Deprivación andrógenica en cáncer de próstata y riesgo de fractura a largo plazo / Androgen deprivation in prostate cancer and the long-term risk of fracture

Objetivos: Determinar el porcentaje de pérdida de masa ósea y el riesgo de fractura inducido por la terapia de deprivación androgénica en pacientes con cáncer de próstata. Material y métodos: Estudio prospectivo en 2 fases. En la primera se recogieron variables demográficas, FRAX(R), densidad mineral ósea y fracturas clínicas antes de iniciar la terapia y hasta un año después de finalizada. En la segunda se realizó una entrevista telefónica una media de 8,5 años después del inicio del estudio para evaluar nuevas fracturas. Resultados: Se incluyeron 150 pacientes con una edad media de 67 años y duración media de la terapia de 24 meses. Antes del inicio del tratamiento 62 pacientes (41%) presentaban osteoporosis o baja masa ósea en la densitometría. Después del primer año de tratamiento la densidad mineral ósea descendió una media de 3,7% y 2,1% en la columna lumbar y el cuello femoral, respectivamente. Al final del segundo y tercer año el porcentaje de pérdida fue menor. Durante la primera fase del estudio 4 pacientes (2,7%) sufrieron una fractura. En la entrevista telefónica a 80 pacientes (53%) solo uno había sufrido una fractura. Conclusiones: En los pacientes con cáncer de próstata y terapia de deprivación androgénica la mayor pérdida ósea se produce durante el primer año. Cuando el tratamiento no supera los 2 años el riesgo absoluto de fractura es bajo, y la fractura clínica infrecuente a corto y a largo plazo

Objectives: To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. Material and methods: Prospective study in 2 phases. In the first phase, demographic variables, FRAX(R), bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. Results: We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. Conclusions: In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term

In vitro evaluation of adhesion/proliferation of human gingival fibroblasts on demineralized root surfaces by toluidine blue O in antimicrobial photodynamic therapy.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) in Dentistry has important effects as bacterial destruction in areas with periodontal disease. Some dyes applied in aPDT could present low pH and, consequently, result in tooth demineralization. This study evaluated demineralization produced by aPDT with toluidine blue O (TBO) at low pH and analyzed adhesion/proliferation of human gingival fibroblasts (HGF). METHODS: In the 1st phase, bovine enamel and root dentin fragments received 2 treatments: PDT4 group (TBO-100 µg/ml-pH 4-60s) plus laser (660 nm, 45 J/cm(2), 1.08 J, 30 mW, 30 s, spot 0.024 cm(2), 1.25 W/cm(2), sweeping, non-contact) and CA group (citric acid plus tetracycline-pH 1-180 s). Surface hardness loss and tooth wear were statistically analyzed (Student's t test, ANOVA/Tukey, p<0.05). In the 2nd phase, human dentin fragments were divided in C (control group-scaling and root planing), PDT4 and CA. HGF (10(4), 5th passage) were cultured on these fragments for 24, 48 and 72 h and counted in scanning electron microscopy photographs. Number of HGF was analyzed using repeated-measures ANOVA and Tukey (p<0.05). RESULTS: Percentage of surface hardness loss was similar in dentin for PDT4 (71.5%) and CA (76.1%) (p>0.05) and higher in enamel for CA (68.0%) compared to PDT4 (34.1%) (p<0.05). In respect to wear, no difference was found between PDT4 (dentin: 12.58 µm, enamel: 12.19 µm respectively) and CA (dentin: 11.74 µm and enamel: 11.03 µm) (p>0.05). Number of HGF was higher after 72 h in CA group (2.66, p<0.05) compared to PDT4 (2.2) and C (1.33). CONCLUSION: PDT4 is not as aggressive as CA for enamel. However, dentin demineralized promoted by PDT4 does not stimulate HGF adhesion and proliferation as CA.

