RESUMEN
UNLABELLED: Young adults with cystic fibrosis have compromised plate-like trabecular microstructure, altered axial alignment of trabeculae, and reduced connectivity between trabeculae that may contribute to the reduced bone strength and increased fracture risk observed in this patient population. INTRODUCTION: The risk of fracture is increased in patients with cystic fibrosis (CF). Individual trabecular segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography (HR-pQCT) images segments trabecular bone into individual plates and rods of different alignment and connectivity, which are important determinants of trabecular bone strength. We sought to determine whether alterations in ITS variables are present in patients with CF and may help explain their increased fracture risk. METHODS: Thirty patients with CF ages 18-40 years underwent DXA scans of the hip and spine and HR-pQCT scans of the radius and tibia with further assessment of trabecular microstructure by ITS. These CF patients were compared with 60 healthy controls matched for age (±2 years), race, and gender. RESULTS: Plate volume fraction, thickness, and density as well as plate-plate and plate-rod connectivity were reduced, and axial alignment of trabeculae was lower in subjects with CF at both the radius and the tibia (p < 0.05 for all). At the radius, adjustment for BMI eliminated most of these differences. At the tibia, however, reductions in plate volume fraction and number, axially aligned trabeculae, and plate-plate connectivity remained significant after adjustment for BMI alone and for BMI and aBMD (p < 0.05 for all). CONCLUSIONS: Young adults with CF have compromised plate-like and axially aligned trabecular morphology and reduced connectivity between trabeculae. ITS analysis provides unique information about bone integrity, and these trabecular deficits may help explain the increased fracture risk in adults with CF not accounted for by BMD and/or traditional bone microarchitecture measurements.
Asunto(s)
Densidad Ósea , Fibrosis Quística/fisiopatología , Radio (Anatomía)/patología , Tibia/patología , Absorciometría de Fotón , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
SUMMARY: We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers. INTRODUCTION: Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. METHODS: We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers. RESULTS: Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (-0.28% vs -0.88%; p = 0.008) and the spine (-0.74% vs -1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (-0.35% vs -0.60%; p = 0.08) and a similar trend at the FN (-0.39% vs -0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (-0.48% vs -0.82%; p = 0.02), but not at the spine (-0.40% vs -0.56%; p = 0.23). CONCLUSIONS: Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.
Asunto(s)
Antihipertensivos/farmacología , Densidad Ósea/efectos de los fármacos , Osteoporosis/prevención & control , Antagonistas Adrenérgicos beta/farmacología , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Estudios de Cohortes , Femenino , Cuello Femoral/efectos de los fármacos , Cuello Femoral/fisiopatología , Humanos , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis/fisiopatología , Puntaje de Propensión , Factores de Riesgo , Factores Socioeconómicos , Inhibidores de los Simportadores del Cloruro de Sodio/farmacologíaRESUMEN
SUMMARY: Patients with type 2 diabetes mellitus (DM2) have increased fracture risk. We found that African-American women with DM2 have increased cortical porosity and lower cortical bone density at the radius than non-diabetic controls. These cortical deficits are associated with hyperglycemia and may contribute to skeletal fragility associated with DM2. INTRODUCTION: Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. METHODS: We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. RESULTS: Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=-0.54, p=0.018). CONCLUSIONS: DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further, our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2.
