene. All 16 patients who developed gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the dcSSc subset and longer disease duration. Conclusion In unselected SSc patients, gangrene occurs in about 9% of SSc patients. DUs ever and, to a lesser extent, the dcSSc subset are strongly and independently associated with gangrene, while traditional cardiovascular risk factors could not be identified as risk factors.

Spinal Pial (Type IV) Arteriovenous Fistulae

Neurosurgery ◽  
2013 ◽  
Vol 73 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Bradley A. Gross ◽  
Rose Du
Keyword(s):  
Risk Factors ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Treatment Results ◽  
Arteriovenous Fistulae ◽  
Obliteration Rate ◽  
Type Iv ◽  
Large Patient ◽  
Hemorrhage Risk

Abstract BACKGROUND: Demographics, hemorrhage risk, and results of surgical and endovascular treatment of spinal pial (type IV) arteriovenous fistulae (AVFs) across a large patient group have not been previously reported. OBJECTIVE: To report demographics, hemorrhage rates, and treatment results for these AVFs. METHODS: We performed a pooled analysis via the PubMed and Embase databases through November 2012. Individualized patient data were extracted and analyzed using Cox proportional hazards regression to obtain hazard ratios for hemorrhage risk factors and pooled for baseline demographics and treatment results. RESULTS: We extracted information on 213 patients from 28 studies. Only 1% of lesions were incidental; 93% of patients presented with neurologic deficits and 36% with hemorrhage. Patients with type IVa lesions were significantly older (mean age, 46.9 years) and demonstrated a male sex predilection (68% male). Patients with type IVc lesions were significantly younger (mean age, 18.7 years), had no sex predilection, and had the highest prevalence of syndromic conditions (29% of cases). The annual hemorrhage rate was 2.5% (95% confidence interval [CI]: 1.4%-4.7%), increasing to 5.6% for hemorrhagic fistulae (95% CI: 3.0%-10.7%; hazard ratio: 6.31; 95% CI: 0.69-57.4; P = .10). Patient sex, fistula location, and fistula subclass were not significant risk factors for hemorrhage. The surgical obliteration rate was 88%; 68% of patients improved, 26% were the same, and 6% were worse. The endovascular obliteration rate was 74%; 75% of patients improved, 14% were the same, and 11% were worse. CONCLUSION: We demonstrate the utility of the Anson-Spetzler a-c subclassification and underscore the efficacy of surgical and endovascular spinal AVF treatment.

scholarly journals Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ran Noh ◽  
Doo Hyuck Lee ◽  
Byoung Woon Kwon ◽  
Yong Hyun Kim ◽  
Suk Bae Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Viral Load ◽  
Hepatitis C ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Clinical Impact ◽  
Hcv Rna ◽  
Related Mortality

Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients.Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers.Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63,P=0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71,P=0.014), accompanying cirrhosis (HR = 19.34,P=0.004), and low platelet count (HR = 13.97,P=0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13,P=0.012) and low albumin level (HR = 9.17,P=0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality.Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality.

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