Efecto del tratamiento del carcinoma de mama y del carcinoma de próstata sobre la masa ósea / Treatment effect of breast cancer and prostate cancer on bone

Los inhibidores de la aromatasa utilizados en el tratamiento del carcinoma de mama y la terapia de deprivación androgénica empleada en el carcinoma de próstata inducen una pérdida de masa ósea y un aumento de la incidencia de fracturas, motivo por el cual es importante la detección precoz de aquellos pacientes con mayor riesgo de sufrir fracturas osteoporóticas. En este artículo realizamos una revisión de los tratamientos disponibles y de cuándo están indicados para prevenir la aparición de osteoporosis y de fracturas osteoporóticas en este grupo de pacientes (AU)

Aromatase inhibitors are used in the treatment of breast cancer and androgen deprivation therapy isused in prostate cancer. Both of them induce bone loss and increase fracture incidence. Early detection isimportant for patients with increased risk of osteoporotic fractures. In this article we review theavailable treatments and their indication to prevent the onset of osteoporosis and osteoporotic fracturesin this patient group (AU)

Análisis geométrico de la arquitectura trabecular de un hueso de bovino durante el proceso inducido de desmineralización / Geometric analysis of the trabecular architecture in a bovine bone during the process of induced demineralization

La masificación de la radiología digital ha hecho posible el estudio de diferentes patologías mediante imágenes de alta calidad diagnóstica. Existen diferentes patologías que afectan al tejido óseo, y que producen pérdida del mineral(1). Aquellas patologías se caracterizan por la pérdida de la arquitectura trabecular y un adelgazamiento de la cortical(7), visibles en la radiología. Aquellos cambios llevan al paciente a caer en el riesgo de sufrir futuras fracturas(8), por lo que se considera importante realizar un análisis de la geometría de las trabéculas ante este tipo de patología, con el fin de prever riesgos de fractura. Material y Métodos. Para realizar este estudio, se escogió un fémur de bovino(19). Este fue sumergido en ácido acético al 4 por ciento, con el fin de producir su desmineralización. Se le realizó una medición cada 24 horas mediante la adquisición de imágenes radiológicas, que fueron obtenidas con un equipo digital directo hasta observar cambios radiológicos evidentes en la población trabecular. Las imágenes fueron evaluadas mediante un software de libre acceso llamado ImageJ®(23), realizando mediciones trabeculares mediante la herramienta ROI, y se adquirieron los valores de área, perímetro y circularidad. Resultados. En las 10 trabéculas estudiadas se observaron y cuantificaron cambios en la arquitectura trabecular, aumentando el área en un 124 por ciento, el perímetro en un 53 por ciento y la circularidad se mantuvo en promedio constante. Conclusiones: Mediante la radiología digital, es posible evaluar la arquitectura trabecular mediante parámetros geométricos, los cuales nos indican que existen cambios muy pequeños a lo largo del tiempo. Se observó un aumento de tamaño en las trabéculas, pero sin pérdida de su forma.

Introduction. The mass use of digital radiology has made possible the study of different pathologies through high quality diagnostic images. There are different diseases that affect bone tissue and which produce mineral loss (1). Those diseases are characterized by loss of trabecular architecture and cortical thinning (7), visible in radiology. Those changes lead the patient to suffer the risk of future fractures (8), therefore it is considered important to analyze the geometry of the trabeculae in this kind of pathology in order to anticipate fracture risk. Material and Methods. For this study, a bovine's femur was chosen(19). This was immersed in 4 percent acetic acid to produce demineralization. Measurement was performed (in Clinica Alemana Santiago) every 24 hours by radiological imagings, which were obtained with digital radiology (DR) to observe obvious radiological changes in trabecular population. The images were evaluated by a freely available software called ImageJ® (23), by performing Trabecular measurements using the ROI tool, acquiring the values of area, perimeter and circularity. Results. In the 10 trabeculae studied, we observed and quantified changes in trabecular architecture, increasing the value of average area in 124 percent, perimeter in 53 percent and no change in circularity during the demineralization process. Conclusions. With digital radiography, it is possible to evaluate the trabecular architecture using geometric parameters, which indicate that there are very small changes over time. An increase in size of the trabeculae was observed, trabeculae was observed, but without loss of shape.

