RESUMEN
The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.
Asunto(s)
Dorso/fisiología , Músculo Esquelético/fisiología , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/prevención & control , Levantamiento de Peso/fisiología , Anciano , Análisis de Varianza , Densidad Ósea/fisiología , Distribución de Chi-Cuadrado , Ejercicio Físico/fisiología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Fracturas de la Columna Vertebral/diagnóstico por imagenRESUMEN
HYPOTHESIS: Results of reoperative parathyroid surgery (RPS) have improved with the advent of sestamibi parathyroid subtraction scanning and intraoperative parathyroid hormone (IOPTH) monitoring. DESIGN: Retrospective review of patient histories, preoperative localization studies, operative data, including IOPTH monitoring, and outcomes for patients undergoing recent RPS at a single institution. Follow-up was complete (mean, 20 months). SETTING: Tertiary care referral center. PATIENTS: All patients undergoing RPS for benign persistent or recurrent primary hyperparathyroidism during the period 1989 to 1997. MAIN OUTCOME MEASURES: Overall cure rate and operative morbidity from RPS; sensitivity and accuracy of preoperative localization studies; and prediction of cure from IOPTH monitoring. RESULTS: The study group included 124 patients (87 women and 37 men). Hypercalcemia was corrected in 109 patients (88%). Permanent recurrent laryngeal nerve injury occurred in 0.8% and permanent hypoparathyroidism in 13% of patients. Test sensitivities and accuracies, respectively, were as follows: ultrasound with biopsy, 90% and 82%; sestamibi parathyroid subtraction scanning, 82% and 67%; and ultrasound alone, 75% and 65%. Level of IOPTH was predictive of cure in all patients with a 70% or greater fall from baseline at 20 minutes after excision. Persistent multigland disease was the major cause for reoperative failure (73%). CONCLUSIONS: Neither cure rates nor operative morbidity have changed appreciably over the past 2 decades, despite the introduction of sestamibi parathyroid subtraction scanning and IOPTH monitoring. Multigland disease continues to represent the principal cause of failure in RPS despite the routine use of preoperative localization studies. Thus far, increasing the stringency of IOPTH monitoring from a 50% to 70% decline from baseline levels has been predictive of cure, even in multigland disease. Most missed abnormal glands reside in normal anatomic locations, and the need for multiple operations, not just the reoperation, results in the increased morbidity seen with RPS.
Asunto(s)
Hipertiroidismo/diagnóstico por imagen , Hipertiroidismo/cirugía , Monitoreo Intraoperatorio/métodos , Hormona Paratiroidea/sangre , Radiofármacos , Tecnecio Tc 99m Sestamibi , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Hipertiroidismo/sangre , Masculino , Persona de Mediana Edad , Cintigrafía , Reoperación , Estudios RetrospectivosRESUMEN
OBJECTIVE: To describe a patient with a mediastinal parathyroid carcinoma and hypercalcemia as well as to compare the features of parathyroid carcinoma with those of hypercalcemia due to other causes of primary hyperparathyroidism. METHODS: We present a case report and discuss the diagnosis and management of this rare tumor. RESULTS: In a 44-year-old man, severe hypercalcemia and normal findings on neck exploration led to referral and ultimate detection of an anterior mediastinal mass. Surgical resection and pathologic examination of the mass revealed a cystic parathyroid carcinoma. Subsequently, normalization of serum calcium and parathyroid hormone levels ensued. CONCLUSION: Parathyroid carcinoma as an alternative to the diagnosis of primary hyperparathyroidism should be considered in patients with dramatically increased serum calcium and parathyroid hormone levels at the time of initial examination. The mainstay of therapy for parathyroid carcinoma is complete surgical resection. Accurate preoperative localization of parathyroid carcinoma is helpful, especially in instances of reoperation or hypercalcemic crisis.