Asunto(s)
Diabetes Mellitus Tipo 2/patología , Radio (Anatomía)/patología , Absorciometría de Fotón/métodos , Negro o Afroamericano/estadística & datos numéricos , Glucemia/metabolismo , Densidad Ósea/fisiología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/fisiopatología , Ayuno/sangre , Femenino , Articulación de la Cadera/fisiopatología , Humanos , Resistencia a la Insulina/fisiología , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Porosidad , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/fisiopatología , Tibia/diagnóstico por imagen , Tibia/patología , Tibia/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: Osteoporosis represents a growing public health concern; however, current rates of management are sub-optimal. The aim of our study was to assess, in a randomized controlled trial, the effect of a mailed educational intervention on older adults' knowledge, attitudes, and preventive behaviors regarding osteoporosis. The setting was a large publicly funded state pharmacy benefits program. The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people. METHODS: All women aged over 65 years, and all men and women with a history of fracture or long-term oral use of glucocorticoid, were included. Approximately half of the participants (intervention group) were randomly selected to receive three mailings aimed at improving knowledge of osteoporosis and enhancing preventive activities, such as using calcium and vitamin D, reducing fall risks in the home, obtaining a bone mineral density (BMD) test, and taking medications when necessary. The other participants did not receive the intervention mailings and served as controls. We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge, attitudes, self-efficacy (confidence in one's ability to perform specific activities), and behavior regarding osteoporosis prevention and treatment. Six hundred randomly selected participants in the intervention group and an equal number in the control group were invited to participate. RESULTS: Twenty-six had died and 636 of the remaining 1,185 (54%) completed the survey. Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors. All scales had good reliability (all Cronbach's alphas>0.65). Knowledge of osteoporosis was generally very good and did not differ between intervention (mean=65% correct responses) and control subjects (mean=67% correct; P=0.4). Perceived susceptibility to osteoporosis was relatively high and similar across groups (P=0.4). Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention (mean=4.3 on a 0-5 scale) and control (mean=4.2, P=0.03) groups . On average, subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group (P=0.5). CONCLUSIONS: Compared with the controls, a mailed educational intervention for osteoporosis was not associated with better knowledge, higher perceived susceptibility, or performance of preventive measures among the at-risk older adults that we studied. The intervention group demonstrated a small increase in self-efficacy. More intensive patient interventions or intervention aimed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures.
Asunto(s)
Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Osteoporosis/terapia , Educación del Paciente como Asunto , Anciano , Femenino , Humanos , Masculino , Pennsylvania , AutoeficaciaRESUMEN
The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.
Asunto(s)
Anabolizantes/uso terapéutico , Hormona Paratiroidea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Desarrollo Óseo/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Femenino , Humanos , Masculino , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológicoRESUMEN
We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42-52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E(2)), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations ( beta=0.003, partial r2=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations ( beta=-0.216, partial r2=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period.
Asunto(s)
Colágeno Tipo I/orina , Menopausia/sangre , Menopausia/orina , Osteocalcina/sangre , Péptidos/orina , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Resorción Ósea/fisiopatología , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Osteogénesis/fisiología , Perimenopausia/metabolismo , Premenopausia/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Tirotropina/sangreRESUMEN
Large population-based surveys have shown that approximately 30% of people over age 65 years have osteoporosis and that 17% of the population over 65 years will sustain a fracture during their lifetime. Many people with osteoporosis are never being evaluated even though effective treatments are available. We examined why primary care physicians order few bone mineral density scans. We conducted a cross-sectional survey of primary care physicians practicing in any of the six New England states. Target physician specialties included internal medicine, general practitioners/family physicians, and obstetrician-gynecologists who had a facsimile number listed with the American Medical Association. Demographics, practice characteristics, use of bone densitometry, and attitudes regarding osteoporosis, bone densitometry and health maintenance were assessed by questionnaire. Twelve percent (n=494) of the physicians responded to the questionnaire. Respondents were similar to non-respondents with respect to years of practice, training and geographical state, though they were more likely to be female (p < or =0.05). Respondents had a mean age of 51 years, and 51% were trained in internal medicine, 25% in general practice/family practice and 24% in obstetrics-gynecology. The mean number of self-reported bone densitometry referrals per month was 10+/-11, and 25% of respondents reported that they referred fewer than 4 patients per month. In adjusted logistic models, factors significantly associated with referring fewer than 4 patients per month were: training in internal medicine (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9) or general practice/family practice (OR 2.6, 95% CI 1.3-5.2) versus obstetrics-gynecology; practicing in an urban setting (OR 2.5, 95% CI 1.3-4.9) or rural/small town setting (OR 2.2, 95% CI 1.2-4.1) versus a suburban setting; spending less than 50% of professional time in patient care (OR 4.0, 95% CI 1.7-9.5); seeing the lowest proportion of postmenopausal women (OR 2.5., 95% CI 1.2-5.3); the belief that calcium and vitamin D are adequate to treat osteoporosis (OR 2.1, 95% CI 1.0-4.5); and the belief that osteoporosis treatment should not be based on bone density results (OR 3.2, 95% CI 1.7-6.1). Potentially modifiable physician beliefs and a number of practice characteristics are associated with low referral rates for bone densitometry. Educational strategies aimed at improving the use of bone density testing should consider these factors.
