• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.23-31
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• 2009

The aim of this study was to evaluate the pharmacokinetic parameters of two risedronate preparations. The clinical assessment was conducted on 46 healthy volunteers who received one tablet (Risedronate sodium 35 mg/tablet) in the fasting state, in a randomized balanced $2{\times}2$ cross-over study design. After dosing of one tablet containing 35 mg risedronate sodium, blood samples were collected serially for a period of 48 hours. Plasma was analyzed for risedronate by using LC/MS/MS assay method. The analysis system was validated in specificity, accuracy, precision, and linearity. $AUC_t$, (the area under the plasma concentration-time curve from the zero-time to 48 hr) was calculated through the trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) were compiled from the plasma risedronate concentration-time data of each volunteer. No significant sequence effect was found for the pharmacokinetic parameters indicating that the cross-over design was properly performed. The 90 % - Confidence intervals of the $AUC_t$ ratio and the $C_{max}$ were from log 0.8752 to log 1.1888 and log 0.8457 to log 1.1478, respectively. These values were within the acceptable intervals between 0.80 and 1.25. Therefore, this study demonstrated that no statistically significant difference was identified with respect to the rate and extent of absorption.

• Journal of Korean Neurosurgical Society
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• v.46 no.1
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• pp.45-51
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• 2009

Objective : To evaluate the potential effects of risedronate (RIS) which shows a higher anti-resorptive effect among bisphosphonates, after a posterolateral lumbar intertransverse process spinal fusion using both autograft and allograft in a rat model. Methods : A totoal of 28 Sprague-Dawley rats were randomized into 2 study groups. A posterolateral lumbar intertransverse process spinal fusion was peformed using both autograft and allograft in a rat model. Group I (control) received 0.1 mL of steril saline (placebo) and Group II (treatment) received risedronate, equivalent to human dose (10 ${\mu}g$/kg/week) for 10-weeks period. Results : The fusion rates as determined by manual palpation were 69% in the group I and 46% in the group II (p = 0.251). According to radiographic score, the spinal segment was considered to be fused radiographically in 7 (53%) of the 13 controls and 9 (69%) of the 13 rats treated with RIS (p = 0.851). The mean histological scores were 5.69 ${\pm}$ 0.13 and 3.84 ${\pm}$ 0.43 for the control and treatment groups, respectively. There was a significant difference between the both groups (p = 0.001). The mean bone density of the fusion masses was 86.9 ${\pm}$ 2.34 in the control group and 106.0 ${\pm}$ 3.54 in the RIS treatment group. There was a statistical difference in mean bone densities of the fusion masses comparing the two groups (p=0.001). Conclusion : In this study, risedronate appears to delay bone fusion in a rat model. This occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuation of risedronate postoperatively during acute fusion period may be warranted.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.79-84
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• 2010

Osteoporosis was traditionally defined by the occurrence of nontraumatic fractures, especially of the spine, in the setting of low bone mass. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. Risedronate sodium is a bisphosphonate class used by oral formulation. In this study, risedronate was transdermally delivered by iontophoresis. Effects of polarity, pH, current density, and drug concentration were studied using a side-by-side diffusion cell including the hairless mice skin. In addition we studied effect of enhancers. The flux was evaluated by HPLC/UV system. The amount of transported drug under iontophoretic delivery was approximately 186 fold higher than that under passive delivery. Flux was proportional to the increase of drug concentration and current density. The flux was observed about 0.68mg/$cm^2$ when the amout of Propyleneglycol monolaurate (PGML) used 1% as enhancer. Results indicated that iontophoresis is an effective method for transdermal administration of risedronate sodium

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.37-38
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• 2011

• Bulletin of the Korean Chemical Society
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• v.31 no.9
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• pp.2561-2564
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• 2010

The accurate determination of bisphosphonate levels in bone and biological fluids is important in both clinical and pharmacological/toxicological studies; however, the quantitative analysis of the bisphosphonate is difficult because its concentration is quite low in most of biological sample. A novel fluorescent chemosensor (FCS)-based measurement method of bisphosphaonate levels using Naphta-diDPA-$2Zn^{2+}$ (NadDPA-$2Zn^{2+}$, DPA = dipycolylamine), an excellent FCS previously used for detecting PPi, was developed. By the FCS method, the concentration of bisphosphonates having no fluorophores can be determined analyzed with sufficient sensitivity. The results of this study indicate that the FCS-based measurement can be a useful method to analyze bisphosphonates in biological samples.