Adherence to treatment with selective serotonin reuptake inhibitors and the risk for fractures and bone loss: a population-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are suspected of increasing the risk of bone loss and osteoporotic fractures. OBJECTIVE: The aim of this study was to investigate the association between adherence to SSRI treatment and the risk of bone loss-related events. METHODS: The data used in this retrospective cohort study are part of the ongoing medical documentation routinely collected in a large health maintenance organization in Israel. Specifically, we used the information collected between January 2004 and April 2010. The study cohort included 10 621 women who were new users of SSRIs. Bone loss-related events were defined as fractures or initiation of bisphosphonate treatment. Adherence level was assessed by calculating the proportion of days covered (PDC) with an SSRI from the date of first dispensed SSRI (index date) to the end of follow-up and was categorized as low (PDC ≤20%), intermediate (PDC 21-79%) and high (PDC ≥80%). To validate the study model, we conducted a similar analysis on patients using antiepileptic drugs, which are known to be positively associated with an increased risk of osteoporotic fractures. RESULTS: Higher adherence to SSRI treatment was significantly associated with an increased risk of bone loss-related events in a dose-response manner. The adjusted hazard ratio for bone loss-related events adjusted for age, physician visits and body mass index in patients who were covered with an SSRI for 21-79% of the time and 80% or more of the time was 1.15 (95% CI 0.97, 1.37) and 1.40 (95% CI 1.14, 1.73) compared with patients who were covered for less than 21% of the follow-up period. CONCLUSION: Exposure to SSRI treatment is associated with an increased risk of bone loss-related events. Further studies are required to determine the causality of the association and its relevance to the clinical use of SSRIs.

A SNP in steroid receptor coactivator-1 disrupts a GSK3ß phosphorylation site and is associated with altered tamoxifen response in bone.

The coregulator steroid receptor coactivator (SRC)-1 increases transcriptional activity of the estrogen receptor (ER) in a number of tissues including bone. Mice deficient in SRC-1 are osteopenic and display skeletal resistance to estrogen treatment. SRC-1 is also known to modulate effects of selective ER modulators like tamoxifen. We hypothesized that single nucleotide polymorphisms (SNP) in SRC-1 may impact estrogen and/or tamoxifen action. Because the only nonsynonymous SNP in SRC-1 (rs1804645; P1272S) is located in an activation domain, it was examined for effects on estrogen and tamoxifen action. SRC-1 P1272S showed a decreased ability to coactivate ER compared with wild-type SRC-1 in multiple cell lines. Paradoxically, SRC-1 P1272S had an increased protein half-life. The Pro to Ser change disrupts a putative glycogen synthase 3 (GSK3)ß phosphorylation site that was confirmed by in vitro kinase assays. Finally, knockdown of GSK3ß increased SRC-1 protein levels, mimicking the loss of phosphorylation at P1272S. These findings are similar to the GSK3ß-mediated phospho-ubiquitin clock previously described for the related coregulator SRC-3. To assess the potential clinical significance of this SNP, we examined whether there was an association between SRC-1 P1272S and selective ER modulators response in bone. SRC-1 P1272S was associated with a decrease in hip and lumbar bone mineral density in women receiving tamoxifen treatment, supporting our in vitro findings for decreased ER coactivation. In summary, we have identified a functional genetic variant of SRC-1 with decreased activity, resulting, at least in part, from the loss of a GSK3ß phosphorylation site, which was also associated with decreased bone mineral density in tamoxifen-treated women.

Cadmium is more toxic on volume bone mineral density than tissue bone mineral density.

It has been showed that Cd induces low areal bone mineral density, but we do not know the effect of Cd on cubic bone density. This study was aimed to investigate the effects of Cd on volumetric bone mineral density (VBMD) and tissue bone mineral density (TBMD) in male rats. Twenty-four Sprague-Dawley male rats were randomly divided into four groups that were given cadmium chloride by subcutaneous injection at doses of 0, 0.1, 0.5, and 1.5 mg/kg body weight for 8 weeks, respectively. Then, microcomputed tomography scanning was performed on the proximal tibia, and region of interest was reconstructed using microview software. The VBMD, bone volume fraction of rats treated with 1.5 mg Cd/kg, were significantly decreased compared to control (p < 0.01). The trabecular numbers of rats exposed to Cd were all significantly decreased relative to control (p < 0.05). The trabecular separation of rats treated with 1.5 mg Cd/kg was obviously increased compared to control (p < 0.01). However, Cd had no obvious influence on TBMD. Cd induced low VBMD but not TBMD; Cd effect on bone may be related with trabecular bone loss but not with trabecular bone demineralization.