Asunto(s)
Absorciometría de Fotón/estadística & datos numéricos , Densidad Ósea/fisiología , Pautas de la Práctica en Medicina , Estudios Transversales , Medicina Familiar y Comunitaria , Humanos , Persona de Mediana Edad , New England , Oportunidad Relativa , Osteoporosis/diagnóstico , Atención Primaria de Salud , Derivación y Consulta/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42-52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -10 for lumbar spine [95% confidence interval (CI): -0.13, -0.06] and r = -0.08 for femoral neck (95% CI: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period.
Asunto(s)
Densidad Ósea/fisiología , Climaterio/sangre , Hormona Folículo Estimulante/sangre , Hormonas Esteroides Gonadales/sangre , Osteoporosis Posmenopáusica/sangre , Adulto , Climaterio/etnología , Climaterio/fisiología , Estradiol/sangre , Femenino , Cuello Femoral/fisiología , Humanos , Estudios Longitudinales , Vértebras Lumbares/fisiología , Ciclo Menstrual/sangre , Persona de Mediana Edad , Osteoporosis Posmenopáusica/etnología , Osteoporosis Posmenopáusica/fisiopatología , Premenopausia/sangre , Premenopausia/etnología , Premenopausia/fisiología , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangreRESUMEN
BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.
Asunto(s)
Antineoplásicos Hormonales/efectos adversos , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Hormona Liberadora de Gonadotropina/agonistas , Leuprolida/efectos adversos , Osteoporosis/prevención & control , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antineoplásicos Hormonales/uso terapéutico , Resorción Ósea/inducido químicamente , Resorción Ósea/prevención & control , Difosfonatos/efectos adversos , Difosfonatos/farmacología , Fémur/efectos de los fármacos , Humanos , Leuprolida/uso terapéutico , Vértebras Lumbares/efectos de los fármacos , Masculino , Osteocalcina/sangre , Osteoporosis/inducido químicamente , Pamidronato , Huesos Pélvicos/efectos de los fármacos , Neoplasias de la Próstata/fisiopatologíaRESUMEN
Androstenedione is a steroid hormone and the major precursor to testosterone. It is available without prescription and taken with the expectation that it will be converted to testosterone endogenously and increase strength and athletic performance. The metabolism of orally administered testosterone has not been well studied. We randomly assigned 37 healthy men to receive 0, 100, or 300 mg oral androstenedione in a single daily dose for 7 d. Single 8-h urine collections were performed on the day before the start of the androstenedione administration and on d 1 and 7 to assess excretion rates of free and glucuronide- conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone. Serum testosterone glucuronide concentrations were measured by frequent blood sampling over 8 h on d 1 in 16 subjects (5 each in the 0 and 100 mg group and 6 in the 300 mg group). In the control group, mean (+/-SE) d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 3 +/- 1, 215 +/- 26, 175 +/- 26, and 0.4 +/- 0.1 microg/h, respectively. In the 100 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 47 +/- 11, 3,836 +/- 458, 4,306 +/- 458, and 1.6 +/- 0.2 microg/h, respectively. In the 300 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 115 +/- 39, 8,142 +/- 1,362, 10,070 +/- 1,999, and 7.7 +/- 1.5 microg/h, respectively. Urinary excretion rates of all metabolites were greater in both the 100 and 300 mg groups than in controls (P < 0.0001). Urinary excretion rates of testosterone (P = 0.007), androsterone (P = 0.009), etiocholanolone (P = 0.0005), and dihydrotestosterone (P < 0.0001) were greater in the subjects who received 300 mg androstenedione than in those who received 100 mg. In the treated groups, excretion of free testosterone accounted for less than 0.1% of the total excreted testosterone measured. Serum testosterone glucuronide levels increased significantly during frequent blood sampling in both the 100 and 300 mg groups compared with controls (P = 0.0005 for the 100 mg group; P < 0.0001 for the 300 mg group). The net mean changes in area under the curve for serum testosterone glucuronide were -18 +/- 25%, 579 +/- 572%, and 1267 +/- 1675% in the groups receiving 0, 100, and 300 mg/d androstenedione, respectively. We conclude that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than the changes observed in serum total testosterone concentrations. These findings demonstrate that orally administered androstenedione is largely metabolized to testosterone glucuronide and other androgen metabolites before release into the general circulation.