RESUMEN
BACKGROUND: Reports of increased mortality from cardiovascular disease and malignancy in primary hyperparathyroidism have been based primarily on patients who have undergone parathyroidectomy. In order to assess the true impact of primary hyperthyroidism on mortality in the general population, we assessed survival in a large inception cohort of Rochester, Minnesota residents with primary hyperparathyroidism initially diagnosed over a 28-year span, the majority of whom were followed with uncomplicated disease. METHODS: All Rochester residents with primary hyperparathyroidism first recognized in 1965 to 1992 were identified through the Rochester Epidemiology Project medical records linkage system. Included as cases were patients with pathologic confirmation of hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia for more than a year with no other cause. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. RESULTS: During the study period, 435 cases of primary hyperparathyroidism were identified. Altogether, parathyroid surgery was performed on 126 patients (29%), with a mean delay between the initial elevated serum calcium level and surgery of 3.3 years. Patients who underwent surgery had higher maximum serum calcium levels than the patients who were observed (mean+/-SD, 11.3+/-0.7 versus 10.7+/-0.4 mg/dL, P <0.00 1), but their mean ages were similar (54+/-16 versus 56+/-17 years). Overall survival in the patients with primary hyperthyroidism was better than expected (P=0.02), but by age-adjusted multivariate analysis, higher maximal serum calcium level was an independent predictor of mortality (RR=1.3 per mg/dL; 95% CI: 1.1-1.6; P <0.02). CONCLUSION: Overall survival is not adversely affected among unselected patients with mild primary HPT in the community, although patients with more severe disease, as manifested by higher serum calcium levels, may have an increased risk of death.
Asunto(s)
Hiperparatiroidismo/mortalidad , Vigilancia de la Población , Calcio/sangre , Causas de Muerte , Humanos , Hiperparatiroidismo/sangre , Hiperparatiroidismo/diagnóstico , Hiperparatiroidismo/cirugía , Minnesota/epidemiología , Hormona Paratiroidea/sangre , Riesgo , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: The introduction of routine measurement of serum calcium levels led to a sharp increase in the incidence of primary hyperparathyroidism in the early 1970s. OBJECTIVE: To evaluate the trends in the incidence of primary hyperparathyroidism since the mid-1970s. SETTING: Rochester and Olmsted County, Minnesota. DESIGN: Population-based descriptive study. PATIENTS: All residents of Rochester, Minnesota, who received an initial diagnosis of primary hyperparathyroidism between 1965 and 1992 were identified through the medical records linkage system of the Rochester Epidemiology Project. Included as persons having definite cases (92% of the total) were patients with pathologically confirmed hyperparathyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia that had lasted for more than a year and had no cause other than primary hyperparathyroidism. MEASUREMENTS: Incidence rates were calculated and directly standardized to the population structure of white persons in the United States in 1990. RESULTS: From 1965 to June 1974 (the prescreening era), the age- and sex-adjusted incidence of primary hyperparathyroidism in Rochester was 15 cases per 100,000 person-years. After measurement of calcium levels was added to the automated serum chemistry panel in July 1974, the incidence increased to 112 per 100,000 person-years in 1975 and then decreased somewhat, reflecting a sweeping effect. Despite improved case ascertainment, however, the incidence rate has continued to decrease; in 1992, the incidence was 4 per 100,000 person-years. A few patients had complications that might have been caused by hyperparathyroidism (22% between 1965 and June 1974 and 6% thereafter), and survival was not impaired in either period. The maximum serum calcium levels did not change (P = 0.15). CONCLUSIONS: The progressive decrease in the incidence of primary hyperparathyroidism is unexpected and suggests a significant change in the epidemiology of this disease.
Asunto(s)
Hiperparatiroidismo/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipercalcemia/epidemiología , Hiperparatiroidismo/sangre , Hiperparatiroidismo/complicaciones , Incidencia , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Distribución por SexoRESUMEN
The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.
