Prevalencia de osteonecrosis de los maxilares asociada a medicamentos en pacientes tratados con bifosfonatos intravenosos: análisis epidemiológico en Centro del Cáncer - Red de Salud UC-CHRISTUS

Resumen Introducción: La osteonecrosis de los maxilares asociada a medicamentos (OMAM) es una patología que involucra la exposición necrótica de hueso maxilar o mandibular, relacionada al uso de fármacos antirresortivos y antiangiogénicos, con una prevalencia de 0,94%-13% en pacientes oncológicos y con osteoporosis que hacen uso de ellos. Objetivo: Determinar la prevalencia de osteonecrosis de los maxilares en pacientes en tratamiento con bifosfonatos intravenosos (BFIV) en el Centro del Cáncer de la Red de Salud UC-Christus, Santiago de Chile. Material y Método: Se analizaron los datos de pacientes que recibieron tratamiento de bifosfonatos intravenoso entre marzo y septiembre de 2016, con seguimiento por los equipos tratantes. Se consideró para la extracción de datos el género, edad, diagnóstico primario, bifosfonato intravenoso utilizado, tiempo de seguimiento, presencia de metástasis óseas y diagnóstico de OMAM. Resultados: Se obtuvo una muestra de 143 pacientes, con una relación hombre:mujer de 1:2; promedio de edad de 63,2 años; 78% de ellos fueron tratados con ácido zoledrónico y un 22% con pamidronato. Del total de pacientes un 1,4% (n = 2) desarrolló OMAM. Ambos casos con diagnóstico de cáncer de mama en tratamiento con ácido zoledrónico, lo que corresponde al 1,8% de los pacientes en tratamiento con este fármaco. Conclusión: Si bien la OMAM es una patología infrecuente, esta se presenta con alta morbilidad y es de manejo complejo. La prevención y tratamiento de focos infecciosos odontogénicos de pacientes antes, durante o después del tratamiento con BFIV es fundamental para prevenir su desarrollo.

Abstract Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a disease involving exposition of necrotic maxillary and mandibular bone and it's related to antiresorptive and antiangiogenic drugs, with a prevalence that variates from 0,94%-13% in oncologic and osteoporosis patients treated with them. Aim: To determine the prevalence of MRONJ in patients that underwent treatment with intravenous bisphosphonates (IVBP) at Centro del Cancer de la Red de Salud UC-CHRISTUS of Santiago, Chile. Material and Method: Data from patients who received intravenous bisphosphonate treatment between March and September 2016 were analyzed, with follow-ups by their treating teams. Data extraction considered gender, age, primary diagnosis, intravenous bisphosphonate used, follow up time, bone metastases and diagnosis of MRONJ. Results: A sample of 143 patients was obtained with a men:women ratio of 1:2; an average age of 63,2 years, 78% of the patients were treated with zoledronic acid and 22% of the patients with pamidronate. From the total number of patients,1.4% (n = 2) developed MRONJ, both cases had breast cancer as primary diagnosis and in treatment with zoledronic acid, which corresponds to 1.8% of patients being treated with this drug. Conclusion: Although MRONJ is an infrequent disease, it presents high morbidity and complex management. Prevention and treatment of odontogenic infectious foci in patients before, during and after treatment with IVBP drugs is fundamental to prevent this pathology.

Effects of Adding Intravenous Pamidronate to Ongoing Menopausal Hormone Therapy in Postmenopausal Korean Women with Low Bone Mineral Density

OBJECTIVES: We evaluated the effects of adding intravenous pamidronate to ongoing menopausal hormone therapy (MHT) on bone mineral density (BMD) in postmenopausal Korean women with low BMD.METHODS: This retrospective cohort study included 74 postmenopausal women who received MHT for at least 1 year and had a BMD T-score of less than −2.0. Maintaining the same MHT regimen, these women were divided into two groups: oral placebo group (n = 44) and a pamidronate group of patients with gastrointestinal discomfort (n = 30) who received 15–30 mg pamidronate intravenously every 3–12 months. BMD was reviewed at 12-month follow-up. Bone resorption markers in both groups, urinary deoxypyridinoline levels in the placebo group, and serum N-telopeptide of type I collagen in the pamidronate group were assessed at 6 and 12 months.RESULTS: At baseline, the body mass index (BMI), duration of previous MHT, and femur neck (FN) BMD differed between the groups. Within-group analysis revealed that BMD of the lumbar spine (LS) and total hip (TH) significantly increased in the placebo group, whereas those of the LS, FN, and TH increased in the pamidronate group. The increase in BMD of LS was significantly greater in the pamidronate group, after adjusting for BMI and duration of previous MHT (mean change: 3.7% vs. 6.2%; P < 0.001). There were no changes in bone resorption markers in either group.CONCLUSIONS: Adding intravenous pamidronate to ongoing MHT for 12 months might increase LS BMD in postmenopausal Korean women with low BMD.

Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report / Tiosulfato de sodio y pamidronato para el tratamiento de calcifilaxis: reporte de caso

Abstract Introduction: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. Clinical Case: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. Treatment and Outcome: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. Conclusion: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

Resumen: Introducción: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. Caso Clínico: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. Tratamiento y resultado: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. Conclusión: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

Combination treatment of bisphosphonate (pamidronate) and Quercus infectoria semi- purified fraction promotes proliferation and differentiation of osteoblast cell via expression of Osterix and Runx2 marker

Objective: To understand the effects of combination treatment of pamidronate with isolated Quercus infectoria semi-purified fraction (QIsm-F) on human foetal osteoblast cell model (hFOB 1.19 cell line) through assessment of Runt related transcription fraction-2 (Runx2) and Osterix (Osx). Methods: The isolation and purification of QIsm-F were conducted by chromatographic technique. In order to assess relative efficacy of QIsm-F to the osteoblast model, the determination of half maximal effective concentration (EC

Combination treatment of bisphosphonate (pamidronate) and Quercus infectoria semi-purified fraction promotes proliferation and differentiation of osteoblast cell via expression of Osterix and Runx2 marker

Objective:To understand the effects of combination treatment of pamidronate with isolated Quercus infectoria semi-purified fraction (QIsm-F) on human foetal osteoblast cel model (hFOB 1.19 cel line) through assessment of Runt related transcription fraction-2 (Runx2) and Osterix (Osx). Methods:The isolation and purification of QIsm-F were conducted by chromatographic technique. In order to assess relative efficacy of QIsm-F to the osteoblast model, the determination of half maximal effective concentration (EC50) was performed by MTT assay. hFOB 1.19 cel s were cultured in DMEM F-12 and supplemented with 10％ fetal bovine serum along with 1％ penicil in-streptomycin incubated in 5％ CO2 at 37 ℃. Expression of Runx2 and Osx was assessed through western blotting and confirmed with immunofluorescence staining. Results: Results of western blot analysis and immunofluorescence staining demonstrated that compared to hFOB 1.19 cells treated with single individual treatment of QIsm-F and control groups, levels of Runx2 and Osx were elevated with higher fluorescence intensity and more rapid proliferation in hFOB 1.19 cells treated with combined treatment of QIsm-F and pamidronate. Conclusions: The finding demonstrates the synergistic effect between osteoporotic drug pamidronate and established QIsm-F. The combination treatment helps increase the efficiency of pamidronate acting on osteoblast cells by stimulating osteoblast proliferation and differentiation via expression of Runx2 and Osx.

Análisis Histomorfométrico de la Asociación de Aceite de Oliva y Bisfosfonatos en la Remodelación Ósea Periimplantaria / Histomorphometric Analysis of the Association of Olive Oil and Bisphosphonates on Peri-Implant Bone Remodeling

RESUMEN: Los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) presenta propiedades anti-inflamatorias y anti-oxidantes. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) por vía subcutánea y de O vía oral sobre la regeneración tisular de cavidades óseas neoformadas.: 54 ratas macho de la línea Wistar, se dividieron en 6 grupos. Grupo control (C), recibieron solución salina vía subcutánea. Grupo (AL) recibió 0,5 mg de AL/Kg de peso corporal de por vía subcutánea. Grupo (PA) recibió de igual manera que el grupo anterior. Grupo (O) fue tratado con aceite de oliva con la dieta, 50 g/ Kg de comida. Grupo (ALO) recibió tratamiento combinado con AL y O. Grupo (PAO) recibió de igual tratamiento. Los sacrificios para la toma de muestras fueron a los 15, 30, 60 y 90 días. Para los estudios histopatológicos los cortes fueron teñidos con HE y observados con microscopía óptica. Los estudios estadísticos se realizaron a través del análisis de la variancia. A los quince días las áreas de los osteocitos del grupo PA se diferencian significativamente sólo respecto al grupo AL. En cuanto a la Densidad trabecular se observa un incremento de tejido óseo en todos los grupos. O mejora cualitativamente la estructura del hueso trabecular y cortical, preservando la mineralización, el tamaño y la estructura de los cristales minerales Esto sugiere que O representa una opción terapéutica prometedora para la prevención y tratamiento de las patologías óseas.