Asunto(s)
Androstenodiona/metabolismo , Administración Oral , Adulto , Androstenodiona/sangre , Androstenodiona/orina , Androsterona/orina , Pueblo Asiatico , Población Negra , Dihidrotestosterona/orina , Etiocolanolona/orina , Glucurónidos/sangre , Glucurónidos/orina , Humanos , Masculino , Testosterona/sangre , Testosterona/orina , Estados Unidos , Población BlancaRESUMEN
BACKGROUND: The objective of this study was to determine the prevalence of low bone mineral density in men with prostate carcinoma and no history of androgen-deprivation therapy. METHODS: The authors conducted a cross-sectional study in 41 hormone-naïve men with locally advanced, lymph node positive, or recurrent prostate carcinoma and no radiographic evidence of bone metastases. Bone mineral density of the total hip, posterior-anterior (PA) lumbar spine, and lateral lumbar spine was determined by dual-energy X-ray absorptiometry (DXA) using a densitometer. Trabecular bone mineral density of the lumbar spine was determined by quantitative computed tomography (QCT). Bone mineral density results were expressed in standard deviation units relative to young adult men (T score) and relative to age-matched men (Z score). RESULTS: Fourteen of 41 men (34%; 95% confidence interval [95% CI], 20-51%) had T scores < -1.0 at one or more skeletal sites by DXA, 12 of 41 men (29%; 95% CI, 16-42%) had T scores between -1.0 and -2.5, and 2 of 41 men (5%; 95% CI, 1-17%) had T scores < -2.5. Thirty-nine of 41 men (95%; 95% CI, 83-99%) had T scores < -1.0 by QCT, 13 of 41 men (31%; 95% CI 18-48%) had T scores between -1.0 and -2.5, and 26 of 41 men (63%; 95% CI, 47-78%) had T scores < -2.5. T scores for trabecular bone mineral density of the lumbar spine were significantly lower than T scores for either the total hip (P < 0.001) or the PA lumbar spine (P < 0.001). The mean Z score for trabecular bone mineral density of the lumbar spine was -0.7 +/- 0.9. Hypogonadism, hypovitaminosis D, and dietary calcium intakes below the Recommended Daily Allowance were observed in 20%, and 17%, and 59% of study participants, respectively. CONCLUSIONS: Many hormone-naïve men with prostate carcinoma have low bone mineral density. QCT is a more sensitive method than DXA for diagnosing low bone mineral density in this patient population. Trabecular bone mineral density is lower than expected for age and risk factors for osteoporosis are common.
Asunto(s)
Densidad Ósea , Neoplasias de la Próstata/metabolismo , Factores de Edad , Anciano , Calcio de la Dieta/administración & dosificación , Estudios Transversales , Humanos , Hipogonadismo/complicaciones , Masculino , Tomografía Computarizada por Rayos X , Deficiencia de Vitamina D/complicacionesRESUMEN
Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/etiología , Síndrome de Emaciación por VIH/metabolismo , Hipogonadismo/metabolismo , Testosterona/uso terapéutico , Humanos , Masculino , Inhibidores de Proteasas/farmacologíaRESUMEN
Hypogonadism is associated with osteoporosis in men. GnRH- agonist-induced hypogonadism increases bone turnover and bone loss in men, but the mechanism underlying these changes is unknown. To determine whether gonadal steroid deprivation increases the skeletal sensitivity to PTH or blunts the ability of PTH to promote 1,25-dihydroxyvitamin D formation, we infused human PTH-(1-34) at a dose of 0.55 U/kg.h for 24 h, in 11 men (ages, 50-82 yr) with locally advanced, node-positive, or biochemically recurrent prostate cancer but no evidence of bone metastases. PTH infusions were performed before initiation of GnRH agonist therapy (leuprolide acetate, 22.5 mg im, every 3 months) and again after 6 months of confirmed GnRH agonist-induced hypogonadism. Serum osteocalcin (OC), bone- specific alkaline phosphatase (BSAP), N-telopeptide (NTX), whole-blood ionized calcium, and 1,25-dihydroxyvitamin D were measured at baseline and every 6 h during each PTH infusion. Urinary NTX and free deoxypyridinoline (DPD) were assessed on spot morning samples before PTH infusion and on 24-h samples collected during the PTH infusions. Sex steroid levels were lowered to the castrate range in all subjects. Baseline serum NTX levels (drawn