• The korean journal of orthodontics
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• v.29 no.1 s.72
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• pp.95-106
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• 1999

This study was performed to examine the effect of bisphosphonate, an inhibitor of bone resorption, on the formation of osteoclast and bone resorption during experimental tooth movement. Whether bisphosphonate has a cytotoxicity in high dose was also examined. Eighty-seven male Sprague-Dawley rats, weighing 260-350g, were classified into normal (no appliance + $0.9\%$ NaCl), control (appliance + $0.9\%$ NaCl) and four bisphosphonate-treated (appliance + 0.8, 4, 20 or 100mg/kg) groups. The maxillary left first molar was moved mesially with the tipping movement using 50-70g of force. Bisphosphonate(etidronate disodium) was injected intraperitoneally with a dose of 0.8, 4, 20, or 100 mg/kg simultaneously with the application or the orthodontic force. They were killed at day 1, 3, or 7 after the application or the orthodontic force. The activities of serum acid phosphatase and lactate dehydrogenase (LDH) were assayed, and osteoclasts and the degree of bone resorption were examined histologically. The results obtained were as follows: 1. Acid phosphatase activities were significantly higher in the appliance groups, both control and bisphosphonate-treated (4, 20, and 100 mg/kg) groups, at days 1 and 3 than these in normal. At day 1, bisphosphonate-treated(4, 20mg/kg) groups showed even higher acid phosphatase than control. However, at day 7, no significant difference was noted between the control and bisphosphonate-treated groups. 2. LDH activities in the 4, 20mg/kg bisphosphonate-treated groups were increased during the experimental Periods examined, but there were no significant differences in the 0.8, 100mg/kg bisphosphonate-treated groups. 3. There was no bone resolution at day 1, but severe bone resorption was observed at days 3 and 7 in the control. Bone resorption was reduced by bisphosphonate-treatment at day 3. Bone resolution observed at day 7 was similar between the control and bisphosphonate-treated groups. 4. Few osteoclasts were observed at the alveolar bone in the control and bisphosphonate-treated groups at day 1. At day 3, numerous osteoclasts were shown in the control, the degree of which was reduced in bisphosphonate-treated groups. These results suggest that the inhibition of the osteoclast formation was not the mechanism of bone resorption by the bisphosphonate-treatment during experimenal tooth movement. There was no distinct cytotoxicity with a high dose of bisphosphonate. And the drug should be administrated repeatedly to maintain the inhibitory effect of bone resolution.

• The Journal of the Korean dental association
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• v.49 no.7
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• pp.372-377
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• 2011

Bisphosphonates are widely used in the management of osteoporosis patients. Many reports and clinical studies have published a relationship between necrotic bone lesions localized to the jaw and the use of chronic bisphosphonate therapy. This osteonecrosis named bisphosphonate-related osteonecrosis of the jaw(BRONJ). This article described the mechanism, chemical structure, indication, risk factor of the bisphosphonate.

• The korean journal of orthodontics
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• v.26 no.2 s.55
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• pp.163-174
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• 1996

