[New approaches to the role of estrogens in bone metabolism].
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Aged↗
Biomedical subjects
M Muñoz-Torres
Publications and source records attributed to M Muñoz-Torres.
Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group.
This randomized, double-masked, placebo-controlled trial evaluated the safety, tolerability and effects on bone mineral density (BMD) of alendronate in a large, multinational population of postmenopausal women with low bone mass. At 153 centers in 34 countries, 1908 otherwise healthy, postmenopausal women with lumbar spine BMD 2 standard deviations or more below the premenopausal adult mean were randomly assigned to receive oral alendronate 10 mg (n = 950) or placebo (n = 958) once daily for 1 year. All patients received 500 mg elemental calcium daily. Baseline characteristics of patients in the two treatment groups were similar. At 12 months, mean increases in BMD were significantly (p</=0.001) greater in the alendronate than the placebo group by 4.9% (95% confidence interval 4.6% to 5.2%) at the lumbar spine, 2.4% (2.0% to 2.8%) at the femoral neck, 3.6% (3.2% to 4.1%) at the trochanter and 3.0% (2.6% to 3.4%) for the total hip. The incidence of nonvertebral fractures was significantly lower in the alendronate than the placebo group (19 vs 37 patients with fractures), representing a 47% risk reduction for nonvertebral fracture for alendronate-treated patients (95% confidence interval 10% to 70%; p = 0.021). Incidences of adverse events, including upper gastrointestinal adverse events, were similar in the two groups. Therefore, for postmenopausal women with low bone mass, alendronate is well tolerated and produces significant, progressive increases in BMD at the lumbar spine and hip in addition to significant reduction in the risk of nonvertebral fracture.
Adult↗
Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis.
Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: -1.27 +/- 1.06, P < .001; FN: -0.48 +/- 0.96; P < .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively). Serum IGF-I was lower than in control subjects (P < .001), and significant differences were also found between patients with and without osteoporosis (P < .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis.
Adult↗
Methimazole-induced aplastic anemia in third exposure: successful treatment with recombinant human granulocyte colony-stimulating factor.
The major adverse reactions of antithyroid drugs are hematologic; aplastic anemia (AA) is one of the rarest and most severe complications. Use of recombinant human hemopoietic colony-stimulating factor was reported to be of benefit in patients who developed agranulocytosis, although there is still some doubt regarding the efficacy in AA. We present a case of a 58-year-old female patient with Graves' disease who developed AA in the third exposure to methimazole (MMI). The withdrawal of MMI and early treatment with 5 microg/kg per day recombinant human granulocyte colony-stimulating factor (G-CSF) for 9 days, allowed a favorable recovery of peripheral blood cell count. We conclude that the use of hemopoietic colony stimulating factors might be a suitable means to achieve the correction of severe thionamide-induced hematologic adverse reactions.
Anemia, Aplastic↗
[Intracranial hypertension in postoperative hypoparathyroidism].
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Female↗
Effect of tobacco consumption on bone mineral density in healthy young males.
Smoking is related to a decreased bone mass and increased risk of osteoporotic fractures. Nevertheless, the effect of smoking in males is poorly understood. The purpose of this study was to assess the repercussion of smoking on bone mass in otherwise healthy male smokers and its relationship with markers of mineral metabolism and hormone profile. We measured bone mineral density (BMD) in 57 healthy males (26 nonsmokers, 31 smokers; aged 20-45 years) by dual X-ray absorptiometry (DXA, Hologic QDR1000) in the lumbar spine and proximal femur. In a subset we measured biochemical markers of bone metabolism and hormonal profile. We found significant differences in BMD between heavy smokers (more than 20 cigarettes/day) and nonsmokers in all skeletal sites. Serum levels of dehydroepiandrosterone sulfate (S-DHEAS) were lower in smokers and correlated with femoral BMD measurements. No significant differences in bone turnover markers were found. Our findings show that smoking by healthy young males is associated with decreased bone mass.
Absorptiometry, Photon↗
Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover.
Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.
Absorptiometry, Photon↗
Virilizing mature ovarian cystic teratomas.
Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown factor related to diabetes mellitus is the origin of the virilization.
Aged↗
Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause.
OBJECTIVE: The effect of hyperthyroidism on osteoporosis risk and its reversal after control of hyperthyroidism remains somewhat controversial. We assessed the values of bone mineral density in hyperthyroid patients and in former hyperthyroid patients euthyroid on medical therapy, as well as the influence of aetiology and menopause upon bone mass. DESIGN: The values of bone mineral density in hyperthyroid patients (active) and former hyperthyroid patients euthyroid on medical therapy (controlled), were compared, together with data from our control group and from the Spanish reference population. We also compared the values of bone mineral density in patients with Graves' disease with those in patients with toxic nodular goitre and assessed the influence of the menopause. PATIENTS: We studied 127 consecutive hyperthyroid patients (age 41 +/- 16 years; 110 females, 17 males; 102 Graves' disease and 25 toxic nodular goitre); 78 were active (group A) and 49 controlled on medical therapy (carbimazole, mean time of euthyroidism 7.5 +/- 9.1 months; group B). We also studied 43 healthy subjects (age 40 +/- 14 years; 41 females, two males; group C). MEASUREMENTS: Bone mineral density was assessed by dual X-ray absorptiometry at lumbar spine (L2-L4), femoral neck and Ward's triangle. Data were expressed as g/cm2 and as a Z score (SD vs Spanish reference population adjusted by age and sex). Blood was obtained to measure the levels of free T4, TSH and TSH receptor antibody. RESULTS: Patients with active hyperthyroidism showed a generalized reduction in axial bone mineral density in comparison with both the control group and the reference population, whereas former hyperthyroid patients showed partial recovery of bone mass in lumbar spine and Ward's triangle. Mean Z scores at lumbar spine, femoral neck and Ward's triangle were: -0.92, -0.79 and -0.89 in group A; -0.74, -0.23 and -0.44 in group B and 0.18, 0.09 and 0.36 in group C, respectively. No differences were found between bone mineral density values from patients with Graves' disease and those with toxic nodular goitre, nor between pre and postmenopausal hyperthyroid women once adjusted by age and sex. CONCLUSIONS: Our data suggest that hyperthyroid patients show a generalized reduction of bone mass in the axial skeleton and that only partial recovery is present in former hyperthyroid patients after a mean of 7.5 months of biochemical euthyroidism. This recovery is insufficient to normalize the bone density in lumbar spine and Ward's triangle, although femoral bone mass was not different from that of the control group. The extent and degree of hyperthyroid bone disease surpass the effects of the menopause on the bone mass. The aetiology of hyperthyroidism does not seem to play any role in the severity of hyperthyroid bone disease.
