• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.539-546
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• 1999

Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that $IL-l{\beta},\;IL-3,\;TNF-{\alpha},$ bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget's disease.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권4호
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• pp.395-398
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• 2008

Bisphosphonate are a class of drugs with a chemical structure which inhibit bone resorption, actually used for metastatic bone disease, osteoporosis, Paget's disease and multiple myeloma. Significant complication associated with their use is reported recently : mandibular and maxillary osteomyelitis or osteonecrosis. So we here report our case about the patient who was diagnosed of prostate cancer in 2004 April and treated with bisphosphonate(Zoledronic acid-$Zometa^{(R)}$, Novartis Co.) intravenously every 3 to 4weeks at a dose of 4mg to prevent bone metastasis, and also, the patient who came to the hospital due to the bony exposure of mandible and pain in 2006 November and was diagnosed osteomyelitis of mandible as a result of biopsy, bone scan, PET CT examination.

• Clinical and Experimental Reproductive Medicine
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• 제19권2호
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• pp.181-187
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• 1992

Calcitonin exerts a positive effects on bone pain. The relief of bone pain has been well known in Paget's disease and malignancy patients with bone metastasis who were treated with salmon calcitonin. We carried out a clinical study evaluating efficacy of salmon calcitonin in reducing bone pain and improving mobility of the postmenopausal osteoporosis women. Fifty women suffering pain from postmenopausal osteoporosis diagnosed by evidence of radiology and/or dual photon absorptiometry were treated with salmon calcitonin 50 MRC three times per week for 4 weeks. The severity of pain estimated by visual analogue scale(VAS) was reduced significantly in treated patients from $8.6{\pm}0.7$ on day 0 to $2.7{\pm}1.7$ on day 28. The mobility of the patients was improved in 2 weeks after salmon calcitonin treatment. Mild adverse effects were seen in 8(16%) patients; headache in 4(8%), sweating and dizziness in 2(4%), pain at the injection site in 1(2%), nausea and vomiting in 1(2%) patient. The treatment was stopped in 3 patients by their request. Salmon calcitonin was effective in 39(83%) of 47 patients above moderate degree. In conclusion, salmon calcitonin is useful in the treatment of patients with pain from postmenopausal osteoporosis.

• Archives of Plastic Surgery
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• 제41권4호
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• pp.379-386
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• 2014

Background Vulvar defects result chiefly from oncologic resection of vulvar tumors. Reconstruction of vulvar defects restores form and function for the purpose of coitus, micturition, and defecation. Many surgical options exist for vulvar reconstruction. The purpose of this article is to present our experience with vulvar reconstruction. Methods From 2007 to 2013, 43 women presented to us with vulvar defects for reconstruction. Their mean age at the time of reconstruction was 61.1 years. The most common cause of vulvar defect was from resection of vulvar carcinoma and extramammary Paget's disease of the vulva. Method s of reconstruction ranged from primary closure to skin grafting to the use of pedicled flaps. Results The main complications were that of long term hypertrophic and/or unaesthetic scarring of the donor site in 4 patients. Twenty-two patients (51%) were able to resume sexual intercourse. There were no complications of flap loss, wound dehiscence, and urethral stenosis. Conclusions We present a subunit algorithmic approach to vulvar reconstruction based on defect location within the vulva, dimension of the defect, and patient age and comorbidity. The gracilis and gluteal fold flaps are particularly versatile and aesthetically suited for reconstruction of a variety of vulvar defects. From an aesthetic viewpoint the gluteal fold flap was superior because of the well-concealed donor scar. We advocate the routine use of these 2 flaps for vulvar reconstruction.

• 대한골관절종양학회지
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• 제11권1호
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• pp.46-53
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• 2005

목적: Bisphosphonate(BPs)는 endogenous pyrophosphates의 유사체로 Paget's disease, 골다공증, 종양 유발성 골용해와 같은 골격계 질환의 치료에 쓰이고 있으며, 유방암의 골파괴성 전이에 대한 치료제로 사용되어 지고 있다. 골전이의 양상이 골흡수성 및 골생성이 혼합되어 나타나는 전립선암의 전이에서도 치료제의 하나로 이용되고 있다. BPs는 파골세포성 골흡수가 과하게 일어난 질환에 대해서는 비교적 널리 알려져 있지만, 골종양 세포에 대한 직접적인 효과에 대해서는 아직 밝혀져 있지 않다. 가장 강력한 질소 함유(nitrogen-containing) BPs인 Zoledronic acid(ZOL)로서 골육종이 발현된 nude mouse model을 이용하여 ZOL의 종양 억제능을 생체내 실험으로 확인하고자 하였다. 대상 및 방법: 인간 골육종 세포주로는 MG-63과 HOS 골육종 세포주를 이용하였고, 종양의 크기 변화를 육안으로 확인하기 위하여 GFP 유전자가 형질 전환된 MG-63-GFP, HOSGFP 세포를 6주령된 수컷 마우스 10마리에 각각 피하주사하여 종양의 조각이 $3{\times}3{\times}3$ mm이 될 때까지 사육한 후, ZOL을 120 ug/kg의 농도로 일주일에 2번 피하에 주사하였다. 종양의 크기를 일주일에 두 번씩 측정하고, 형광조명을 이용하여 촬영하였다. 결과: HOS 골육종 세포주를 이용한 생체실험에서 대조군의 종양의 평균 크기는 2,520 $mm^3$이며 ZOL 투여군은 131 $mm^3$로서 94%의 감소를 보이며, MG-63 골육종 세포주를 이용한 생체실험에서는 대조군의 종양의 평균 크기는 2,866 $mm^3$이며 실험군은 209 $mm^3$로서 72%의 감소를 보였다(P<0.05). 결론: Nude mouse를 이용한 생체실험에서 ZOL은 골육종의 세포사멸에 직접적인 영향을 미치며 이것은 앞으로 골육종 치료의 약제중 하나로 선택되어 질수 있다고 판단되며, 종양세포주에 따라 ZOL의 영향이 다를 수 있으므로 ZOL에 감수성 있는 종양세포를 찾아 적용하는 것이 좋을 것으로 사료된다.