Managing bone health with zoledronic acid: a review of randomized clinical study results.

AIM: To systematically review randomized, controlled clinical trials for managing osteoporosis, cancer treatment-induced bone loss, and bone metastases from breast cancer using zoledronic acid (ZOL). METHOD: A systematic review of published literature and meeting abstracts was conducted to examine the efficacy of ZOL dosing strategies in clinical trials of osteoporosis, adjuvant therapy for breast cancer, and bone metastases from breast cancer. Bone resorption rates, tumor burden, skeletal health goals, and clinical data were considered when assessing ZOL in each setting. RESULTS: Dosing schedules vary between approved indications for osteoporosis and bone metastases and the investigational use in women receiving endocrine therapy for BC, taking into consideration the different levels of bone loss and tumor burden in each setting. Gradual bone loss in healthy postmenopausal women with osteopenia or osteoporosis can be prevented or treated with the approved biennial or annual ZOL (5 mg), respectively. Rapid bone loss in patients receiving adjuvant chemotherapy and/or endocrine therapy for early-stage BC and low tumor burden is managed in the clinical setting with ZOL 4 mg every 6 months. In patients with bone metastases, very high tumor burden, high bone resorption levels, and decreases in bone integrity are managed by the approved ZOL schedule (4 mg every 3-4 weeks) to prevent skeleton-related events. CONCLUSIONS: Dosing schedules are based on clinical evidence and vary depending on goals of therapy, rate of bone loss, and tumor burden. ZOL 5 mg every 12 months and every 24 months are approved for osteoporosis and osteopenia, respectively, whereas ZOL 4 mg every 6 months has been used during adjuvant endocrine therapy and ZOL 4 mg every 3-4 weeks is approved for managing bone metastases.

Bone demineralization in the lumbar spine of dogs submitted to prednisone therapy.

Glucocorticoids are drugs widely used in veterinary medicine; however, besides their clinical benefits, their use can trigger undesirable effects. A clinical trial was performed on eight healthy dogs with the intent of evaluating possible alterations in the bone mineral density after therapy with prednisone using a helical computed tomography. All animals received prednisone orally at a dose of 2 mg/kg of weight for 30 days. The bone mineral density was determined by obtaining the vertebral body radiodensity of the second lumbar vertebra values immediately before and after the administration of the medication. The experimental protocol allowed for the characterization of a significant (P < 0.01) reduction of the vertebral body radiodensity of the second lumbar vertebra. At the end of the experiment, it was characterized by a loss of bone mass of approximately 14%. None of the animals presented pathologic fracture at the end of the administration of the medication. This study verified that the alterations in the bone metabolism of the dogs submitted to the therapy with prednisone in a dosage of 2 mg/kg occur rapidly, which recommends a monitoring of the patients for the prevention of pathologic fractures.

Prolonged maternal magnesium administration and bone metabolism in neonates.

BACKGROUND: Magnesium sulfate (MgSO(4)) has been used as a tocolytic agent in cases of refractory preterm labor. Prolonged maternal administration of MgSO(4) may induce bone demineralization in the neonate. However, the effects of MgSO(4) on serum biochemistry related to bone metabolism in neonates remain unclear. AIM: To assess the effects of prolonged maternal administration of MgSO(4) on fetuses and neonates. STUDY DESIGN: This retrospective case-control study examined 167 neonates. Cases comprised 58 neonates whose mothers had received intravenous MgSO(4) administration for >5 days. Neonatal serum levels of magnesium (Mg), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were reviewed. We also investigated whether subject neonates showed appearance of osteopenia at the metaphyseal lines on radiography at birth. RESULTS: Mean serum Mg and P levels were significantly higher, and Ca levels were significantly lower, in cases than in controls at birth. Mean serum ALP level was 1188.5IU/l in cases, significantly higher than that in controls at birth. Bone abnormalities were noted on radiography in 2 subjects. By 3 weeks old, serum ALP levels did not differ significantly between cases and controls. Logistic regression analysis revealed maternal administration of MgSO(4) and multiple pregnancies were significantly related to serum ALP level in neonates at birth. CONCLUSION: Prolonged maternal administration of MgSO(4) significantly affects neonatal serum biochemistry related to bone metabolism. Potential long-term adverse effects on neonates and how Mg affects fetal bone metabolism in utero need to be investigated in future studies.

