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Vitamin D is essential for bone metabolism and has gained popularity since the general population is now more aware of its benefits. Unfortunately, the availability of unregulated vitamin D formulations without prescription increases the risk of inadvertently ingesting excessive doses of vitamin D. Reports of pediatric cases of vitamin D toxicity are scarce in the world literature. We present the case of a 4-years 9-months old boy from a rural town with vitamin D intoxication secondary to ingestion of seven oral vials containing each of them 600,000 Units of cholecalciferol for a period of 8 months. It is important to educate general population about the risks of ingesting vitamin D without medical prescription. In our patient, the most effective treatment strategy was the use of pamidronate.

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Introduction: Chronic primary osteomyelitis (CPO) is a rare disease, defined as a chronic inflammatory process involving cortical and medullary bone. In the maxillofacial region, it mainly affects the mandible, with a predilection for females in a wide age range, with unknown etiology or defined treatment protocol. Objective: The objective of this article is to report a case of the rare disease Chronic Primary Osteomyelitis, focusing on its cli-nical, radiographic, and histopathological characteristics, and to discuss the nomenclature for differential diagnosis while comparing with other osteomyelitis. Case Report: MLP patient, 53 years old, female, leukoderma, was admitted at the Maxillofacial Surgery and Traumatology Service of the University Hospital of USP referred from another service and reported of severe pain and swelling in the face for approximately 1 .5 year. On cli-nical examination, he presented edema 1+/4+ in the lower third of the right hemiface, sensitive to palpation, trismus, lower lip paresthesia, no evidence of infectious odontogenic focus, increased volume or intraoral secretion. The patient was submitted to an incisional biopsy, computed tomography and scintigraphy, which showed an sclerotic pattern and increased uptake in the mandible, respectively. After months of antibiotic therapy with no results, the patient was initially submitted to 20mg of Prednisone with regression up to 5mg and two doses of 60mg of Pamidronate which resulted in remission of pain, edema and trismus. Until the publication of this article, the patient had no recurrence of the symptoms, totalizing 6 years of follow up. Conclusion: CPO is a rare and challenging diagnosis disease. Prednisone was effective to edema and trismus decreasement and Pa-midronate for pain control, however more studies are necessary to determine a definitive treatment for this condition. (AU)

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Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum (L. infantum). Currently, there are no vaccines and/or prophylactic therapies against VL, and the recentpharmacological approaches come from the drug repositioning strategy. Here, we evaluated the anticancer drug pamidronate (PAM) to identify a new therapeutic option for the treatment of human VL. We assessed its in vitro antileishmanial activity against the promastigote and amastigote forms of L. infantum by evaluating cell cytotoxicity. The antileishmanial and immunomodulatory activities were assessed using human peripheral blood leukocytes ex vivo. PAM induced the formation of vacuoles in the cytoplasm of the promastigotes and alterations in the morphology of the kinetoplast and mitochondria in vitro, which indicates anti-promastigote activity. PAM also reduced the number of infected macrophages and intracellular amastigotes in a concentration-dependent manner, with cell viability above 70%. In ex vivo, PAM reduced the internalized forms of L. infantum in the classical monocyte subpopulation. Furthermore, it enhanced IL-12 and decreased IL-10 and TGF-ß by monocytes and neutrophils. Increased IFN-γ and TNF levels for CD8- and CD8+ T lymphocytes and B lymphocytes, respectively, were observed after the treatment with PAM, as well as a reduction in IL-10 by the lymphocyte subpopulations evaluated. Taken together, our results suggest that PAM may be eligible as a potential therapeutic alternative for drug repurposing to treat human visceral leishmaniasis.

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The aim of this review was to describe orbital inflammation secondary to aminobisphosphonates by analyzing demographic data, clinical presentation, and treatment of the disease. This is a narrative literature review. The search was performed using databases such as Ovid/MEDLINE and COCHRANE. The searches were limited to papers in the English language. We found 43 cases of orbital inflammation due to aminobisphosphonates. Zoledronate was the drug most associated with orbital side effects. Clinical presentation was evident by unilateral involvement (89%), palpebral edema (88%), conjunctival congestion (81%), chemosis (79%), ocular pain (77%), ocular motility impairment (65%), proptosis (56%), and blurred vision (39%). It can affect both eyes (11%) and is accompanied by anterior uveitis (23%). Orbital inflammation secondary to aminobisphosphonates is a severe side effect. Clinically, it cannot be distinguished from idiopathic inflammation of the orbit. Therefore, it is important to rule out previous drug exposure. Timely treatment is vital to expect a favorable outcome, with systemic corticosteroids being the treatment of choice.