• Korean Journal of Clinical Pharmacy
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• v.24 no.2
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• pp.98-105
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• 2014

Purpose: The aim of this study was to compare retrospectively the efficacy of anti-osteoporotic agents (RAL-Raloxifene 60 mg, ALD-weekly alendronate 70 mg, RSD-weekly risedronate 35 mg, AVD3-weekly alendronate 70 mg/vitamin $D_3$ 2800IU, IBD-quarterly IV ibandronate 3 mg/3 ml, ZLD-yearly IV zoledronate 5 mg/100 ml) in postmenopausal patients with osteoporosis or osteopenia. Method: This study retrospectively reviewed medical record and compared the lumbar spine BMD percentage changes of each medicine group one year later from the baseline. 209 patients (27, 50, 60, 30, 35, and 7 patients in RAL, ALD, RSD, AVD3, IBD, and ZLD groups, respectively) are within the inclusion criteria for the study. Results: From baseline to month 12, lumbar spine BMD increased significantly larger with bisphosphonate groups, compared to SERM (p < 0.05). In all bisphosphonate groups, the lumbar spine BMD were increased significantly from baseline. Of the bisphosphonates, the changes from baseline in BMD of IV bisphosphonates were more larger than those of oral bisphosphonates, and yearly, quarterly bisphosphonates yielded significantly greater BMD gains, compared with weekly bisphosphonate groups (p<0.05). In addition, patients receiving 70 mg weekly alendronate+vitamin D3 had greater gains in BMD than alendronate Single preparation (p<0.05). Conclusion: Bisphosphonates yielded significantly greater BMD gains than SERM. Of the bisphosphonates, the changes from baseline in BMD of yearly, quarterly IV bisphosphonates yielded significantly greater BMD gains, compared with weekly oral bisphosphonate groups. In addition, vitamin D3 plays an significant role in BMD gains.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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• pp.1-19
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• 2019

Objectives: To select the optimal ranges showing obvious synergic anti-osteoporotic potential after adjust mixed formula consisted of Morindae Radix (MR) and Cistanchis Herba (CH) as compared with those of each single formula or risedronate sodium (RES) using bilateral ovariectomized (OVX) female mice. Methods: Fourteen groups, total eight sham or 104 OVX mice were selected based on the body weights at 34 days after OVX surgery. After that, 9 types mixed compositions, single formula of MR and CH, and RES were orally administered for 35 days. And we measured changes in body weight and gain, femur weight, bone mineral density (BMD), bone strength (failure load) and mineral content - calcium (Ca) and inorganic phosphorus (IP), osteocalcin contents and bone specific alkaline phosphatase (bALP) activities of all mice. Results: The OVX-induced estrogen-deficient osteoporotic signs were significantly inhibited by 35 days of continuous oral treatment of all treated mice as compared with OVX control mice. Especially, MR:CH 1:3 and 1:1 mixed formula treated mice showed significantly more favorable inhibitory activities against estrogen-deficient osteoporosis symptoms as compared to those of each single formula of MR and CH. Although RES also ameliorated the decreases of the femur BMD, strength and trabecular bone architectures through the inhibited the increases of bone turnover, but they did not critically influenced on the bone formations. Conclusions: The results suggest that MR:CH 1:3 mixed formula showed somewhat lower anti-resorptive effects as compared to those of RES, but they also showed bone formation effects. therefore, it is expected that MR:CH 1:3 mixture will be promising as a potent protective agents for relieving the osteoporosis in menopausal women.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.4
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• pp.16-38
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• 2018

