The patients were classified into three groups based on the type of bisphosphonate used for treatment: the alendronate group, risedronate group, and minodronate group. The F-scale scores were compared among the three groups. The frequency of upper gastrointestinal mucosal injury was also compared among the groups. In this study, upper gastrointestinal mucosal injury was defined as Grade A or more severe esophagitis according to the LA classification or the presence of gastroduodenal ulcers.
Furthermore, the patients were classified into two groups based on the treatment schedule: the weekly group treated with alendronate or risedronate once per week and the monthly group treated with minodronate every four weeks.
The F-scale scores and the frequency of upper gastrointestinal mucosal injury in the two groups were compared. The F-scale scores and frequency of upper gastrointestinal mucosal damage were compared among these groups.
Finally, the patients were classified into two groups based on use or non-use of acid-suppressing agents: the acid-suppressing agent group and the acid-suppressing agent non-use group. The F-scale scores and the incidence of upper gastrointestinal mucosal damage were compared between these two groups. The results are shown as the median value or percentage. The percentage of patients with symptoms was compared among groups using the chi-squared test.
All analyses were performed using the JMP pro 13 software program. Statistical comparisons were performed using the Wilcoxon test or chi-squared test. Statistical comparisons were performed using the Kruskal Wallis test or chi-squared test. Statistical comparisons were performed using the Kruskal-Wallis test or chi-squared test. This study conformed to the ethical guidelines of the Declaration of Helsinki revision and was approved by the ethics committee of Tokyo Women's Medical University.
We obtained informed consent for the study directly when we could contact the patients. In addition, we published the study plan on our hospital's home page. If a patient or a bereaved family member disapproved of the patient's data being used in this study, we deleted the relevant data.
The authors declare no conflicts of interest in association with the present study. All patients were women.
The mean age was 71 years. Alendronate and risedronate were administered once per week in patients, while minodronate was administered every four weeks in 31 patients. Forty-four patients underwent testing for Helicobacter pylori infection; the results were positive in 13 patients Table 7. In all patients, the median F-scale total score was 4 points.
On the other hand, the median F-scale reflux score was 2 points and the median dyspepsia score was 2 points. Endoscopic findings: Endoscopy showed reflux esophagitis without mucosal injury in Esophageal submucosal hematoma 1 patient, 0. Furthermore, 9 4. On the other hand, Interestingly, 69 patients Reflux esophagitis: The median F-scale total score was 4 , 8. In addition, the median F-scale reflux scores were 2 , 5 , and 4.
Gastroduodenal ulcers: The median F-scale total score was 4 points in the 9 patients with ulcers ulcer group and 4 points in the patients without ulcers non-ulcer group. There were no significant differences between the two groups with regard to the F-scale total score, reflux score, or dyspepsia score. In addition, the median F-scale reflux scores were 2 , 2 , and 1 points, respectively, while the median dyspepsia scores were 2 , 2 , and 0 points, respectively Table 5.
The rates of upper gastrointestinal mucosal injury in the alendronate, risedronate, and minodronate groups were In addition, the median F-scale reflux scores were 2 and 1 points, respectively, while the median dyspepsia scores were 2 and 0 points, respectively Table 2.
The rate of upper gastrointestinal mucosal injury in the weekly One hundred forty-one patients used neither antithrombotic agents nor concomitant drugs drug non-use group. In addition, the median F-scale reflux scores were 0 , 3 , 4 , and 2 points, respectively, while the median dyspepsia scores were 1 , 2 , 6 , and 1 points, respectively Table 6.
Upper gastrointestinal mucosal injury was detected in Acid-suppressing agents: The median F-scale total score was 4 points in patients who used acid-suppressing agents acid-suppressing agent group and 4 points in 72 patients who did not use these agents acid-suppressing agent non-use group Table 3.
The total score, reflux score, and dyspepsia score of the two groups did not differ to a statistically significant extent. The incidence of osteoporosis is high among elderly women. In addition, it has been reported that the F-scale score differs between men and women, and that the F-scale questionnaire more frequently detects symptoms in women than in men 11 , 12 ; thus, only women were enrolled in this study.
