• 대한골관절종양학회지
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• 제18권2호
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• pp.99-103
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• 2012

악성 종양 환자에게서 졸레드론산과 같은 비스포스포네이트를 예방적으로 투여받은 경우 이와 관련한 비전형적 대퇴골 골절의 발생 위험성은 아직까지 명확하게 밝혀진 바가 없으며, 국내에 지금까지 보고된 예가 매우 드물다. 본 증례는 다발성 골수종 환자에서 고농도 졸레드론산을 지속적으로 투여받았던 환자에서 큰 외상의 병력 없이 우측 대퇴골 전자하 부위의 비전형적 골절이 발생한 경우로 폐쇄적 정복술 및 골수강 내 금속정 내고정술로 치료한 경험을 보고하고자 한다.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.164-172
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• 2014

Purpose: To evaluate the incidence, clinicopathological characteristics, treatment outcomes, prognostic factors, and survival of gastric cancer patients with bone metastases. Materials and Methods: Of 4,617 gastric cancer patients who were treated between 2001 and 2013, 176 patients with bone metastases were analyzed. Results: The incidence of bone metastasis was 3.8%. The most common histopathological subtype was adenocarcinoma (79%) with poor differentiation (60.8%). The median interval from the diagnosis to bone metastasis was 11 months. The median survival time after bone metastasis was 5.4 months. Factors that were associated with longer median survival times included the following: isolated bone metastasis (P=0.004), well-differentiated tumors (P=0.002), palliative chemotherapy (P=0.003), zoledronic acid treatment (P<0.001), no smoking history (P=0.007), and no metastatic gastric cancer at the time of diagnosis (P=0.01). On the other hand, high levels of lactate dehydrogenase (LDH) (hazard ratio [HR]: 1.86; P=0.015), carcinoembryonic antigen (CEA) (HR: 2.04; P=0.002), and carbohydrate antigen (CA) 19-9 (HR: 2.94; P<0.001) were associated with shorter survival times. In multivariate analysis, receiving zoledronic acid (P<0.001) and performance status (P=0.013) were independent prognostic factors. Conclusions: Smoking history, poor performance status, poorly differentiated adenocarcinoma, and high levels of LDH, CEA, and CA 19-9 were shown to be poor prognostic factors, while receiving chemotherapy and zoledronic acid were associated with prolonged survival in gastric cancer patients with bone metastases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5379-5383
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• 2013

Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations ($0{\mu}M$, $0.01{\mu}M$, $0.1{\mu}M$, $1{\mu}M$, 5${\mu}M$, $30{\mu}M$) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at $1{\mu}M$ in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

• Journal of Radiation Protection and Research
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• 제41권3호
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• pp.253-259
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• 2016

Background: This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. Materials and Methods: C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Results and Discussion: Treatment of ZA ($100{\mu}g{\cdot}kg^{-1}{\cdot}week^{-1}$) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. Conclusion: The results indicate that ZA can prevent radiation-induced bone loss in mice.

• Journal of Oral Medicine and Pain
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• 제44권1호
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• pp.31-34
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• 2019

The aim of this case report is to present a case of 68-year-old male with a history of multiple myeloma and the intravenous use of Zometa (zoledronic acid) who had developed medication-related osteonecrosis of the jaw (MRONJ) following a hot pizza burn to the palate. Clinical and radiographic findings revealed grade 1 MRONJ of the right side of the hard palate. Soft tissue trauma and delayed epithelialization may be associated with some cases of MRONJ. Patients on anti-resorptive medications or anti-angiogenic drugs should be informed of the risk of bone exposure and subsequent MRONJ secondary to physical/chemical insults to the bone and soft tissue in the oral cavity.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6539-6540
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• 2012

• 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.

• Journal of Periodontal and Implant Science
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• 제51권4호
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• pp.264-275
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• 2021

Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.607-608
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• 2013