Bone mineral density in children with steroid-sensitive nephrotic syndrome.

OBJECTIVE: To observe the influence of prednisolone treatment on bone mineral density (BMD) in children with idiopathic nephrotic syndrome. METHODS: Duel-energy X-ray absorptiometry of lumbar spine (L1-L4) was performed on 40 patients (18 first episode and 22 relapsers) of steroid sensitive idiopathic nephrotic syndrome. RESULTS: Patients of first episode and relapsers had comparable values of mean age, weight, height, body mass index, serum calcium, phosphate, spine area, bone mineral content (BMC) and BMD. Relapsing nephrotic syndrome patients received significantly higher mean total cumulative dose of prednisolone in comparison to first episode (p<0.001). The BMD Z-scores were normal in 39 of 40 (97.5%) patients. On regression analysis, it was found that both BMC and BMD did not correlate with cumulative dose of prednisolone, when other co-variants such as age, weight, height and spine area were adjusted. CONCLUSION: Bone mineral density in steroid sensitive nephrotic syndrome is unaffected by cumulative dose of prednisolone therapy both in first episode as well as relapser group of patients.

Possible methods for the prevention of bone loss in persons with epilepsy.

Various antiepileptic drugs are known to cause bone mineral density (BMD) loss in persons with epilepsy. In general population studies, physical activity has a profound effect on bone health. Vitamin D deficiency, common in persons with epilepsy, is also associated with various chronic health conditions and osteoporosis in the general population. People with epilepsy would benefit from interventional research focused on the prevention of BMD loss. Exercise, healthy dietary habits and nutritional supplementation are important for the development and maintenance of bone health as well as for the prevention of comorbid conditions that are common in epilepsy. Consensus guidelines are needed for the prevention, screening and treatment of BMD loss in epilepsy.

Avaliação das metaloproteinases de matriz -2 e -9 em gatos com desmineralização óssea secundária à tirotoxicose induzida / Evaluation of matrix metalloproteinases -2 and -9 in cats under bone demineralization secondary to induced thyrotoxicosis

Observou-se significativo aumento de atividade das formas ativas das metaloproteinases -2 e -9 em gatos com tirotoxicose induzida e desmineralização óssea. As formas pró e intermediária da metaloproteinase -2 elevaram-se com 14 dias de administração hormonal, porém, posteriormente, houve uma tendência de queda. Observou-se correlação negativa entre a forma ativa das metaloproteinases de matriz -2 e -9 e a densidade mineral óssea da extremidade distal do rádio. Os resultados sugerem aumento da degradação da matriz colágena secundária com a elevação dos hormônios tiroidianos.

Significant increase of activity of active forms of matrix metalloproteinases -2 and -9 in cats under induced thyrotoxicosis and bone demineralization was observed. Pro and intermediated forms of matrix metalloproteinases -2 and -9 increased at 14 days of hormonal treatment, followed by decrease tendency. A negative correlation between active forms of matrix metalloproteinases -2 and -9 and bone mineral density of radius distal extremity was also observed. The results suggest an increase of collagen matrix degradation secondary to high levels of thyroid hormones.

Value of routine screening for bone demineralization in an urban population of patients with epilepsy.