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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.

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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.

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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.

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.

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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.

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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.

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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.

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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)

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Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

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Bisphosphonates are osteoclast inhibitors, currently being used in oncology to prevent or delay bone morbidity in cancer. Oral and intravenous formulations of bisphosphonates have been found to be efficacious in preventing skeletal-related events such as bone pain, pathologic fractures, spinal cord compression and hypercalcemia of malignancy, in patients with bone metastatic breast cancer. Bisphosphonates are also used to prevent bone loss associated with anti-estrogen therapy using aromatase inhibitors. In addition to its role in preventing bone resorption, several pre-clinical studies have noted an anti-tumor role as well. Recent research effort has particularly focused on investigating an adjuvant role for bisphosphonates in early breast cancer. Recently, few randomized trials have found a beneficial effect for adjuvant use of the aminobisphosphonate, zoledronate, in older patients who are post-menopausal. This review article will summarize the various clinical studies investigating the role of bisphosphonates in breast cancer.

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Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

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Se ha efectuado una revisión de los trabajos sobre la fisiopatología del MM y sobre el tratamiento de las lesiones osteoporóticas que se presentan en casi todos los casos. Es sabido que los bifosfonatos son sumamente efectivos por lo que se comentan los actuales esquemas de tratamiento tomando en cuenta los recientes consensos. Hay un acuerdo prácticamente unánime en la eficacia del pamidronato y el zoledronato endovenosos aplicados mensualmente durante dos años, siendo aceptado el uso del clodronato oral en Europa pero no en EE.UU. Aunque mejorarían la calidad de la sobrevida, los bifosfonatos no la prolongarían. Se refieren las precauciones que habría que tomar para evitar la osteonecrosis de mandíbula, una complicación de las dosis altas de bifosfonatos que se ha comunicado con mayor frecuencia durante los últimos años. Se destaca la importancia de la consulta odontológica frecuente y del permanente cuidado dental.

The aim of this review is to discuss recent findings in the physiopathology and treatment of osteoporotic lesions present in almost all patients with MM. The efficacy of bisphosphonates is well known, so we summarize the current treatment schedules according to the most recent consensus. Pamidronate and Zoledronate are equally effective and universally accepted. They should be administered intravenously on a monthly basis for two years. Oral clodronate is accepted in Europe but not in USA. Even if bisphosphonates provide a better quality of life, they do not increase survival. Because osteonecrosis of the jaw has been repeatedly reported after high doses of bisphosphonates, we discuss the necessary precautions to prevent this condition emphasizing frequent dental care and examinations.

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A osteogênese imperfeita (OI) é uma doença genética caracterizada por fragilidade e deformidades ósseas, fraturas de repetição e baixa estatura. Esses desfechos se devem a mutações genéticas que ocasionam a deficiência na produção de colágeno tipo I. Apresentamos aqui o caso de um paciente de 9 anos, com diagnóstico de OI tipo IV, que interna para realização de novo ciclo de pamidronato dissódico. O caso demonstra a importância do tratamento nutricional da OI, que aborda principalmente a ingestão de cálcio e vitamina D, evitando seus fatores antinutricionais.

Osteogenesis imperfecta (OI) is a genetic disease characterized by weakness and bone deformities, fractures of repetition and short stature. These outcomes are due to genetic mutations that cause deficiency in the production of collagen type I. We report the case of a 9-year-old male patient, diagnosed with OI type IV, hospitalizated to perform a new cycle of pamidronate. This case demonstrates the importance of nutritional treatment of OI, which mainly deals with dietary intake of calcium and vitamin D, avoiding their antinutritional factors.

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Introdução. A osteogênese imperfeita é doença congênita rara, de origem genética, decorrente de distúrbios na síntese do colágeno tipo 1, caracterizada por graus variados de fragilidade e deformidade óssea. Objetivo. Avaliar o impacto da terapia com pamidronato sobre o número de fraturas, a dor óssea, a motricidade funcional e a prática de atividades físicas em pacientes pediátricos com osteogênese imperfeita. Método. Estudo retrospectivo dos prontuários de sessenta pacientes com osteogênese imperfeita, acompanhados no Hospital Universitário de Brasília. Foram tabelados e analisados os dados referentes ao número de pacientes com fraturas, dores ósseas, prática regular de atividades físicas e à motricidade funcional antes e depois do início da terapia com pamidronato. Resultados. Das 60 crianças avaliadas (30 do sexo feminino) com osteogênese imperfeita, 14 foram do tipo I,33 do tipo III e 13 do tipo IV. A média de idade foi 8,8 ± 4,5 anos e média de idade ao diagnóstico, 3,1 ± 4,1 anos.Desses, 55 ingressaram no protocolo para recebimento do pamidronato. Depois do início da terapia, o número de doentes que tiveram fraturas reduziu-se de 55 para 17; o número de casos com dores ósseas constantes decresceu de 39 para 8; o de pacientes com prática regular de atividade física subiu de 12 para 38 e todos tiveram melhora damotricidade funcional. Todas essas diferenças foram estatisticamente ignificativas. Conclusão. O uso de pamidronato está relacionado à diminuição estatisticamente significativa de fraturas e de dores ósseas, à melhora da motricidade funcional e à regularidade de bons desempenhos físicos em indivíduos com osteogênese imperfeita, com repercussão positiva em sua integração social.

