Desarrollo de un modelo experimental de osteonecrosis de maxilar asociada al tratamiento crónico con aminobisfosfonatos / Experimental model of osteonecrosis of the jaw associated to chronic treatment with aminobisphosphonates

La osteonecrosis de maxilar asociada a aminobisfosfonatos (BRONJ) constituye un efecto secundario del tratamiento crónico con los más potentes. Un modelo experimental permitiría determinar la patogenia de dicha alteración. La oveja presenta características orales y del metabolismo óseo similar al humano y permite realizar manipulaciones bucales. Se evaluaron cambios clínicos, remodelación ósea y masa ósea maxilar en ovejas hembras adultas tratadas con zolendronato (ZOL), durante 22 meses y utilizando dosis equivalente al tratamiento de neoplasias. Seis ovariectomizadas (OVX) recibieron ZOL; 5 OVX y 4 SHAM (control) recibieron solución fisiológica. Al inicio, 4 y 22 meses se evaluó calcemia, fosfatemia, crosslaps (CTX) y fosfatasa alcalina ósea. Al final, se evaluó contenido mineral óseo de la hemimandíbula superior (CMO: mg/cm2). Al final del estudio, CTX disminuyó significativamente en ZOL (p<0,05) sin diferencias entre SHAM y OVX. En maxilar, los contenidos de Ca y P (g/g tejido) y CMO (g/cm2 ) disminuyeron en OVX vs. SHAM (p<0,05) y solo Ca y CMO respecto de ZOL (p<0,05). ZOL incrementó el contenido de Ca y CMO, mientras que el de P permaneció significativamente disminuido respecto de SHAM. La sobrevida en SHAM y OVX fue del 100% y en ZOL 77% (2 muertes); 2 ovejas del grupo ZOL presentaron necrosis de maxilar. Conclusiones: fue posible obtener desarrollo de BRONJ por tratamiento crónico con ZOL, el cual redujo notablemente la resorción y, según la relación Ca/P, posiblemente haya afectado la mineralización ósea. (AU)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of chronic treatment with the most powerful aminobisphosphonates (BPs). An experimental animal model would allow to determine the pathogenesis of this complication. Ewes exhibit similar oral cavity characteristics and bone metabolism as humans, and they are suitable for oral cavity interventions. We examined herein the clinical manifestations, bone remodeling status, and maxillary bone mass in adult female ewes treated with zoledronate (ZOL) for 22 months. Six ovariectomized (OVX) ewes received ZOL; and 5 OVX and 4 SHAM animals received saline solution. At the start of the experiment, and at the 4 and 22 month-time points serum Ca, P, crosslaps (CTX), and bone alkaline phosphatase were measured. Bone mineral content (BMC) of the superior hemimandible was measured at the end of the experiment. At this time point, CTX was significantly decreased only in the ZOL group (p<0.05). Ca and P content (g/g tissue) and BMC in the mandible were significantly decreased in the OVX group compared to SHAM animals (p<0.05) and only Ca content and BMC were decreased when compared to ZOL (p<0.05). ZOL treatment increased the Ca content and BMC, whereas the P content remained low compared to the SHAM group (p<0.05). All ewes from the SHAM and OVX groups and 77% of the animals from the ZOL group survived until the end of the experiment, whereas two ewes of ZOL group exhibited BRONJ. Conclusion: under our experimental conditions, it was possible to induce BRONJ by the chronic ZOL administration, which in turn induced a high reduction in bone resorption as well as possibly impaired bone mineralization, based on the Ca/P ratio in the mandible. (AU)

Osteoporosis: parte II: en enfermedades hepáticas y del tubo digestivo / Osteoporosis: part II: in liver and digestive tract diseases

The present review addresses liver and gastrointestinal diseases that are more frequently associated to osteopenia and osteoporosis. For each disease, we describe the prevalence and physiopathology of these bone metabolism conditions. The purpose is to create awareness of this scenario and prompt early analysis if these patients, and in other cases, to provide prophylaxis and treatment of these disorders.

En esta revisión se abordan las enfermedades hepáticas y del tubo digestivo que con mayor frecuencia se asocian a osteopenia y osteoporosis. En cada patología describimos la prevalencia y fisiopatología de estas afecciones del metabolismo óseo. El objetivo es dar a conocer esta realidad e inducir a que estos pacientes sean estudiados precozmente, en otros casos aplicar la profilaxis y tratar estos desórdenes.

Factors Related to Decreased Bone Mineral Density in Childhood Cancer Survivors

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 +/- 1.39 vs -0.43 +/- 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

Vitamin D deficiency in HIV-infected individuals: one more risk factor for bone loss and cardiovascular disease? / Deficiência de vitamina D em indivíduos infectados pelo HIV: mais um fator de risco para perda óssea e doença cardiovascular?