Absorptiometry, Photon↗
Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and mineral metabolism.
The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward's triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P < 0.05), with a 5-10% net gain during follow-up. Nevertheless, final bone mass was 4-8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6-9 months; resorption bone markers showed a significant reduction at the 3 month evaluation. These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6-9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.
Absorptiometry, Photon↗
Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus.
Previous studies suggest that low bone mass is a potential complication of insulin-dependent diabetes mellitus. Nevertheless, the factors that influence diabetic osteopenia are not well established. In order to evaluate the prevalence and magnitude of diabetic osteopenia and its association with clinical and metabolic variables, we studied 94 consecutive patients with insulin-dependent diabetes mellitus. Their age ranged from 20 to 56 years and duration of diabetes varied from 1 to 35 years. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and proximal femur and the values were expressed as z-score. The presence and extent of microvascular complications, degree of metabolic control, and other risk factors for osteoporosis were recorded and some biochemical markers of bone metabolism were assessed. Diabetic patients showed reduced BMD in all sites (lumbar spine: -0.89 +/- 1.21; femoral neck: -0.99 +/- 1.24; Ward triangle: -1.05 +/- 1.24; P < 0.0001). Of the 94 patients 19.1% met diagnostic criteria for osteoporosis. BMD correlated with body mass index in all sites and with the duration of disease in Ward's triangle. Presence and extent of diabetic complications were associated with lower BMD, as was smoking. No correlation was found between BMD and biochemical markers. In conclusion, osteopenia is a common complication in patients with insulin-dependent diabetes mellitus. Microvascular complications are a critical point in the progression of diabetic osteopenia. Other risk factors for osteoporosis (nutritional status and smoking) must be taken into account.
Absorptiometry, Photon↗
[Elevation of muscular enzymes and idiopathic hypoparathyroidism].
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Adult↗
Bone mass in androgen-insensitivity syndrome: response to hormonal replacement therapy.
The response of bone mass to long-term treatment with estrogen and progesterone in patients with complete androgen-insensitivity syndrome (AIS) is unknown. We report a 17-year-old female patient (karyotype 46 X, Y) with AIS studied during a 4-year period. Bone mineral density (BMD) measured by dual X-ray absorptiometry in lumbar spine and proximal femur was sharply reduced at the initial visit; and remained unchanged during long-term follow-up on hormone replacement therapy with estrogens and progestin. Bone metabolism markers were all in the normal range. The lack of significant increase in BMD highlights the importance of androgens on bone physiology that cannot be balanced in spite of an appropriate estrogenic milieu.
Absorptiometry, Photon↗
Hyperinsulinemia in polycystic ovary syndrome: relationship to clinical and hormonal factors.
We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19-30 years. None of the patients or control women had a body mass index above 27 kg/m2. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.
Adolescent↗
Bone mineral density, sex steroids, and mineral metabolism in premenopausal smokers.
Smoking is related to decreased bone mass and increased risk of osteoporotic fractures. However, the harmful effects of smoking on bone have not been well characterized. The purpose of this study was to assess the repercussions of smoking on bone mass in premenopausal women, and the relationship between these effects and parameters of mineral metabolism and hormone profile. We measured bone mineral density (BMD) in 101 premenopausal women (47 smokers, 54 nonsmokers) with dual-energy X-ray absorptiometry (DeXA) of the proximal femur and lumbar spine. In a subgroup of the sample (16 smokers, 15 nonsmokers) we measured biochemical indicators of mineral metabolism and hormone profile. BMD in the femoral neck, Ward's triangle, and the intertrochanter region was significantly lower in smokers (P < 0.05) than in nonsmokers. Concentrations of sex hormone-binding globulin were higher, and free testosterone index (FTI) was lower (P < 0.05) in smokers. We found no significant differences between the groups in parameters of mineral metabolism. Concentrations of dehydroepiandrosterone sulfate and free testosterone index were directly correlated with values of BMD in different sites. Our findings show that smoking by premenopausal women is associated with decreased BMD and characteristic changes in the hormone profile.
Absorptiometry, Photon↗
Reduction of endogenous, ovarian and adrenal androgens with ketoconazole does not alter insulin response in the polycystic ovary syndrome.
Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally (400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate, and free testosterone index) decreased (p < 0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p < 0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome.
Adolescent↗
Bone mineral density is decreased in hyperthyroidism.
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Bone Density↗
Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism.
The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testesterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effect also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 +/- 4.6 vs 12.4 +/- 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%).(ABSTRACT TRUNCATED AT 250 WORDS)
Acne Vulgaris↗