ABSTRACT: Bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) has anti-inflammatory and anti-oxidant properties. To study the effect of combined treatment with alendronate (AL) and pamidronate (PA) subcutaneously or orally, and on tissue regeneration of newly formed bone cavities, we divided 54 male Wistar rats into 6 groups. Control group (C) received saline subcutaneously. Group (AL) received 0.5 mg of AL / kg body weight subcutaneously. Group (PA) received the same as the previous group. (O) was treated with olive oil diet, 50 g / kg of food. Group (ALO) received combined treatment with AL and O. Group (PAO) received the same treatment. The animals were euthanized for sampling at 15, 30, 60 and 90 days. For histopathology sections were stained with HE and observed these with light microscopy. Statistical studies were performed by analysis of variance. Fifteen days osteocytes areas of the PA group were significantly different only for the AL group. As the density increased trabecular bone tissue was observed in all groups. O qualitatively improved the structure of trabecular and cortical bone mineralization while preserving the size and structure of the mineral crystals. This suggests that O represents a promising therapeutic option for prevention and treatment of bone diseases.

Use of pamidronate for osteoporosis treatment in public health care in Brazil / Uso de pamidronato para o tratamento da osteoporose no sistema público de saúde no Brasil

Abstract Purpose: The use of bisphosphonates for osteoporosis is effective in reducing the risk of fractures. However, oral formulations are sometimes not well tolerated or are contraindicated. Due to its availability in Brazilian public health system, pamidronate is frequently prescribed for osteoporosis, despite the lack of studies demonstrating its anti-fracture efficacy and the absence of FDA or EMEA approval for this purpose. The aim of this study was to evaluate the bone mineral density (BMD) response to pamidronate in a group of women with osteoporosis in a tertiary care hospital. Patients and methods: The medical records of women with osteoporosis who received pamidronate for up to two years of treatment were reviewed. Patients were stratified at high or intermediate risk of fracture. Results: A total of 70 women were in treatment with pamidronate. Among them, 74% were at high risk of fracture. A significant gain in spine BMD after 24 months of treatment was observed (p = 0.012). There was no difference between the groups of high and not high risk of fracture. At the femur, no significant increase in BMD was present, though, a strong negative correlation with high PTH levels (r = −0.61; p = 0.003) was seen. In the multivariate analysis BMI at 12 months had impact in the response to the treatment. Conclusion The intravenous pamidronate in a group of postmenopausal women with predominant high risk of fracture promoted an isolated gain in the spine BMD, even though, clinical randomized trials are needed to confirm its anti-fracture efficacy.

Resumo Justificativa: O uso de bisfosfonatos para a osteoporose é eficaz na redução do risco de fraturas. No entanto, as formulações orais às vezes não são bem toleradas ou são contraindicadas. Em razão da sua disponibilidade no sistema público de saúde brasileiro, o pamidronato é frequentemente prescrito para a osteoporose, apesar da falta de estudos que demonstrem a sua eficácia antifratura e da ausência de aprovação da Food and Drug Administration (FDA) ou da European Medicine Agency (Emea) para essa finalidade. O objetivo deste estudo foi avaliar a resposta da densidade mineral óssea (DMO) ao pamidronato em um grupo de mulheres com osteoporose em um hospital terciário. Pacientes e métodos: Revisaram-se os prontuários médicos de mulheres com osteoporose que receberam pamidronato por até dois anos de tratamento. As pacientes foram estratificadas em risco alto ou intermediário de fratura. Resultados: Estavam em tratamento com pamidronato 70 mulheres. Entre elas, 74% tinham alto risco de fratura. Observou-se um ganho significativo na DMO da coluna vertebral após 24 meses de tratamento (p = 0,012). Não houve diferença entre os grupos de risco de fratura alto e não alto. No fêmur, não foi encontrado aumento significativo na massa óssea; contudo, observou-se uma forte correlação negativa com altos níveis de PTH (r = −0,61; p = 0,003). Na análise multivariada, o IMC aos 12 meses tinha impacto na resposta ao tratamento. Conclusão O pamidronato intravenoso em um grupo de mulheres na pós-menopausa predominantemente com alto risco de fratura promoveu um ganho isolado na DMO da coluna vertebral, embora sejam necessários ensaios clínicos randomizados para confirmar sua eficácia antifratura.