before PTH infusion) increased from 9.1 +/- 3.7 before leuprolide therapy to 13.9 +/- 5.0 nmol bone collagen equivalents (BCE)/L after leuprolide therapy (P = 0.003). Spot urine NTX collected before PTH infusion increased from 28 +/- 8 before leuprolide therapy to 49 +/- 17 nmol BCE/mmol creatinine after leuprolide therapy (P < 0.001), and urinary DPD increased from 4.7 +/- 1.1 to 7.4 +/- 1.8 nmol BCE/mmol creatinine (P < 0.001). Baseline serum OC and BSAP levels drawn before each PTH infusion did not change before vs. after leuprolide therapy. Serum NTX levels increased significantly during PTH infusion pre-GnRH agonist therapy (P < 0.001), and the rate of increase was greater after 6 months of GnRH agonist-induced hypogonadism (P < 0.01 for the difference in rates of change before and after GnRH agonist administration). Serum OC and BSAP levels decreased during PTH infusion (P < 0.001 for OC and P = 0.002 for BSAP), but the rates of decrease did not differ before or after leuprolide therapy (P = 0.45 for OC and P: = 0.19 for BSAP). Whole-blood ionized calcium levels increased during PTH infusion (P < 0.001), and the rate of increase was greater after GnRH agonist-induced hypogonadism (P = 0.068). Serum 1,25-dihydroxyvitamin D levels increased in response to PTH infusion before leuprolide therapy (P = 0.022), but there was no difference in the rate of increase before or after leuprolide therapy (P = 0.66). The incremental increase in urinary NTX excretion, but not DPD, during PTH infusion was greater after 6 months of leuprolide therapy (P = 0.029 for NTX, P = 0.578 for DPD). We conclude that suppression of sex steroids in elderly men increases the skeletal responsiveness to the bone resorbing effects of PTH infusion but does not affect the response of bone formation markers or 1,25-dihydroxyvitamin D to PTH. Changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.
Asunto(s)
Huesos/fisiopatología , Leuprolida/uso terapéutico , Neoplasias de la Próstata/fisiopatología , Teriparatido , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Aminoácidos/orina , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores/sangre , Biomarcadores/orina , Huesos/efectos de los fármacos , Calcitriol/sangre , Calcio/sangre , Colágeno/sangre , Colágeno/orina , Colágeno Tipo I , Difosfonatos/uso terapéutico , Humanos , Hipogonadismo/sangre , Hipogonadismo/inducido químicamente , Leuprolida/efectos adversos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/fisiopatología , Osteocalcina/sangre , Pamidronato , Péptidos/sangre , Péptidos/orina , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Factores de TiempoRESUMEN
CONTEXT: Several anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports have suggested that use of these supplements can cause positive urine test results for metabolites of the prohibited steroid nandrolone. OBJECTIVES: To assess the content and purity of OTC androstenedione and to determine if androstenedione and 19-norandrostenedione administration causes positive urine test results for 19-norandrosterone, a nandrolone metabolite. DESIGN: Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000. SETTING: Outpatient facility of a university hospital. PARTICIPANTS: A total of 41 healthy men aged 20 to 44 years. INTERVENTION: Participants were randomly assigned to receive oral androstenedione, 100 mg/d (n = 13) or 300 mg/d (n = 11) for 7 days, or no androstenedione (n = 13); in addition, 4 patients received 10 microg of 19-norandrostenedione. MAIN OUTCOME MEASURES: Content of OTC androstenedione preparations; level of 19-norandrosterone in urine samples, determined by mass spectrometry, compared among the 3 randomized groups at day 1 and day 7, and among the participants who received 19-norandrostenedione from October 1998 to April 2000. RESULTS: All urine samples from participants treated with androstenedione contained 19-norandrosterone, while no samples from the no-androstenedione group did. Urinary concentrations were averaged for day 1 vs day 7 measurements; mean (SD) 19-norandrosterone concentrations in the 100-mg/d and 300-mg/d groups were 3.8 (2.5) ng/mL and 10.2 (6.9) ng/mL, respectively (P =. 