Asunto(s)
Densidad Ósea/fisiología , Ejercicio Físico/fisiología , Fémur/fisiología , Músculos/fisiología , Aptitud Física , Columna Vertebral/fisiología , Adulto , Femenino , Fracturas Óseas/prevención & control , Humanos , Cooperación del Paciente , Análisis de Regresión , Factores de Riesgo , Factores de TiempoRESUMEN
In a 4-year controlled, prospective trial, histomorphometric analysis was used to compare the tissue-level skeletal effects of fluoride therapy in 43 postmenopausal women (75 mg NaF/day) with those of 35 matching placebo subjects; all subjects received 1500 mg/day elemental calcium supplement. In addition to an initial, baseline biopsy, a second biopsy was obtained after 6, 18, 30 or 48 months. Measurements were made on a third biopsy obtained from 8 subjects following at least 72 months of fluoride therapy. The change in cancellous bone volume or trabecular thickness in fluoride-treated subjects was not different from a change in placebo-treated subjects. However, paired analysis in the fluoride-treated subjects indicated that bone volume was increased between the first and second biopsies (p < 0.005). Both osteoid length and width were significantly increased in fluoride compared with placebo subjects; however, only the osteoid surface increased linearly (r = 0.63, p < 0.001). The mineral apposition rate and relative tetracycline-covered bone surface were not different between fluoride and placebo treatment, although they were decreased in both groups in the second biopsy. The tetracycline-covered bone surface returned to normal in the third biopsy. Definitive evidence for osteomalacia is a prolonged mineralization lag time, which following fluoride treatment was found to be increased 9-fold in the second biopsy and 4-fold in the third biopsy. Further evidence for osteomalacia was increased osteoid thickness by 6 months, evidence of focal areas of interstitial mineralization defects, and broad tetracycline labels of low fluorescence intensity. In the third biopsies, osteoclastic resorption was observed beneath osteoid seams. Fluoride therapy increased the cortical width compared with placebo treatment (p < 0.02), and increased the osteoid surface in Haversian canals, but did not change the osteoid width, resorption surface or cortical porosity. After an initial rise, serum fluoride levels remained constant, and the urine values fell slightly. The bone fluoride concentration rose throughout the treatment period, and was correlated with the change in osteoid-covered bone surface (r = 0.56, p < 0.001). Although we found definitive evidence for osteomalacia, the cause of the osteomalacia was not determined in this study. On the other hand, the presence of bone resorption beneath unmineralized osteoid and of osteocyte halos is suggestive of hyperparathyroidism. Thus, it is possible that the strong stimulus for bone formation brought about by fluoride therapy resulted in relative calcium deficiency.
Asunto(s)
Matriz Ósea/efectos de los fármacos , Fluoruros/uso terapéutico , Osteoporosis/tratamiento farmacológico , Anciano , Biopsia , Matriz Ósea/metabolismo , Calcio de la Dieta/administración & dosificación , Método Doble Ciego , Femenino , Fluoruros/farmacocinética , Humanos , Persona de Mediana Edad , Osteoporosis/metabolismo , Osteoporosis/patología , Estudios ProspectivosRESUMEN
Due to the lack of epidemiologic data on osteoporosis in the young, we identified all 22 Olmsted County, MN, residents aged 20-44 years when first diagnosed with established osteoporosis in 1976-1990. The overall age- and sex-adjusted incidence rate was 4.1 per 100,000 person-years (95% CI 2.4-5.9) with a female to male ratio of age-adjusted rates of 1.2:1. The majority represented secondary osteoporosis (12 steroid-induced, 3 postmenopausal, 2 delayed puberty, 2 anticonvulsant-induced, 2 gastrointestinal disease, 2 alcoholism, 1 anorexia nervosa, and 7 other etiologies; some individuals had more than one factor present) but two had idiopathic osteoporosis (incidence 0.4 per 100,000 person-years, 95% CI 0-0.9). To further characterize the patients with idiopathic osteoporosis, we also reviewed the entire Mayo Clinic experience with such patients from 1976 to 1990, regardless of residency. A total of 56 patients (30 female/26 male) were identified with a median age at diagnosis of 34 years. Only 8% were hypercalciuric at presentation. There was a preponderance of cancellous bone fractures (vertebral 81%, rib 37%, wrist 13%), although 13% did have hip fractures. Transiliac bone biopsies were available in 18 patients. As compared to age- and sex-matched controls, the osteoporotic subjects had a significant reduction in trabecular bone volume, cortical thickness, and mean wall thickness, the latter suggesting an abnormality in osteoblast function in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Osteoporosis/epidemiología , Absorciometría de Fotón , Adulto , Factores de Edad , Fenómenos Biomecánicos , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/epidemiología , Huesos/metabolismo , Huesos/patología , Huesos/fisiología , Calcio/orina , Femenino , Fracturas de Cadera/etiología , Humanos , Incidencia , Estudios Longitudinales , Masculino , Minnesota/epidemiología , Osteoblastos/fisiología , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Osteoporosis/etiología , Factores Sexuales , Fracturas de la Columna Vertebral/etiología , Traumatismos de la Muñeca/etiologíaRESUMEN
Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred.