Respuesta completa y prolongada al tratameinto con pamidronato en metástasis pulmonares de un tumor de células gigantes óseo / Complete and prolonged response to treatment with pamidronate in lung metastases from a giant cell tumor of the bone

A pesar de ser considerado benigno, el tumor de células gigantes (TCG) de hueso con baja frecuencia puede presentar metástasis (MTS) a distancia, mayormente pulmonares. El curso clínico de las MTS, aunque habitualmente indolente, es muy variable. Se comunicaron tanto muertes por progresión de MTS, como su regresión sin mediar tratamiento alguno. Los marcadores pronósticos moleculares están aún en desarrollo. El manejo terapéutico de las MTS pulmonares es controversial. Las principales modalidades de tratamiento fueron tradicionalmente la cirugía, la quimioterapia y observación. En la última década los bifosfonatos (BF) y el denosumab, fueron empleados con éxito en el tratamiento adyuvante y neoadyuvante, pero la efectividad de estos fármacos, especialmente los BF, en pacientes con MTS está estudiada en menor medida. Presentamos un caso de MTS pulmonares múltiples histológicamente verificadas de TCG con respuesta completa al tratamiento con pamidronato que continúa a los 7 años de seguimiento (AU)

Although it is considered benign, on rare occasions giant cell tumor (GCT) of bone may present systemic dissemination, predominantly to the lung. The clinical course of metastasis (MTS), while usually indolent, is unpredictable. Both, deaths from progressive lung MTS and regressions without any treatment were reported. Molecular prognostic biomarkers are under development yet. The management of GCT is controversial. Surgical removal, chemotherapy and observation were traditionally the treatment modalities of choice. In the last decade biphosphonates and denosumab were successfully used in the adjuvant and neoadjuvant/unresectable setting. Nonetheless, the effectiveness of these drugs in metastatic disease is less studied. We submit a case report of complete response of multiple histopathologically confirmed unresectable lung MTS of TCG to the treatment with pamidronate with total follow-up length of 7 years (AU)

The effect of low-dose intravenous bisphosphonate treatment on osteoporosis in children with quadriplegic cerebral palsy / 소아과

PURPOSE: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. METHODS: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, 10.9±5.76 years), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5–1.0 mg/kg/day, 2 consecutive days) every 3–4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. RESULTS: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was 4.49±2.22 mg/kg/yr, and the mean treatment period was 10.8±3.32 months. The BMD z score of the lumbar spine showed a significant increase from −4.22±1.24 before treatment to −2.61±1.69 during treatment (P=0.008). Alkaline phosphatase decreased during treatmentn (P=0.037). Significant adverse drug reactions and new fractures were not reported. CONCLUSION: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density

PURPOSE: Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients. METHODS: Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated. RESULTS: After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm2 after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells

BACKGROUND: N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. METHODS: Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10⁻¹², 10⁻¹⁰, 10⁻⁸, and 10⁻⁶ M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. RESULTS: Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. CONCLUSIONS: Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression.

Treatment of Polyostotic Fibrous Dysplasia of the Thoracic Spine with Intravenous Pamidronate: Result from 9 Months Follow Up

Fibrous dysplasia of the spine is very rarely observed. We reported a case of a 57-year-old woman, who presented with neck and bilateral shoulder pain with histologically confirmed fibrous dysplasia, involving the first and second thoracic vertebrae. Clinical and radiological findings were not specific for fibrous dysplasia. The histological biopsy was required for a confirmed diagnosis. Endocrine and metabolic evaluations are required to rule out diseases such as hyperthyroidism, Cushing syndrome and osteomalacia. Fibrous dyplasia can be managed by appropriate medical and surgical treatments based on the patient's neurological status and symptoms. Our patient was given intravenous pamidronate 60mg/day for 3 days. After 9 months, her initial symptoms were improved, but computed tomography scan of the thoracic spine showed no change of the lesions.