Introduction. Osteogenesis imperfecta is a rare congenital disease, of genetic inheritance, secondary to disturbanceson type 1 collagen synthesis, and characterized by a wide spectrum of bone fragilities and deformities. Objective. To evaluate the impact of pamidronate therapy on the number of fractures, bone pain complaints, functional motor mobility and on the practice of physical activities among pediatric patients with osteogenesis imperfecta. Method. Retrospective study of the records from the sixty patients with osteogenesis imperfecta followed at Hospital Universitário de Brasília. The data relating to the number of patients presenting fractures, bone pain andwith customary physical activities and to their functional mobility before and after pamidronate therapy were set and analyzed. Results. From the 60 children (30 females) with osteogenesis imperfecta, 14 were type I, 33 type III and 13 type IV. Mean age was 8.8 ± 4.5 years and mean age at diagnosis was 3.1 ± 4.1 years. Fifty-five patients were admitted to the pamidronate protocol. After the therapy has started, the number of patients presenting fractures decreased from55 to 17, presenting constant bone pain went from 39 to 8, with customary physical activities increased from 12 to 38 and all of them presented optimized functional motor mobility. All these differences were statistically significant. Conclusion. The use of pamidronate is related to a statistically significant decrease in fractures and bone pains and improvement on functional mobility and on regular practice of physical activity among patients with osteogenesis imperfecta, leading to a positive repercussion on their social integration.

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BACKGROUND: Limited information is available about long-term pamidronate treatment in adults with fibrous dysplasia (FD) of bone. OBJECTIVE: The aim of this case series was to report the clinical outcomes and the biochemical and densitometric findings in a group of young adult patients with polyostotic FD treated for ≥3 years with IV pamidronate. METHODS: Pamidronate was administered every 6 months (60 mg/d for 3 days) for 2 years. Thereafter, treatment was individualized. Pamidronate was administered at shorter or longer intervals based on response. Bone pain, radiography, serum bone alkaline phosphatase (BALP) activity, and urinary C-terminal cross-linking telopep-tide of type I collagen (CTX-I) concentration were assessed for a mean of 7 years. Bone mineral density (BMD) of FD areas (FDas) and contralateral areas (CLas) were measured at baseline and at 12 and 24 months. Data were collected prospectively. RESULTS: Seven patients (5 women, 2 men; mean [SD] age, 31.0 [7.2] years [range, 22-43 years]) were included in the study. Patients received IV pamidronate for a mean of 6.9 years (median, 7.1 years [range, 3.7-10.9 years]). Pamidronate was associated with a reduction in bone pain and a significant reduction in BALP in all patients at the end of follow-up (P < 0.02). The mean reduction from baseline in CTX-I concentration (measured in 3 patients) was 56%; this difference was not significant. Mean BMD values of FDas were significantly increased at 12 months (by 5.9%; P < 0.05) compared with baseline; but was not significantly increased at 24 months (7.3%), probably reflecting a higher dispersion of values due to individual responses to treatment. No significant changes were observed in CLa BMDs. Mean BMD of FDa had a numerically lower decrease of 15.3% compared with CLa at baseline; these decreases with pamidronate were 10.8% at 12 months (P = NS) and 9.3% at 24 months (P < 0.05). Refilling of osteolytic lesions was not observed. CONCLUSIONS: These patients with FD of bone treated with IV pamidronate long term had improvement in bone pain and BMD. The effectiveness of individualized pamidronate administration in the long-term treatment of FD in adult patients should be investigated in blinded controlled trials.

