• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.1
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• pp.10-18
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• 2011

Purpose: The purpose of this study is to find out the effects of bisphosphonates (BPs) on the proliferation and the alkaline phosphatase (ALP) activity of human bone marrow derived mesenchymal stem cells (hMSCs), and thus state its correlation with bisphosphonate related osteonecrosis of the jaw (BRONJ). Methods: hMSCs was obtained by collecting and culturing cancellous bone fragments from a patient undergoing iliac bone graft. Alendronate (Aln) and Pamidronate (Pam), Ibandronate (Ibn) were added to the culture media in the concentration from $10^{-3}$ M to $10^{-11}$ M and cell toxicity, viability were measured. For ALP activity evaluation, Aln and Pam were added to the culture media in the concentration from $5{\times}10^{-7}$ M to $1{\times}10^{-8}$ M and were cultured for 1 week, 2 weeks and 3 weeks. ALP activity data were standardized using protein assay. Control groups were prepared for each examination. Results: Aln, Pam and Ibn all failed to increase the proliferation of hMSCs. With 1 week, 2 weeks of $5{\times}10^{-8}$M of Aln treatment, the ALP activity increased. Pam treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and$1{\times}10^{-8}$M. Also Ibn treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and $1{\times}10^{-8}$ M. Conclusion: It is considered that BPs are not capable of improving the proliferation of hMSCs. Also, after a transient increase in the ALP activity with the lower concentration of BPs, the activity decreased again. Therefore, in patients on long-term medication of BPs, the proliferation and osteoblast differentiation of hMSCs are restrained, and thus delayed wound healing and increase in BRONJ complications may occur.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.5
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• pp.225-231
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• 2018

Objectives: The purpose of this study was to investigate the demographic and clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and to elucidate factors affecting recurrence in surgical treatment. Materials and Methods: A total of 51 patients who were diagnosed with MRONJ were analyzed according to demographic and clinical features and treatment results through a retrospective chart review from 2013 to 2017 in the Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul in Korea. Results: Alendronate composed the majority of medication doses (55.6%), followed by ibandronate (20.0%), risedronate (15.6%), and zoledronate (6.7%). Forty patients (88.9%) were given oral medication, and five patients (11.1%) were intravenously treated, and the mean duration of medication use was $61.1{\pm}42.9$ months. A total of 10 patients (22.2%) had a drug holiday before MRONJ-induced dental treatment lasting an average of $6.8{\pm}7.0$ months. MRONJ occurred 2.7 times more in the mandible, with 41 cases (73.2%) occurring in the mandible and 15 cases (26.8%) occurring in the maxilla, and the prevalence of affected posterior parts (premolar-molar) was six times greater than that of the anterior parts (incisor-canine) (48 cases vs 8 cases, 85.7% vs 14.3%). The most common dental cause of MRONJ was tooth extraction (69.6%). Regarding recurrence, there was no statistical difference in recurrence rate according to either site or stage. However, recurrence occurred in 4 out of 34 cases (11.8%) in the primary closure group and 9 out of 20 cases (45.0%) in the secondary healing group, and there was a statistical difference with respect to closure technique. Conclusion: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.1-8
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• 2011

Introduction: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. Materials and Methods: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ${\geq}$ 150 pg/mL, moderate, 100 to 150 pg/mL, high, ${\leq}$100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. Results: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). Conclusion: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.19-30
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• 2008

Osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. The diagnostic methods for osteoporosis include simple radiography, bone scan, DXA (Dual energy X-ray Absortiometry) and biochemical markers of bone turnover. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who already have had fractures and some evidence that estrogen does as well. Bisphosphonate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women and in osteoporotic men as well. Risedronate is more potent and has fewer side effects than alendronate and reduces the incidence of fractures in osteoporotic women. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. All of the agents discussed above prevent bone resorption, whereas teriparatide and strontium increase bone formation and are effective in the treatment of osteoporotic women and men. New avenues for targeting osteoporosis will emerge as our knowledge of the regulatory mechanisms of bone remodeling increases, although issues of tissue specificity may remain to be addressed.

• Korean Journal of Clinical Pharmacy
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• v.31 no.3
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• pp.180-187
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• 2021

Objective: We investigated arthralgia and myalgia associated with the use of oral bisphosphonate (BP) by conducting a survey of patient. Methods: The pharmacists conducted a survey between 1 Oct 2019 and 30 Sep 2020 among patients who were dispensed BP in community pharmacies to assess their demographic and medical characteristics, and their experiences with, and process for pain. Logistic regression analyses were performed to find the risk factors associated with the pain, and the odds ratios (OR) and 95% confidence intervals (CI) were determined. Results: A total of 160 patients who used BP participated in the survey (74 [46.3%] used risedronate; 61 [38.1%] used alendronate; 23 [14.4%] used ibandronate), and 20 (12.5%) of them experienced pain. Significant statistical differences of the characteristics between patients who experienced pain or not were observed regarding menopause, and parity. Compared with women who had one or two parity, women who had more than three parity were associated with the decreased risk of pain (OR, 0.24; 95% CI, 0.04-0.98). Moreover, steady exercise was associated with the decreased risk of pain compared to less exercise (OR, 0.37; 95% CI, 0.14-0.98). Conclusion: Our findings suggest that the risk of pain in BP-treated patients might be different regarding the different ingredients of BP, and dosing frequency. This survey highlights a need for a further safety research to understand the factors influencing the pain associated with the BP treatment.