• Imaging Science in Dentistry
• /
• v.47 no.1
• /
• pp.45-50
• /
• 2017

Purpose: The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. Materials and Methods: The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Results: Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Conclusion: Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

• Journal of Korean Neurosurgical Society
• /
• v.54 no.6
• /
• pp.461-466
• /
• 2013

Objective : Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats. Methods : Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test. Results : High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015). Conclusion : The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

• Journal of Korean Neurosurgical Society
• /
• v.52 no.1
• /
• pp.1-6
• /
• 2012

Objective : The purpose of this study was to evaluate the different patterns of bone loss between the lumbar spine and the femur after ovariectomy in rats. Methods : Twenty-four female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight weeks after operation, six rats from each of the two groups were euthanized. Serum biochemical markers of bone turnover including osteocalcin and alkaline phosphatase (ALP), which are sensitive biochemical markers of bone formation, and the telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption, were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae and femur were determined by micro-computed tomography. Results : Ovariectomized rats were found to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally, 8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss after ovariectomy was more extensive in the 4th lumbar spine compared to the femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular thinning, but in the femur, it was mainly caused by trabecular elimination. Conclusion : The present study demonstrates different patterns of bone loss between the 4th lumbar spine and the femur in ovariectomized rats. Therefore, when considering animal models of osteoporosis, it is important that bone sites should be taken into account.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.42 no.4
• /
• pp.193-204
• /
• 2016

Objectives: This study examined the statistical relevance of whether the systemic predisposing factors affect the prognosis of surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). All cases had undergone bone biopsies to determine the characteristics of the mechanisms of BRONJ by optical microscopy. Materials and Methods: The data included 54 BRONJ cases who underwent surgery and in whom bone biopsies were performed. The results of surgery were evaluated and the results were classified into 3 categories: normal recovery, delayed recovery, and recurrence after surgery. The medical history, such as diabetes mellitus, medication of steroids, malignancies on other sites was investigated for an evaluation of the systemic predisposing factors in relation to the prognosis. The three factors involved with the medication of bisphosphonate (BP) were the medication route, medication period, and drug holiday of BP before surgery. The serum C-terminal cross-linking telopeptide (CTX) value and presence of microorganism colony in bone biopsy specimens were also checked. Statistical analysis was then carried out to determine the relationship between these factors and the results of surgery. Results: The group of patients suffering from diabetes and on steroids tended to show poorer results after surgery. Parenteral medication of BP made the patients have a poorer prognosis after surgery than oral medication. In contrast, the medication period and drug holiday of BP before surgery did not have significance with the results of surgery nor did the serum CTX value and presence of microorganism colony. Necrotic bone specimens in this study typically showed disappearing new bone formation around the osteocytic lacunae and destroyed Howship's lacunae. Conclusion: Although many variables exist, this study could in part, predict the prognosis of surgical treatment of BRONJ by taking the patient's medical history.

• Journal of Korean Academy of Nursing
• /
• v.44 no.5
• /
• pp.504-514
• /
• 2014

Purpose: This study was done to assess the bone mineral density (BMD), biochemical bone turnover markers (BTMs), and factors associated with bone health in young Korean women. Methods: Participants were 1,298 women, ages 18-29, recruited in Korea. Measurements were BMD by calcaneus quantitative ultrasound, BTMs for Calcium, Phosphorus, Osteocalcin, and C-telopeptide cross-links (CTX), body composition by physical measurements, nutrients by food frequency questionnaire and psychosocial factors associated with bone health by self-report. Results: The mean BMD (Z-score) was -0.94. 8.7% women had lower BMD ($Z-score{\leq}-2$) and 14.3% women had higher BMD ($Z-score{\geq}0$) than women of same age. BTMs were not significantly different between high-BMD ($Z-score{\geq}0$) and low-BMD (Z-score<0) women. However, Osteocalcin and CTX were higher in women preferring caffeine intake, sedentary lifestyle and alcoholic drinks. Body composition and Calcium intake were significantly higher in high-BMD. Low-BMD women reported significantly higher susceptibility and barriers to exercise in health beliefs, lower bone health self-efficacy and promoting behaviors. Conclusion: Results of this study indicate that bone health of young Korean women is not good. Development of diverse strategies to intervene in factors such as exercise, nutrients, self-efficacy, health beliefs and behaviors, shown to be important, are needed to improve bone health.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.37
• /
• pp.18.1-18.7
• /
• 2015

Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and aggravation of BRONJ. Methods: Twenty seven rats were divided into 3 groups; Saline group (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got weekly intraperitoneal injection for 4 times and extraction of left maxillary and mandibular 1st, 2nd molars were followed. Consecutive injections were performed, and blood sampling for measurements of C-terminal crosslinked telopeptide of type I collagen and tartrate-resistant acid phosphate 5b rats were performed at the time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated clinically, radiologically and histologically. Results: 12/18 (66.6 %) of experimental group were diagnosed as BRONJ. There was no significant difference in incidence between zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll). Conclusions: Concurrent use of bisphosphonates and steroids increase incidence of BRONJ compared to saline group (l). Zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the rat treated with bisphosphonates and steroids can be considered a novel, reliable and reproducible model to understand pathology of BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.37 no.1
• /
• pp.54-61
• /
• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• Journal of Nutrition and Health
• /
• v.41 no.3
• /
• pp.206-215
• /
• 2008

The purpose of this study was to investigate the effect of manganese (Mn) supplementation on bone status and calcium balance in ovariectomized rats according to the calcium intake levels. Total of 50 Sprague Dawley female rats (6 weeks) were divided into 5 groups and bred for 12 weeks: sham operated control group (SACa), OVX Ca deficiency group (OLCa) with Ca deficiency diet (0.1% Ca modified AIN-93N diet), OVX Ca deficiency & Mn supplement group (OLCaMn), OVX adequate Ca group (OACa; 0.5% Ca AIN-93N diet) and OVX adequate Ca & Mn supplement group (OACaMn). BMD (bone mineral density) of the femur was increased by Mn supplementation in OVX adequate Ca group. However, BMDs of spine, femur and tibia were lowered in OLCa compared to the OLCaMn group. Bone strength of tibia in OLCaMn group was significantly lower than OLCa group. Serum ALP (alkaline phosphatase) and CTx (C-telopeptide of collagen cross-links) levels were significantly higher in ovariectomized rats than those in the sham group, but they were not changed by Mn supplementation. Ca retention rate and Ca absorption rate did not differ among the experimental groups. Urinary Ca excretion was increased by Mn supplementation in Ca deficiency rats. In summary, Mn supplementation resulted in positive effects on bone mineral density ovariectomized rats with which intake adequate Ca. However, Mn supplementation on Ca deficiency ovariectomized rats resulted in decrement of BMO and bone strength by increasing Ca excretion. Therefore, it is encouraged to consider calcium intake levels in supplementation of manganese in order to prevent postmenopausal osteoporosis and to keep bone healthy. (KoreanJNutr2008; 41(3): 206~215)

• Korean Journal of Medicinal Crop Science
• /
• v.24 no.5
• /
• pp.370-374
• /
• 2016

Background: Many menopausal women suffer from health problems including metabolic diseases such as dyslipidemia and osteoporosis. Thus they need natural products and functional foods particularly highly nutritional food products, that can help alleviate these diseases. This study was carried out to determine the effect of Drynariae Rhizoma water extract on the lipid and bone metabolism of ovariectomized Sprague-Dawley rats. Methods and Results: The animals were randomly divided into six dietary groups comprising SHAM-operated rats, OVX rats (normal diet), and OVX-DR rats (Drynariae Rhizoma extract). After 8 weeks, plasma, liver, and fat samples were collected to analyze the lipid metabolism, plasma Ca, alkaline phosphatase (ALP), osteocalcin and C-terminal telopeptide (CTx) concentrations, which are biochemical makers of bone metabolism. The left femurs of rats were also collected for histological analyses. OVX counteracted menopause induced body weight gain, as well as increases in triglycerides, total cholesterol, and free fatty acids. The Drynariae Rhizoma group showed low levels of triglycerides, high HDL-cholesterol, and decreased lipogenesis based on activity of the lipid-regulating enzymes (fatty acid synthase and malic enzyme). Decreased serum levels of ALP and osteocalcin were observed in Drynariae Rhizoma group. Conclusions: The results of this study show that Drynariae Rhizoma extract may effectively regulate hyperlipidemia and improve bone density.

• The Korean Journal of Pain
• /
• v.30 no.2
• /
• pp.86-92
• /
• 2017

Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption. Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of resorption performed by activated osteoclasts, are still the drugs of choice to prevent and treat osteoporosis. The merits of denosumab are reversibility targeting the RANKL, lack of adverse gastrointestinal events, improved adherence due to convenient biannual subcutaneous administration, and potential use with impaired renal function. The known adverse reactions are musculoskeletal pain, increased infections with adverse dermatologic reactions, osteonecrosis of the jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3 days, with maximum reduction occurring by 1 month. The mean time to maximum denosumab concentration is 10 days with a mean half-life of 25.4 days. In conclusion, the convenient biannual subcutaneous administration of 60 mg of denosumab can be considered as a first-line treatment for osteoporosis in cases of low compliance with BPs due to gastrointestinal trouble and impaired renal function.