Asunto(s)
Neoplasias Óseas/complicaciones , Displasia Fibrosa Ósea/complicaciones , Osteomalacia/etiología , Adolescente , Adulto , Anciano , Neoplasias Óseas/clasificación , Neoplasias Óseas/diagnóstico , Niño , Preescolar , Femenino , Displasia Fibrosa Ósea/clasificación , Displasia Fibrosa Ósea/diagnóstico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteomalacia/patologíaAsunto(s)
Riñón/metabolismo , Osteomalacia/metabolismo , Fosfatos/antagonistas & inhibidores , Animales , Transporte Biológico Activo , AMP Cíclico/metabolismo , Femenino , Histiocitoma Fibroso Benigno/complicaciones , Histiocitoma Fibroso Benigno/patología , Humanos , Hipofosfatemia/metabolismo , Persona de Mediana Edad , Osteomalacia/etiología , Hormona Paratiroidea/farmacología , Neoplasias de los Tejidos Blandos/complicaciones , Neoplasias de los Tejidos Blandos/patología , Células Tumorales CultivadasRESUMEN
In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF at 75 mg/day or placebo (both groups received supplementary calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional analyses and extended observations are now available on 50 women from the NaF group followed for up to 6 years of treatment. In these women, LS-BMD increased linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because during the 4 year trial the NaF dosage was decreased (because of side effects) in 54 of the 101 women randomized to NaF, dose-response relationships could be evaluated. For the entire study population, serum F level correlated directly with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2. Multivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of several variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increasing LS-BMD except when the higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fluoruro de Sodio/uso terapéutico , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares/efectos de los fármacos , Persona de Mediana Edad , Análisis Multivariante , Fluoruro de Sodio/administración & dosificación , Fluoruro de Sodio/farmacología , Fracturas de la Columna Vertebral/prevención & controlRESUMEN
Osteoporosis and fracturing are well-recognized manifestations of primary biliary cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that result in bone loss are poorly understood. We used dynamic histomorphometric techniques to measure tissue level rates of cancellous bone resorption, formation, and turnover in 12 premenopausal women with PBC and in 12 normal premenopausal women. We compared these values with estimates of bone resorption and formation obtained concurrently in the same subjects by radiocalcium kinetics and biochemical markers. Rates of bone turnover were analyzed as a function of a risk score that reflects the severity of hepatic disease and cholestasis (Mayo proportional-hazards model). Positive correlations were observed between tissue level and whole skeletal estimates of bone remodeling. At the remodeling site (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by PBC, but wall thickness was decreased. At the level of bone tissues, mean bone turnover was increased in PBC patients but varied widely and increased as hepatic disease and cholestasis worsened. We conclude that PBC causes a reduction in the volume of bone formed at the remodeling site and that the overall level of bone remodeling and turnover in PBC is strongly influenced by the severity of hepatic disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be decreased by therapeutic agents that slow bone turnover, and that further bone loss may be halted by liver transplantation.