BACKGROUND: Reduced bone mineral density (BMD) is increasingly recognized in patients receiving antiepileptic drug therapy. The precise prevalence is not known due to variability across populations studied. We set out to characterize the prevalence of abnormal BMD in an urban population of patients with epilepsy with the intent to determine the value of routine BMD screening. METHODS: We performed a cross-sectional study of 130 consecutive patients seen thorough our Comprehensive Epilepsy Center. BMD was measured using dual X-ray absorptiometry and was reported as T-score and Z-score. Additional information collected for each patient included age, race, gender, current and prior AEDs, ambulatory state, menopausal state, concomitant medications potentially associated with reduced bone mineralization, and comorbid illness potentially associated with reduced bone mineralization. Associations between reduced bone mineralization and variables were tested for significance using Fisher's exact test, Student's t-test, and Wilcoxon rank sum test. RESULTS: The average age of the entire study population was 43.5 (+/-12.5) years. Fifty-five percent of patients had T-score less than or equal to -1, the WHO criterion for osteopenia in postmenopausal women. The prevalence of Z-scores less than -2.0 was 15%, which is more than sixfold greater than expected. The markers for decreased BMD included older age or menopause in women, longer duration of therapy, and a history of use of phenytoin or phenobarbital. Assisted ambulation was also associated with low BMD. CONCLUSION: Our results indicate that reduced bone mineralization is prevalent and a significant health concern in an urban population of patients with epilepsy. Because of the high prevalence of reduced bone mineralization reported in numerous studies including this study, routinely screening for reduced bone mineralization is warranted in patients receiving anticonvulsant therapy.

Thyroid hormone-induced demineralisation of the vertebral skeleton of the eel, Anguilla anguilla.

The role of thyroid hormones (TH) in bone remodelling is controversial. Indeed, in humans, while they are necessary for normal growth and development, their overproduction can induce important mineral bone loss and osteoporosis. Intense bone resorption is a natural phenomenon also observed in some teleosts, during reproductive migration and fasting. Our work aimed at investigating the effects of chronic treatments with TH (thyroxin, T4 or triiodothyronine, T3) on bone resorption in a migratory fish, the European eel (Anguilla anguilla), a representative species of an ancient group of teleosts (Elopomorphs). The incineration method showed that TH induced a significant mineral loss in eel vertebral skeleton. Histology and histophysical (qualitative and quantitative microradiographs) methods were then applied to vertebral sections to determine which types of resorption were induced by TH. Quantitative image analysis of microradiographs showed that TH significantly increased the porosity of the vertebrae, demonstrating the induction of a severe bone loss. Histology revealed the appearance of large osteoclastic lacunae, indicating a stimulation of osteoclastic resorption. Quantitative image analysis of ultrathin microradiographs showed a significant increase of the size of osteocytic lacunae, indicating a stimulation of periosteocytic osteolysis. Finally, quantitative microradiographs indicated a significant fall of mineralisation degree. TH treatments did not stimulate the production of the calcium-bonded lipo-phospho-protein vitellogenin, indicating that TH-induced bone demineralisation was not mediated by any indirect effect on vitellogenesis. Our study demonstrates that TH may participate in the mobilisation of bone mineral stores in the eel, by inducing different types of vertebral bone resorption, such as osteoclastic resorption and periosteocytic osteolysis. These data suggest that the stimulatory action of TH on bone resorption may be an ancient regulatory mechanism in vertebrates.

Skeletal demineralization and fractures caused by fetal magnesium toxicity.

Two surviving female infants, born from a triplet pregnancy at 30 weeks gestation, were noted to have severe osteopenia and multiple fractures diagnosed at 20 days of age. Their mother had been treated for preterm labor with intravenous magnesium sulfate from week 22 until their birth at 30 weeks gestation. At birth, the triplets exhibited craniotabes with enlarged fontanelles and sutures. All developed Respiratory Distress Syndrome (RDS) and the two surviving infants required prolonged respiratory support. Serum calcium and phosphate levels were normal and alkaline phosphatase levels were increased. The infants were treated with supplements of calcium and phosphorous, with resultant healing of the multiple fractures without deformity. Fetal magnesium toxicity impairs bone mineralization and can lead to serious bone demineralization that may cause fractures in the newborn period that complicate recovery from respiratory disease. Early recognition and treatment may minimize complications related to osteopenia caused by fetal magnesium toxicity.

Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain.

This pilot study examined the effect of a low-dose E and pulsed progestogen hormone therapy (HT) regimen for add-back during long-term GnRH-agonist therapy on bone mineral density (BMD) in five patients with stage IV endometriosis. Bone mineral density was stable after initiation of HT for the entire follow-up period (up to 10 years). One patient stopped her treatment on two occasions to conceive and was successful each time with delivery of a normal baby. No patient had return of pelvic pain after HT add-back.