006). The 19-norandrosterone content exceeded the cutoff for reporting positive cases (>2.0 ng/mL) in 20 of 24. The androstenedione preparation used was pure at a sensitivity of 0.1%, but at 0.001% 19-norandrostenedione was found. For the 4 participants to whom 10 microg of 19-norandrostenedione was administered, 19-norandrosterone was found in all urine samples. Of 7 brands of androstenedione analyzed at the 1% level, 1 contained no androstenedione, 1 contained 10 mg of testosterone, and 4 more contained 90% or less of the amount stated on the label. CONCLUSION: Our study suggests that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause urine test results positive for 19-norandrosterone, the standard marker for nandrolone use. Oral steroid doses as small as 10 microg are absorbed and excreted in urine. Some brands of androstenedione are grossly mislabeled. Careful analysis of androstenedione preparations is recommended in all studies of its biological effects. JAMA. 2000;284:2618-2621.
Asunto(s)
Anabolizantes/metabolismo , Androstenodiona/análogos & derivados , Androstenodiona/metabolismo , Contaminación de Medicamentos , Estranos/orina , Nandrolona/metabolismo , Medicamentos sin Prescripción , Adulto , Androstenodiona/química , Androstenodiona/farmacología , Suplementos Dietéticos , Humanos , Masculino , Espectrometría de Masas , Detección de Abuso de Sustancias , Estados Unidos , UrinálisisRESUMEN
Lateral spine dual-energy x-ray absorptiometry (DXA) selectively measures the trabecular-rich vertebral bodies without the contributions of the cortical-rich posterior elements of the spine and is less affected by spinal degenerative disease than posterior-anterior DXA. We tested whether lateral DXA detects vertebral osteoporosis more often and is more sensitive to age-related bone loss than posterior-anterior DXA in 193 healthy, community-dwelling men aged 51-81 years (mean +/- SD; 67 +/- 8 years). All men had supine lateral, posterior-anterior, and proximal femur DXA scans on a Hologic QDR 2000 densitometer. A subset (n = 102) had repeat scans after 4 years to determine annualized rates of change in bone mineral density (BMD). Age was inversely and significantly associated with BMD in the midlateral (r = -0.27) and lateral (r = -0.24) but not posterior-anterior (r = 0.04) projections. Midlateral (-1.43 +/- 3.48% per year; p = 0.0001), lateral (-0.27 +/- 1.68% per year; p = 0.12), and hip (-0.19 +/- 1.02% per year; p = 0.06) BMD decreased, whereas posterior-anterior BMD increased (0.73 +/- 1.11% per year; p = 0.0001) during follow-up. When compared with normal values in 43 men aged 21-42 years, mean T scores were significantly lower with lateral (-1.47 +/- 1.32) and midlateral (-1.57 +/- 1.36) than posterior-anterior (-0.12 +/- 1.30; p < 0.0001) DXA. Only 2.6% of the older men were considered osteoporotic (T score < or = -2.5) at the posterior-anterior spine, whereas 11.0% were osteoporotic at the femoral neck, 22.5% at the lateral spine, and 24.6% were osteoporotic at the midlateral spine. We conclude that supine lateral DXA identifies considerably more men as osteoporotic and is more sensitive to age-related bone loss than posterior-anterior DXA. Spinal osteoporosis may represent a substantially greater health problem among older men than previously recognized.
Asunto(s)
Absorciometría de Fotón/métodos , Densidad Ósea , Osteoporosis/diagnóstico , Adulto , Factores de Edad , Anciano , Envejecimiento , Fémur , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Columna VertebralRESUMEN
CONTEXT: Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. OBJECTIVE: To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. DESIGN: Open-label randomized controlled trial conducted between October 1998 and April 1999. SETTING: General clinical research center of a tertiary-care, university-affiliated hospital. PARTICIPANTS: Forty-two healthy men aged 20 to 40 years. INTERVENTION: Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. MAIN OUTCOME MEASURES: Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. RESULTS: Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. CONCLUSIONS: Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.