The purpose of this study was to examine the effects of bisphosphonate and indomethacin, blockers of bone resorption with different mechanisms, on alveolar bone remodeling. Male rats were divided into control, bisphosphonate and indomethacin groups, and then each group was divided info an experimental side and a control side according to the force application. Bisphosphonate(6.3mg/kg,$2.52x10^{-2}mol/L$) and indomethacin (9mg/kg, $2.52x10^{-2}mol/L$) were injected 6 hours and 1 hour before or 24 hours after the force application. The rats were killed 72 hours after the force application and histologic examination was perfomed. The values of serum acid phosphatase and lactate dehydrogenase were also measured in the control md experimental groups treated with bisphosphonate or indomethacin 1 hour before the force application. In the experimental side, the least number of osteoclasts was noted in the groups treated 1 hour before the force application with indomethacin or bisphosphonate, while there were no differences between the control and the groups treated with drugs 6 hours before or 24 hours after the force application. In the control side, the number of osteoclasts was not inecreased with no differences among the groups. Histologic examination revealed a severe alveolar bone resorption in the control group and the groups treated with indomethacin 6 hours before or 24 hours after the force application. Indomethacin treatment 1 hour before the force application and bisphosphonate treatment at any time significantly attenuated the bone resorption. Electron microscopically, ruffled border and clear zone of osteoclasts were observed in the control and indomethacin groups, while some osteoclasts were detached from the bone surface and exhibited dull cellular projections in the bisphosphonate groups. The bisphosphonate and indomethacin groups showed lower values of acid phosphatase and lactate dehydrogenase than the control group. The acid phosphatase value in the bisphosphonate group was lower than that in the indomethacin group, whereas there was no difference in the lactate dehydrogenase value between the groups. These results suggest that bisphosphonate reduces the activity of osteoclasts as well as the number of osteoclasts and that indomethacin reduces the number of osteoclasts without affecting the activity of osteoclasts. Bisphosphonate has a larger inhibitory effect on bone resorption md thus less limitation in the application time than indomethacin.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.508-514
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• 2010

Bisphosphonates are used effectively for many medical conditions, such as multiple myeloma, Paget's disease, osteoporosis, etc. However, recently, osteonecrosis of the jaw was observed in patients receiving long-term bisphosphonate therapy, including oral administration. This osteonecrosis is refractory, and complete recovery is not guaranteed despite a standard treatment protocol being established by many associations related to oral and maxillofacial surgery. The treatment outcome of oral bisphosphonate-related osteonecrosis of jaw (BRONJ) is reported with a review of the relevant literature.

• The Journal of the Korean dental association
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• v.49 no.7
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• pp.389-397
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• 2011

Bisphosphonate inhibits the function of osteoclast, so they are widely used for multiple myeloma, Paget's disease, metastatic malignant bone disease, and severe osteoporosis. This drug is very effective for preventing severe complication of osteoporosis, some unpredictable complication occurred such as esophageal malignancy, atypical fracture of femur, and osteonecrosis of the jaw. Bisphosphonate related osteonecrosis of the jaw (BRONJ) is closely related with invasive, open bone surgery like tooth extraction. BRONJ associated with dental implant is rare, however, as the use of bisphosphonate increase, BRONJ cases with dental implant are increasing. In this article, we will describe the considerations during dental implant treatment for patient under bisphosphonate therapy.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.2
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• pp.57-61
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• 2014

Bisphosphonate is used widely for osteoporosis treatment, but a rising concern is the risk of osteonecrosis after long-term bisphosphonate use. Such cases are increasing, suggesting a need for research to prevent and treat bisphosphonate-related osteonecrosis of jaws. A 63-year-old female took bisphosphonate (Fosamax$^{(R)}$) for four years for treatment of osteoporosis and stopped medication two months ago because of unhealed wound. She was treated with marginal mandibulectomy maintaining the inferior border, and a metal plate was placed to prevent mandible fracture. Four months after the mandibulectomy, mandible reconstruction surgery using iliac bone and allograft was done. Six months after reconstruction, implant placement and treatment with an overdenture was done without complications. This study presents a case with a successful result.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.11.1-11.6
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• 2019

Background: Botulinum toxin injection on the masticatory muscle induces the osteopenic condition on the ipsilateral condyle. Bisphosphonate suppresses bone resorption and is used to treat osteopenic or osteoporotic condition. This study aimed to evaluate the effect of bisphosphonate administration on prevention of condylar resorption and botulinum toxin A-induced disuse osteopenia in rats. Results: The volume of the condyle and bone volume/tissue volume (BV/TV, %) showed a strong tendency towards statistical significance (p = 0.052 and 0.058). Trabecular thickness (Tb.Th, mm) and trabecular number (Tb.N, 1/mm) were significantly smaller in the Botox group than in the other groups (p < 0.05). The volume of the condyle and BV/TV in the bisphosphonate 100 and bisphosphonate 200 groups showed similar values when compared with the control group. Conclusion: Bisphosphonate administration after botulinum toxin A injection in the masticatory muscles appears to prevent condyle resorption and botulinum toxin-induced disuse osteopenia in rats.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.5
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• pp.353-360
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• 2009