Objectives: The objective of this in vivo study is to observe the anti-osteoporotic activities of Gojineumja aqueous extracts (GJEJ) on the ovariectomized (OVX) mice as compared to those of risedronate sodium (RES). Methods: Thirty five days after bilateral OVX, GJEJ was orally administered, for 35 days once a day and then the changes on the body weight and gain during experimental periods, femur weights, bone mineral density (BMD), bone strength (failure load), mineral contents - calcium (Ca) and inorganic phosphorus (IP), histological profiles and histomorphometrical analyses at sacrifice were conducted with serum biochemistry - osteocalcin contents and bone specific alkaline phosphatase (BALP) activities. And the results of GJEJ were compared with RES orally administered OVX mice. Results: As a result of OVX, noticeable increase of body weight and gains and serum osteocalcin levels, decrease of serum BALP activities, femur weights, femur Ca and IP contents, BMD and strength were observed as compared to those of sham control mice, respectively. Also, the decrease of all histomorphometrical indices indicating the bone mass and structure, and the increase of indices about resorption were also detected in the femur of OVX control. However, these estrogen-deficient osteoporotic signs were significantly and dose-dependently inhibited by 35 days of continuous oral treatment of GJEJ, at dose levels of 500, 250 and 125 mg/kg, respectively. Especially, GJEJ 500 mg/kg showed favorable inhibitory activities against estrogen-deficient osteoporosis symptoms induced by OVX as comparable to those of RES 2.5 mg/kg. Conclusions: The results in this study suggest that oral administrations of GJEJ have clear dose-dependent favorable anti-osteoporotic activities in OVX mice.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.494-502
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• 2018

Objective : The loosening of pedicle screws (PS) is one of the frequent problems of spinal surgery in the patients with osteoporosis. Previous studies had revealed that intermittent injection of teriparatide could reduce PS loosening by improving bone mass and quality when their patients took parathyroid hormone for a considerable duration before surgery. However, although the teriparatide is usually used after spine surgery in most clinical situations, there was no report on the efficacy of teriparatide treatment started after spine surgery. The purpose of this retrospective study was to examine the efficacy of teriparatide treatment started immediately after lumbar spinal surgery to prevent pedicle screw loosening in patients with osteoporosis. Methods : We included 84 patients with osteoporosis and degenerative lumbar disease who underwent transforaminal interbody fusion and PS fixation and received parathyroid hormone or bisphosphonate (BP) postoperatively. They were divided into teriparatide group (daily injection of $20{\mu}g$ of teriparatide for 6 months, 33 patients, 172 screws) and BP group (weekly oral administration of 35 mg of risedronate, 51 patients, 262 screws). Both groups received calcium (500 mg/day) and cholecalciferol (1000 IU/day) together. The screw loosening was evaluated with simple radiographic exams at 6 and 12 months after the surgery. We counted the number of patients with PS loosening and the number of loosened PS, and compared them between the two groups. Clinical outcomes were evaluated using visual analog scale (VAS) and Oswestry disability index (ODI) preoperatively, and at 12 months after surgery. Results : There was no significant difference in the age, sex, diabetes, smoking, bone mineral density, body mass index, and the number of fusion levels between the two groups. The number of PS loosening within 6 months after surgery did not show a significant difference between the teriparatide group (6.9%, 12/172) and the BP group (6.8%, 18/272). However, during 6-12 months after surgery, it was significantly lower in the teriparatide group (2.3%, 4/172) than the BP group (9.2%, 24/272) (p<0.05). There was no significant difference in the number of patients showing PS loosening between the teriparatide and BP groups. The teriparatide group showed a significantly higher degree of improvement of the bone mineral density (T-score) than that of BP group (p<0.05). There was no significant difference in the pre- and post-operative VAS and ODI between the groups. Conclusion : Our data suggest that the teriparatide treatment starting immediately after lumbar spinal fusion surgery could reduce PS loosening compared to BP.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.39 no.1
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• pp.9-13
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• 2013

Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was $70.0{\pm}10.1$ years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.