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Os bisfosfonatos são comumente utilizados no tratamento do mieloma múltiplo e em outras neoplasias com metástases ósseas. Geralmente são bem tolerados, entretanto osteonecrose de mandíbula é um efeito adverso recentemente relatado com uso de bisfosfonatos endovenosos. Relata-se um caso de osteonecrose de mandíbula em paciente submetido ao tratamento de mieloma múltiplo com quimioterapia e pamidronato endovenoso.

Bisphosphonates are commonly used in the treatment of multiple myeloma and other bone metastatic neoplasias. They are usually well tolerated; however osteonecrosis of the jaw is a recently reported side effect seen with the use of parenteral bisphosphonates. We report a case of osteonecrosis of the jaw in a patient treated for multiple myeloma with chemotherapy and parenteral pamidronate.

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BACKGROUND: Intravenous disodium pamidronate has been described in the treatment of several osteopathies. Although tolerability has been found to be good in clinical trials, some mild to serious adverse events (AEs) have been reported. OBJECTIVES: The aims of this study were to analyze the toelrability of IV pamidronate in patients being treated for osteoporosis and other metabolic osteopathies and to describe particular patients with relative contraindications, because such cases are not commonly seen in daily clinical practice. METHODS: We performed a retrospective analysis of patients with different osteopathies who were administered IV infusions of pamidronate at doses ranging from 15 to 90 mg/infusion and 15 to 900 mg/year. The study was conducted in patients who had received treatment at the Institute of Metabolic Investigations, University of Salvador, Buenos Aires, Argentina, between January 1995 and December 2003. To rule out dose-related AEs, a comparison was made between patients who received fewer IV infusions and had cumulative doses of 120 to 180 mg/y (less frequent administration [LFA] group) and those patients who received regular infusions and had cumulative doses of >180 mg/year (frequent administration [FA] group). To confirm data obtained from medical records and to assess the occurrence of AEs, attempts were made to interview all patients by phone. The following information was verified for each patient included in the study: the reason for treatment, documented evidence of current diagnostic criteria, and whether the dose administered was adequate to treat the patient's condition. RESULTS: Six hundred eight patients (464 [76.3%]women, 144 [23.7%]men; mean [SD] age, 69 [10] years) with various osteopathies (osteoporosis, 367 [60.4%] of the patients; Paget's disease, 172 [28.3%]; Sudeck's disease, 63 [10.4%]; multiple myeloma, 3 [0.5%]; and bone metastases, 3 [0.5%]) were administered a total of 2933 IV infusions of pamidronate during the study period. We were able to confirm the clinical records of 69.4% (422/608) of the patients by telephone survey; 29.9% (124/415) of those patients experienced extraskeletal AEs (most commonly fever and flu-like symptoms [eg, headache, malaise, fatigue, chills, and asthenia]). The percentage of patients reporting AEs was significantly higher for the LFA group than that of the FA group (91.2 vs 19.5; P < 0.001), although factors other than the frequency of treatment might have had a bearing on this finding. All AEs were mild and transient in both groups of patients, and there were no reports of jaw osteonecrosis in either group. It should be noted that although LFA patients received lower doses of pamidronate per infusion than the FA group, they had higher cumulative doses/year. Biochemical variables for the entire study population were compared with baseline measurements, and no significant changes in mean values were observed. Both serum calcium and 25-hydroxy vitamin D levels remained within normal ranges. On the other hand, there was a transient decrease in white blood cell count (WBCC) in 73 (12.0%) patients, and leukopenia was observed in 8 (1.3%) patients. However, 5 of the 6 patients who were leukopenic at the beginning of treatment had normal WBCCs during follow-up. Platelet count decreased significantly in 20 (3.3%) patients, and 5 (0.8%) patients developed thrombocytopenia. Serum creatinine (sCreat) levels increased significantly in 91 (15.0%) patients. This increase was transient and within normal limits (0.6-1.2 mg/dL) in 79 (86.8%) of those patients but persistent in the other 12 (13.2%), all of whom received higher doses of pamidronate or had other risk factors for renal failure such as advanced age, diabetes, multiple myeloma, or an obstructor disease. Baseline sCreat level for 7 of these 12 patients was >1.20 mg/dL. CONCLUSIONS: Pamidronate administered IV was well tolerated when used for treating osteoporosis or other metabolic osteopathies in our study population. The clinical AEs observed with IV pamidronate administration were not serious and hematologic changes were mild, transient, and not associated with dose, time of treatment, or any particular underlying disease. An increase in sCreat level was the most frequent biochemical complication and was found in patients with additional risk factors for renal failure and particular diseases. Whether certain patients with risk factors for osteoporosis may require even fewer IV administrations of the drug is an issue that remains to be elucidated.