Bisphosphonates are compounds widely used in the treatment of various metabolic and malignant bone disease. Recently, an association between bisphosphonate use and a rare dental condition termed 'osteonecrosis of the jaw(ONJ)' has been reported. Bisphosphonate-related osteonecrosis of the jaw(BRONJ) is rare, but serious, side effect of bisphosphonate therapy in affected patients. It is characterized by poor wound healing and spontaneous intra-oral soft tissue break down, which lead to exposure of necrotic maxillary and mandibular bone. We reviewed 11 patients of BRONJ visited Ajou University Hospital Dental clinic from May 2007 to November 2008. The management of the patients included cessation of bisphosphonate therapy and various surgical restorative procedures and conservative care there after. Aggressive debridement is contraindicated. A new complication of bisphosphonate therapy administration, osteonecrosis of jaws, seems to be developing. The improved results after cessation of the medication should make clinicians reconsider the merits of the rampant use of bisphosphonates, while further investigation is needed to completely elucidate this complication.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.48 no.4
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• pp.219-224
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• 2022

Objectives: There have been few studies to date on the residual effect of bisphosphonate. This study investigated the radiographic changes of mandibular cortical thickness upon bisphosphonate drug holiday. Materials and Methods: This retrospective study includes 36 patients diagnosed with MRONJ (medication-related osteonecrosis of the jaw) at Ajou University Dental Hospital in 2010-2021. All patients stopped taking bisphosphonate under consultation with the prescribing physicians. Panoramic radiographs were taken at the start of discontinuation (T₀), 12 months after (T₁), and 18 months after (T₂) discontinuation of bisphosphonate, respectively. Mental index and panoramic mandibular index were calculated using Ledgerton's method. Paired t-tests were used to analyze differences over time. Results: The difference in indices (mental index and panoramic mandibular index) between T₀ and T₁ was not statistically significant (paired t-test, P>0.05). However, the difference in these indices between T₁ and T₂ was statistically significant (paired t-test, P<0.05). Conclusion: The cortical thickness of the mandible decreased in the late stage (after 18 months) as observed by panoramic radiograph.

• The Journal of Advanced Prosthodontics
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• v.5 no.4
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• pp.374-381
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• 2013

PURPOSE. The purpose of this study was to evaluate the effect of alendronates on bone remodeling around titanium implant in the maxilla of rats. MATERIALS AND METHODS. The maxillary first molars were extracted and customized-titanium implants were placed immediately in thirty male Sprague-Dawley rats. The rats were divided into experimental (bisphosphonate) group and control group. At 4 weeks after implantation, the rats in the bisphosphonate group were subcutaneously injected with alendronate three times a week for 6 weeks where as the rats in control group were injected with saline. The rats were sacrificed at 1, 2, 3, 4, or 6 weeks after starting of injection and maxillary bones were collected subsequently. Alveolar bone remodeling around the implants were evaluated by radiographic and histologic analysis. Microarray analysis and immunohistomorphologic analysis were also performed on one rat, sacrificed at 6 weeks after starting of injection, from each group. Statistical analysis was performed using repeated measures analysis of variance and independent t test at a significance level of 5%. RESULTS. There was no statistically significant difference in the bone area (%) around implant between the bisphosphonate group and the control group. However, the amount of empty lacuna was significantly increased in the bisphosphonate group, especially in the rats sacrificed at 4 weeks after starting of injection compared to that of the corresponding control group. The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. CONCLUSION. Alendronate may not decrease the amount of osteoclast. However, the significantly increased amount of empty lacuna in the bisphosphonate group may explain the suppression of bone remodeling in the bisphosphonate group.