Asunto(s)
Androstenodiona/farmacología , Testosterona/sangre , Administración Oral , Adulto , Androstenodiona/administración & dosificación , Androstenodiona/sangre , Área Bajo la Curva , Estradiol/sangre , Estrona/sangre , Humanos , Masculino , Testosterona/metabolismoAsunto(s)
Absorciometría de Fotón , Densidad Ósea , Pubertad Tardía/fisiopatología , Adulto , Humanos , MasculinoRESUMEN
Although a causal association between estrogen deficiency and bone loss has been established for many years, the mechanism by which estrogen deficiency leads to bone loss is unclear. Estrogen deficiency could induce bone loss either by a direct effect on bone cells to modify the production of bone-resorbing cytokines or by altering the production or response to calcium regulatory hormones such as PTH and 1,25-dihydroxyvitamin D. To assess the effects of ovarian hormones on calcium regulatory hormones, we evaluated the ability of calcium to suppress PTH secretion and the ability of PTH to increase serum 1,25-dihydroxyvitamin D and whole blood ionic calcium levels in women before and after GnRH analog-induced ovarian suppression. Sixteen women with endometriosis underwent i.v. infusion of calcium (1.1 mg calcium gluconate/cc in 5% dextrose) at a rate of 4 cc/kg x h (n = 7) or human PTH-(1-34) (Parathar) at a dose of 0.55 U/kg x h (n = 9) before and after 6 months of suppression of ovarian function with the GnRH analog nafarelin acetate (200 microg, intranasally, twice daily). Initial infusions were performed between days 6-10 of the menstrual cycle. Serum PTH and whole blood ionic calcium levels were measured at -20, -10, and 0 min and then every 10 min for 2 h during i.v. calcium infusions. Whole blood ionic calcium and 1,25-dihydroxyvitamin D levels were measured every 6 h for 24 h during i.v. human PTH-(1-34) infusions. Serum estradiol levels were markedly suppressed by nafarelin therapy in both groups of women. The relationship between whole blood ionic calcium and serum PTH levels was similar before and during nafarelin-induced ovarian suppression. The net change and rate of rise in serum 1,25-dihydroxyvitamin D levels in response to PTH infusion were similar before and during nafarelin therapy. Peak whole blood ionic calcium and incremental increases in ionic calcium in response to PTH were similar before and during nafarelin therapy. Our data suggest that ovarian suppression does not alter the regulation of PTH secretion in response to calcium, the ability of PTH to stimulate 1,25-dihydroxyvitamin D formation, or the skeletal sensitivity to PTH. These findings suggest that alterations in calcium regulatory hormones by estrogen deficiency are unlikely to play a major role in the pathogenesis of estrogen deficiency bone loss.