The reasons for visiting hospital varied among the patients, with some being asymptomatic and others presenting for the assessment of symptoms. Thus, there may have been some bias in the study population. In the patients investigated in this study, the median F-scale total score was 4 points and 70 Upper gastrointestinal endoscopy identified Grade A or more severe reflux esophagitis in 22 Matsuki et al.
They reported that the total score was 5. Yamamichi et al. Okamoto et al. Takeshita et al. In comparison to these healthy subjects, the F-scale score was slightly higher among our patients using oral bisphosphonates. Based on these findings, it seems that oral bisphosphonate therapy does not necessarily cause symptoms or increase the frequency or severity of upper gastrointestinal mucosal injury. In this study, the endoscopic evaluation of reflux esophagitis and gastroduodenal ulcers was performed.
The F-scale reflux score was significantly higher in patients with Grade A-D reflux esophagitis and the dyspepsia score was significantly higher in the special group. Acid reflux is one of the underlying causes of esophageal mucosal injury.
However, the significantly higher dyspepsia score in the special group suggested that esophageal retention of bisphosphonates due to impaired esophageal motility may cause severe local damage desquamative esophagitis and esophageal submucosal hematoma.
There was no significant difference in the F-scale scores between the groups classified on the basis of gastroduodenal damage, probably because the gastric mucosal injury is not only associated with the direct effects of bisphosphonates but also with other factors e. The examination of the relationship between the type of bisphosphonates and the F-scale scores or the frequency of mucosal injury showed that there were no significant differences in the F-scale scores between the alendronate and the risedronate groups.
However, the F-scale total score and the dyspepsia scores were significantly lower in patients treated with minodronate, which is administered every four weeks instead of weekly. On the other hand, there was no significant difference in the rate of mucosal injury between the two groups. One major reason for these differences may be that minodronate is administered every four weeks instead of weekly. Another study 15 compared the extent of upper gastrointestinal damage between patients taking oral risedronate at a dose of 2.
Hagino et al. It is thought that approximately 5 days are required for the regeneration of the gastrointestinal tract epithelium, suggesting that the gastric mucosal injury caused by bisphosphonates theoretically heals within approximately one week. Thus, the gastrointestinal damage associated with severe symptoms may be less frequent in patients taking oral bisphosphonates once per week or every four weeks In the present study, the F-scale total score and dyspepsia score were both lower and symptoms were milder in patients treated with minodronate administered every four weeks in comparison to patients using alendronate or risedronate administered once per week.
This difference may be related to the longer interval between doses, which provides a better chance for mucosal injury to heal if it has occurred ; thus, the symptoms would become milder. Amagase et al. However, there has been no previous comparison of these three BPs in humans.
In the present study, no significant differences were observed among the three drugs. We also evaluated the relationship between the use of other medications with bisphosphonates on the F-scale score and rate of mucosal injury.
It has been reported that the irritant effect of bisphosphonates is weaker than that of NSAIDs or aspirin 19 , When bisphosphonates bind, this prevents PC or other protective phospholipids from binding and producing the hydrophobic barrier that protects the epithelial lining from gastric acid.
The reduction in PC and hydrophobicity theory has been examined in the animal population with rodents. With the knowledge of potential topical gastrointestinal irritation with bisphosphonate use, patients should be educated on proper administration to prevent esophageal complications. Additionally, patients must remain in an upright position for at least 30 minutes after administration to prevent reflux into the esophagus that can occur when in a supine position. The instruction to take bisphosphonates on an empty stomach does not relate to esophageal irritation, but instead allows for greater medication absorption.
It is reported that the incidence of esophageal irritation associated with bisphosphonates increases with age, is more common in the female patient population, and is associated with patients who have history of gastrointestinal problems or are concomitantly taking medications that are also gastrointestinal irritants medications e. Bisphosphonates GI upset, bisphosphonates ulcer mechanism, bisphosphonates cause ulcers, alendronate ulcer mechanism, risedronate GI irritation, esophageal ulcers bisphosphonates.
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