Evaluation on the efficacy of pamidronate disodium in treatment of osteocarcinoma / 中国生化药物杂志

Objective To investigate the efficacy of disodium pamidronate in treatment of bone metastasis cancer .Methods 50 cases of bone metastasis cancer were divided into control group and experimental group according to different medication, 25 cases in each group.Control group was treated by chemotherapy, experimental group was treated on the basis of control group with disodium pamidronate 45 mg+0.9%sodium chloride solution 500 mL, intravenous drip.Pain maintenance time, patient pain grading and serum NTx levels were compared after treatment.ResuIts Compared with control group,pain maintenance time of experimental group was longer(P <0.05),pain level overall score was lower,NTx was lower(P <0.05). ConcIusion Disodium pamidronate can inhibit bone metastasis cancer patients with the degree of pain, reduce the levels of serum NTx.

Osteogenesis imperfecta type V: A repost of two Filipino families and review of literature

Osteogenesis imperfecta (Ol) type V is distinct Ol phenotype that has recently been described. Patients with this phenotype present characteristically with interosseous membrane calcification and hyperplastic callus formation. We present the clinical and radiographic characteristics of two Filipino families diagnosed to have Ol type V. Through this review of cases, we aim to educate healthcare providers by highlighting salient clinical and radiographic features to aid in the recognition of this specific Ol phenotype, difficulties in diagnosis, current practices in management and fracture prevention, and issues in genetic counseling.

Long-term Follow-up of Metaphyseal Sclerotic Lines in Children Treated with Pamidronate

PURPOSE: Bisphosphonates are widely used for the management steroid-induced osteoporosis (SIO) in children. With the increasing use of bisphosphonates, there have been reports of abnormal radiological findings in the growing skeleton. Therefore, their use in pediatric patients remains controversial. The present study was conducted to evaluate the long-term follow-up radiographic features, particularly metaphyseal sclerotic lines, in children who receive pamidronate therapy for nephropathy. METHODS: Twenty-four children with nephropathy treated with oral calcium and pamidronate (mean duration, 9 months; dose, 100 mg daily), were evaluated retrospectively. All patients had SIO secondary to chronic glucocorticoid therapy for treating nephropathy. Long bone radiographic imaging was performed before treatment with pamidronate, and at follow-up, several years later. Physeal growth rates were estimated by measuring the distance that the sclerotic lines moved on the radiographs during the corresponding time intervals. RESULTS: The mean follow-up period was 138 months. Long bone radiographs showed well-defined sclerotic lines at the metaphyseal ends, progressively moving from the physeal plate to the diaphysis, in all patients. The mean rate of movement of the sclerotic line was 6.21 mm per year. In 12 patients, the lines disappeared. The mean rate of growth in height was 7.33 cm per year. CONCLUSIONS: Results of long-term follow-up suggest that the metaphyseal sclerotic lines associated with pamidronate treatment tend to disappear without affecting overall skeletal growth. Bisphosphonate treatment for SIO in children with nephropathy seems to be safe, although further studies in larger number of patients are needed.

The efficacy of disodium Pamidronate in the treatment of primary hyperparathyroidism complicated by hypercalcemic crisis / 中华急诊医学杂志

Objective To study the efficacy of disodium pamidronate in the treatment of patients with primary hyperparathyroidism (PHPT) complicated by hypercalcemic crisis.Methods A total of 9 patients (12 cases) admitted into our hospital were diagnosed as PHPT complicated by hypercalcemic crisis.Of them,4 patients had parathyroid carcinoma,3 patients had parathyroid adenoma,2 patients had parathyroid hyperplasia.The intravenous disodium pamidronate was given for 12 times in all 9 patients.Serum calcium were monitored before and after treatment.Results Before the treatment,the serum calcium levels was 3.75 (3.66,3.99) mmol/L.On the second and third day after the treatment with disodium pamidronate,the serum calcium levels were 3.44 (2.95,3.78) mmol/L and 2.79 (2.50,3.14) mmol/L.The lowest level of serum calcium after treatment was 2.25 (2.00,2.55) mmoL/L.There were significant differences in the level of serum calcium of different days (P ＜ 0.05).On the second and third day,the change of serum calcium were 0.46 (0.10,0.88) mmol/L,0.60 (0.25,0.75) mmol/L,there were no differences.After intravenous disodium pamidronate,the serum calcium level decreased below 3.5 mmol/L in (2.27 ± 0.65) days,and were kept below 3.5mmol/L for 18.45 ± 12.30 days.Conclusions Disodium pamidronate can decrease serum calcium levels in hypercalcemic crisis caused by primary hyperparathyroidism effectively with mild adverse events.