• Toxicological Research
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• 제20권3호
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권1호
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• pp.54-61
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• 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 the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.106-111
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• 2009

Bisphosphonates have been approved for Paget's disease, cancer-related hypercalcemia, bone involvement in multiple myeloma or solid tumors and osteoporosis. Although, underlying pathophysiological mechanisms remain unclear, it seems that bisphosphonates inhibit osteoclast precursor cells, modulate migratory and adhesive characteristics and induce apoptosis of osteoclasts. Furthermore impacts on angiogenesis, microenvironment and signal transduction between osteoclasts and osteoblasts. In this report, we present a case of oral bisphosphonates induced osteonecrosis of the mandible in a 84-year-old patient who received for two years. Two tapered screw vent implants(Zimmer, USA) were placed in the area of first and second molar. Two weeks later after crowns restored, some inflammatory signs and symptoms were observed on the second molar area. Sequestrum was formed and the sequestrum was removed with the implant. Frequent follow-up checks and oral hygiene maintenances were done and the first molar implant was restored. There is insufficient evidence suggests that duration of oral bisphosphonate therapy correlates with the development and severity of osteonecrosis. Therefore, dentists should not overlook the possibility of development of bisphosphonate induced osteonecrosis in patients who have taken oral forms of medication for less than three years.

• Journal of Periodontal and Implant Science
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• 제39권1호
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• pp.1-8
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• 2009

Purpose: Bisphosphonates are drugs used to suppress osteoclastic activity and to treat osteoporosis, Paget's disease of bone and bone metastasis. The purpose of this report is to review the literatures on bisphosphonates use that could affect bone healing and cause osteonecrosis of the jaws. Materials and methods: Medline research was carried out to find relevant articles on bisphosphonates and osteonecrosis of the jaw. Results: Oral administration of bisphosphonates is reported to decrease the risk of adverse bone outcomes. On the contrary, IV bisphosphonates is known to significantly increase the risk. Prevention of the osteonecrosis of the jaw is primary concern before usage. If the adverse bone reaction takes place, proper management and treatments are required to alleviate pain of patients and prevent further progression of necrosis. Conclusion: Case reports of bisphosphonates induced osteonecrosis of the jaw are increasing. Dentists and physicians should be aware of the higher frequency of osteonecrosis of the jaw in patients receiving IV bisphosphonates and be prepared to prevent and cope with adverse bone reaction.

• Journal of Veterinary Science
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• 제23권4호
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• pp.47.1-47.11
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• 2022

Background: In lipopolysaccharide-induced RAW264.7 cells, Aster tataricus (AT) inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells and MAPKs pathways and critical pathways of osteoclast development and bone resorption. Objectives: This study examined how aster saponin A2 (AS-A2) isolated from AT affects the processes and function of osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264.7 cells and bone marrow macrophages (BMMs). Methods: The cell viability, tartrate-resistant acid phosphatase staining, pit formation assay, polymerase chain reaction, and western blot were carried out to determine the effects of AS-A2 on osteoclastogenesis. Results: In RAW264.7 and BMMs, AS-A2 decreased RANKL-initiated osteoclast differentiation in a concentration-dependent manner. In AS-A2-treated cells, the phosphorylation of ERK1/2, JNK, and p38 protein expression were reduced considerably compared to the control cells. In RAW264.7 cells, AS-A2 suppressed the RANKL-induced activation of osteoclast-related genes. During osteoclast differentiation, AS-A2 suppressed the transcriptional and translational expression of NFATc1 and c-Fos. AS-A2 inhibited osteoclast development, reducing the size of the bone resorption pit area. Conclusion: AS-A2 isolated from AT appears to be a viable therapeutic therapy for osteolytic illnesses, such as osteoporosis, Paget's disease, and osteogenesis imperfecta.