Asunto(s)
Enfermedades Óseas Metabólicas/fisiopatología , Remodelación Ósea/fisiología , Cirrosis Hepática Biliar/fisiopatología , Adulto , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/metabolismo , Femenino , Humanos , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/metabolismo , Persona de Mediana EdadRESUMEN
This article discusses the regulation of serum phosphorus under normal conditions, focusing on the pathophysiology of acquired hypophosphatemia and its clinical manifestation. In addition, the clinical settings and conditions in which hypophosphatemia is likely to cause severe morbidity are emphasized.
Asunto(s)
Fosfatos/sangre , Trastornos del Metabolismo del Fósforo , Humanos , Trastornos del Metabolismo del Fósforo/complicaciones , Trastornos del Metabolismo del Fósforo/etiología , Trastornos del Metabolismo del Fósforo/metabolismoRESUMEN
OBJECTIVE: To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN: Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING: Referral-based outpatient clinic. PATIENTS: Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS: Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS: Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS: Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS: Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.
Asunto(s)
Estradiol/administración & dosificación , Osteoporosis Posmenopáusica/tratamiento farmacológico , Administración Cutánea , Administración Oral , Anciano , Densidad Ósea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Estradiol/efectos adversos , Estradiol/sangre , Estrona/sangre , Femenino , Humanos , Medroxiprogesterona/administración & dosificación , Medroxiprogesterona/análogos & derivados , Acetato de Medroxiprogesterona , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Estudios Prospectivos , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/prevención & controlRESUMEN
Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.
Asunto(s)
Cirrosis Hepática Biliar/complicaciones , Trasplante de Hígado , Osteoporosis/etiología , Enfermedades de la Columna Vertebral/etiología , Absorciometría de Fotón , Femenino , Humanos , Cirrosis Hepática Biliar/fisiopatología , Persona de Mediana Edad , Osteoporosis/diagnóstico , Periodo Posoperatorio , Enfermedades de la Columna Vertebral/diagnósticoRESUMEN
The effect of acetylsalicylic acid (aspirin) on bone mass and bone prostaglandin E (PGE) in immobilization osteoporosis was studied in 12 growing dogs using a unilateral hind limb cast-fixation model. Osteoporosis was induced by fiberglass-cast immobilization of the right hind limb for 4 weeks, with the left hind limb as a control. Six dogs received buffered aspirin at 25 mg/kg body weight per os every 8 hours; 6 dogs received no treatment. All the dogs were killed after 4 weeks, and bone samples were collected. Bone mineral content of the distal tibial metaphysis was measured by single-photon absorptiometry. In vitro release of PGE from the calcaneus, tibial cortical bone, tibial cancellous bone, and ilium were measured using a specific radioimmunoassay for PGE. Compared with the controls, the casted limb of untreated dogs had half the bone mass and a twofold increase in bone PGE. Aspirin treatment was associated with a 65 percent reduction in bone PGE and a 13 percent bone mass sparing effect. These results provide indirect evidence that PGE plays a role in immobilization osteoporosis.