Asunto(s)
Ovario/efectos de los fármacos , Hormona Paratiroidea/metabolismo , Teriparatido/farmacología , Vitamina D/análogos & derivados , Adulto , Calcio/sangre , Gluconato de Calcio/farmacología , Estradiol/sangre , Femenino , Hormonas/farmacología , Humanos , Nafarelina/farmacología , Ovario/metabolismo , Fosfatos/sangre , Vitamina D/metabolismoRESUMEN
Intermittent PTH administration increases spinal bone mineral density (BMD) and prevents bone loss from the hip and total body in young women treated with a long acting GnRH analog for endometriosis. To establish whether these beneficial effects on BMD persist after PTH administration is discontinued, we remeasured BMD and biochemical markers of bone turnover in 38 women with endometriosis who had been treated with a GnRH analog alone (nafarelin acetate; 200 microg, intranasally, twice daily; n = 23; group 1) or who had received nafarelin plus human PTH-(1-34) (40 microg/day, s.c.; n = 15; group 2) for 6-12 months 1 yr after therapy was completed. Cyclic menstrual function returned promptly after nafarelin therapy was discontinued. In group 1, BMD increased significantly at all sites [P < 0.001 for the anterior-posterior (AP) and lateral spine; P = 0.014 for the femoral neck; P = 0.004 for the trochanter], except the proximal radius (P = 0.065) and total body bone density (P = 0.069) after nafarelin therapy was stopped. In group 2, BMD increased significantly at the AP spine (P < 0.001), lateral spine (P = 0.012), femoral neck (P = 0.002), and trochanter (P = 0.029) after nafarelin therapy was stopped. BMD of the spine in the AP projection increased more in group 2 and than in group 1 after therapy was stopped (P = 0.045). Despite these increases after discontinuation of nafarelin therapy, BMD was still significantly below baseline values at the AP spine (P < 0.001) and femoral neck (P = 0.006) and tended to be lower than baseline values at the trochanter (P = 0.057) and total body (P = 0.101) at the end of the 1-yr follow-up period in group 1. In contrast, BMD was significantly above baseline values at the AP and lateral spine (P < 0.001) sites and was similar to baseline values at the other skeletal sites at the end of the 1-yr follow-up period in group 2. Bone turnover returned to baseline values in both groups when therapy was stopped. We conclude that the beneficial effects of PTH on bone persist in women who regain cyclic menstrual function. Although part of the increases in BMD are probably due to restoration of ovarian function, additional increases in BMD most likely represent a further anabolic effect of PTH on bone that is not detected until after PTH administration is stopped.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Endometriosis/tratamiento farmacológico , Nafarelina/uso terapéutico , Teriparatido/uso terapéutico , Adulto , Endometriosis/metabolismo , Femenino , Humanos , Nafarelina/administración & dosificación , Teriparatido/administración & dosificaciónRESUMEN
CONTEXT: Short-term intermittent administration of parathyroid hormone (PTH) prevents bone loss from the spine in women treated with a gonadotropin-releasing hormone (GnRH) analog. However, the effects of a longer period of PTH administration on bone mass in estrogen-deficient women, particularly on the hip and on cortical bone of the total body, are unknown. OBJECTIVE: To determine whether more prolonged PTH administration can prevent estrogen deficiency bone loss from the hip, spine, and total body in young women with endometriosis receiving GnRH analog (nafarelin acetate) therapy. DESIGN: Randomized controlled trial. SETTING: General Clinical Research Center of a tertiary care, university-affiliated hospital. PATIENTS: Forty-three women between the ages of 21 and 45 years with symptomatic endometriosis. INTERVENTION: Nafarelin alone (200 microg intranasally twice daily) or nafarelin plus human parathyroid hormone-(1-34) (hPTH-[1-34]) (40 microg subcutaneously daily). MAIN OUTCOME MEASURES: The primary end points were bone mineral density (BMD) of the anterior-posterior and lateral spine, femoral neck, trochanter, radial shaft, and total body at 12 months of treatment. RESULTS: In the women who received nafarelin alone, the mean (SEM) BMDs of the anterior-posterior spine, lateral spine, femoral neck, trochanter, and total body were 4.9% (0.6%) (P<.001), 4.9% (0.8%) (P<.001), 4.7% (1.1%) (P<.001), 4.3% (0.9%) (P<.001), and 2.0% (0.6%) (P= .003) lower than at baseline after 12 months of therapy. In contrast, coadministration of hPTH-(1-34) increased BMD of the anterior-posterior spine by 2.1% (1.1%) (P=.09) and lateral spine by 7.5% (1.9%) (P=.002) and prevented bone loss from the femoral neck, trochanter, and total body, despite severe estrogen deficiency. Radial shaft BMD did not change significantly in either group. Serum bone-specific alkaline phosphatase and osteocalcin concentrations and urinary excretion of hydroxyproline and deoxypyridinoline increased 2-fold to 3-fold during the first 6 to 9 months of therapy in the women who received nafarelin plus hPTH-(1-34) and then declined. Changes in urinary deoxypyridinolone excretion were strongly predictive (r= 0.85) of changes in spinal BMD in the women who received nafarelin plus hPTH-(1-34). CONCLUSIONS: Parathyroid hormone prevents bone loss from the proximal femur and total body and increases lumbar spinal BMD in young women with GnRH analog-induced estrogen deficiency.