The epidemiological profile of the HIV virus has undergone substantial modifications with advances in antiretroviral therapy. There has been a sharp decline in morbi-mortality levels of HIV-infected patients, which has resulted in higher survival rates. The HIV seropositive population is living longer and more exposed to chronic complications caused by the disease itself and the prolonged use of antiretrovirals. Initially, metabolic alterations were reported, increasing cardiovascular disease risk. Subsequently, damage on bone metabolism was related. Vitamin D insufficiency has now reached epidemic proportions, even in healthy individuals living in the tropics. Recent data suggest the hypovitaminosis D association with metabolic syndrome, immune diseases, diabetes and hypertension. Little is known regarding the effects of HIV/Aids and its treatment on the metabolism of vitamin D. In HIV-positive patients, factors linked to the virus itself and the use of antiretrovirals may be added to the other causes of hypovitaminosis D.

O perfil epidemiológico da infecção pelo vírus HIV vem sofrendo grandes modificações com os avanços na terapia antirretroviral. Houve uma queda expressiva na morbi-mortalidade do paciente infectado pelo HIV e, por conseguinte, aumento da sobrevida. A população soropositiva está envelhecendo e mais exposta às complicações da cronificação da doença e ao uso prolongado dos antirretrovirais. Inicialmente foram descritas alterações metabólicas que contribuem para um aumento no risco de doença cardiovascular. Em seguida, surgiram relatos de danos ao metabolismo ósseo. A deficiência de vitamina D tem atingido proporções epidêmicas envolvendo até mesmo indivíduos saudáveis em regiões tropicais. Dados recentes sugerem sua associação com síndrome metabólica, doenças imunes, diabetes e hipertensão. A doença HIV/Aids e a ação dos antirretrovirais no metabolismo da vitamina D ainda permanecem pouco conhecidas. Em pacientes HIV positivos, fatores ligados ao próprio vírus e ao uso dos antirretrovirais podem estar adicionados às demais causas de hipovitaminose D.

Potential protective effect of L-Arginine on cyclosporine A induced osteopenia in adult albino rats

This study aimed to assess the possible toxic effect of cyclosporine A [CsA] on bone and the potential protective effect of L-arginine on CsA-induced osteopenia. The study was conducted on 120 adult male albino rats divided into eight equal groups: Group I [negative control], group II [distilled water], group III [corn oil], group IV [L-arginine, low dose], group V [L-arginine, high dose], group VI [CsA], group VII [L-arginine, low dose + CsA] and group VIII [L- arginine, high dose + CsA]. The duration of the study was six weeks, then the level of urinary deoxypyridinoline [Dpd] and N- terminal telopeptide [NTx] [markers of bone resorption], serum calcium, osteocalcin and bone specific alkaline phosphatase [BSALP] [markers of bone formation] were measured. Also, bone mineral density [BMD] of spine using dual energy X-ray absorptiometry [DEXA] was measured. The results showed that CsA had an osteopenic effect and L-arginine provoked a significant protective effect

Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000.

Epidemiological studies during 1963-1997 were conducted in 45,725 children exposed to high intake of endemic fluoride in the drinking water since their birth. Children with adequate (dietary calcium > 800 mg/d) and inadequate (dietary calcium < 300 mg/d) calcium nutrition and with comparable intakes of fluoride (mean 9.5 +/- 1.9 mg/d) were compared. The toxic-effects of fluoride were severe and more complex and the incidence of metabolic bone disease (rickets, osteoporosis. PTH bone disease) and bony leg deformities (genu valgum, genu varum, bowing, rotational and wind-swept) was greater (> 90%) in children with calcium deficiency as compared to < 25% in children with adequate calcium who largely had osteosclerotic form of skeletal fluorosis with minimal secondary hyperparathyroidism. The syndrome of skeletal fluorosis and associated metabolic bone disease and deformity is a unique clinical entity classified as a variant of osteosclerotic form of skeletal fluorosis. This syndrome chiefly results from the biological impact of excess fluoride, low calcium, high PTH and 1,25 (OH)2D3 separately and through their interactions on bone structure and metabolism as studied by radiology, bone scanning, bone histomorphometry and relevant metabolic and endocrine laboratory investigations. Metabolically active and vascular bones of children accumulate fluoride at faster and greater rate than adults (at the sites of active growth). In calcium deficient children the toxic effects of fluoride manifest even at marginally high (> 2.5 mg/d) exposures to fluoride. Fluoride toxicity also exaggerates the metabolic effects of calcium deficiency on bone. The findings strongly suggest that children with calcium deficiency rickets reported in the literature should be re-investigated for possible fluoride interactions. Deep bore drinking water supply with fluoride < 0.5 ppm and improvement of calcium nutrition provide 100% protection against the toxic effects of fluoride and are recommended as the cost effective and practical public health measures for the prevention and control of endemic fluorosis.