Cytotoxic function of gamma delta (ϒ/δ) T cells against pamidronate- treated cervical cancer cells.

The cytotoxic function of polyclonal expanded ϒ/δ T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The ϒ/δ T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 μM pamidronate. The expansion of ϒ/δ T cells was 15 times more than the non-stimulated cells. Among the expanded ϒ/δ T cells, 47% were Vϒ9/Vδ2 T cells with a purity of 87%. Analyzing the cytotoxic function of ϒ/δ T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on ϒ/δ T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the ϒ/δ T cells to kill cancer cells. The killing ability of ϒ/δ T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that ϒ/δ T cells induce apoptosis in tumor cells. Our study supports the usefulness of ϒ/δ T cells in future development of immunotherapy for cervical cancer.

Efficacy of pamidronate in children with low bone mineral density during and after chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma

BACKGROUND: Reduced bone mineral density (BMD) is a significant sequelae in children receiving chemotherapy for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Reduced BMD is associated with an increased risk for fractures. Pamidronate, a second-generation bisphosphonate, has been used to treat osteoporosis in children. This study evaluated the safety and efficacy of pamidronate in children with low BMD during and after chemotherapy for ALL and NHL. METHODS: Between April 2007 and October 2011, 24 children with ALL and NHL were treated with pamidronate. The indication was a decreased BMD Z-score less than -2.0 or bone pain with a BMD Z-score less than 0. Pamidronate was infused at 1 mg/kg/day for 3 days at 1-4 month intervals (pamidronate group, cases). The BMD Z-scores of the cases were compared with those of 10 untreated patients (control group). Lumbar spine BMDs were measured every 6 cycles using dual energy X-ray absorptiometry and Z-scores were calculated. Bone turnover parameters (25-hydroxyvitamin D, alkaline phosphatase, parathyroid hormone, osteocalcin, and type I collagen c-terminal telopeptide) were analyzed. RESULTS: The median cycle of pamidronate treatment was 12. Increases in BMD Z-scores were significantly higher in the pamidronate group than in the control group (P<0.001). BMD (mg/cm2) increased in all pamidronate-treated cases. Twenty patients who complained of bone pain reported pain relief after therapy. The treatment was well tolerated. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of children with low BMD during and after chemotherapy for ALL and NHL.

Hypercalcemia Refractory to Pamidronate Associated with Metastatic Calcifications in Multiple Organs / 대한내과학회지

Paget's disease of bone (PDB) is a disorder featuring high-level bone turnover associated with the presence of disorganized and immature bone tissue with excessive levels of fibrosis. The risk of deformity is very high. The etiology of PDB is not well understood, but includes both genetic and environmental factors among which is bone trauma. Hypercalcemia can occur as a complication of PDB in patients who are immobilized and dehydrated. However, to date, no case of severe hypercalcemia with metastatic calcifications in multiple organs has been reported in any PDB patient. The drugs of choice for treatment of PDB are bisphosphonates. These drugs effectively suppress bone turnover. Patients with extensive PDB may require higher doses of bisphosphonates, and acquired resistance to a particular bisphosphonate may be overcome by use an alternative drug. Here, we report a case of suspicion of PDB. The patient presented with hypercalcemia and metastatic calcifications and his condition improved dramatically after treatment with zoledronic acid.

Hypercalcemia Refractory to Pamidronate Associated with Metastatic Calcifications in Multiple Organs / 대한내과학회지

Paget's disease of bone (PDB) is a disorder featuring high-level bone turnover associated with the presence of disorganized and immature bone tissue with excessive levels of fibrosis. The risk of deformity is very high. The etiology of PDB is not well understood, but includes both genetic and environmental factors among which is bone trauma. Hypercalcemia can occur as a complication of PDB in patients who are immobilized and dehydrated. However, to date, no case of severe hypercalcemia with metastatic calcifications in multiple organs has been reported in any PDB patient. The drugs of choice for treatment of PDB are bisphosphonates. These drugs effectively suppress bone turnover. Patients with extensive PDB may require higher doses of bisphosphonates, and acquired resistance to a particular bisphosphonate may be overcome by use an alternative drug. Here, we report a case of suspicion of PDB. The patient presented with hypercalcemia and metastatic calcifications and his condition improved dramatically after treatment with zoledronic acid.