Asunto(s)
Aspirina/farmacología , Huesos/química , Inmovilización , Osteoporosis/prevención & control , Prostaglandinas E/análisis , Absorciometría de Fotón , Fosfatasa Alcalina/sangre , Animales , Aspirina/administración & dosificación , Huesos/efectos de los fármacos , Calcio/sangre , Perros , Femenino , Minerales/análisis , Osteoporosis/etiología , Hormona Paratiroidea/sangre , Fosfatos/sangre , Factores de TiempoRESUMEN
Forty-eight dialysis patients undergoing bone biopsy were analyzed for clinical history, blood biochemical values, bone histologic findings, bone aluminum content (BAC), bone iron content (BIC), bone iron stores, and histochemical staining of bone aluminum and bone iron. Four patients had significant trabecular bone iron staining alone; eight patients had significant bone iron and bone aluminum staining; 13 patients had significant bone aluminum staining alone; and 23 patients showed no significant bone aluminum or iron staining. Patients with significant bone iron staining were younger (37.4 +/- 5.3 years v 53.2 +/- 2.3 years, P less than 0.01, mean +/- SEM) and were more likely to be anephric (P less than 0.001) and to have a history of prior renal transplantation (P less than 0.10). The 12 patients with significant bone iron staining had received more blood transfusions than those without bone iron staining (96 +/- 22.8 U v 22 +/- 5.8 U, P less than 0.005). Patients with bone iron accumulation had higher levels of serum ferritin (3,594 +/- 1,138.4 micrograms/L [ng/mL] v 265 +/- 60.1 micrograms/L, P less than 0.01) and lower levels of immunoreactive parathyroid hormone (iPTH) (349 +/- 150 microLEq/mL v 1,801 +/- 397 microLEq/mL [386 +/- 166 pmol/L v 1,990 +/- 439 pmol/L], P less than 0.005). BIC was also higher in these patients (1,008 +/- 149 micrograms iron/g bone v 300 +/- 46.5 micrograms iron/g bone, P less than 0.001) and higher than normal BIC (256 +/- 44.2 micrograms iron/g bone, eight normals). Bone marrow iron stores were positively related to serum ferritin levels (P less than 0.01) and trabecular bone iron staining (P less than 0.10). All 13 patients with osteomalacia demonstrated significant bone aluminum staining; seven of these patients demonstrated concomitant significant iron staining. Fourteen of 15 patients with severe hyperparathyroidism showed no significant iron or aluminum staining. Our data indicate that iron will probably not accumulate within bone until all other storage sites (eg, bone marrow) are fully saturated. The presence of lower levels of iPTH in iron-overloaded patients raises the possibility that iron overload may induce a state of relative hypoparathyroidism. The most important determinant for the presence of osteomalacia seems to be the presence of significant aluminum staining. No specific bone histologic finding was related to the presence of bone iron staining, but the rarity of isolated significant bone iron staining makes it difficult to evaluate bone histologic diagnoses that might be solely attributable to iron.
Asunto(s)
Enfermedades Óseas Metabólicas/patología , Hierro/metabolismo , Diálisis Renal , Adulto , Aluminio/metabolismo , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Médula Ósea/metabolismo , Huesos/metabolismo , Huesos/patología , Femenino , Ferritinas/sangre , Histocitoquímica , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversosRESUMEN
The concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 microns thick sections of the bodies of the second lumbar vertebrae from six men (aged 21-58 years) and seven women (aged 25-58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer-assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellous bone.
Asunto(s)
Vértebras Lumbares/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Absorciometría de Fotón , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Cintigrafía , Reproducibilidad de los Resultados , Factores SexualesRESUMEN
To define the role of parathyroid gland function in the pathophysiology of bone loss in type I (postmenopausal) osteoporosis, we measured serum intact parathyroid hormone (PTH) concentration by immunoradiometric assay (IRMA) and by multisite immunochemiluminometric assay (ICMA) in 63 postmenopausal osteoporotic women (PMOp) with vertebral compression fractures and in 75 age-comparable postmenopausal normal women (PMNl). Also, tetracycline-based histomorphometric indices in cancellous bone were assessed in iliac biopsy samples from 61 PMOp and 28 PMNl women. Serum PTH concentrations by IRMA were similar in PMOp and PMNl (medians, 3.92 and 3.77 pmol/l; NS) but were significantly lower in PMOp by the more sensitive ICMA (medians, 2.82 and 3.14 pmol/l; P less than 0.01). By multiple linear regression analysis, serum PTH was directly related (P less than 0.001) to activation frequency, bone resorption rate, bone formation rate, and the calculated rate of bone loss. For each unit (pmol/l) increase in serum PTH by ICMA, activation frequency increased by 1.3%/year more (P = 0.01), bone resorption rate increased by 3.9%/year more (P = 0.003), and the rate of cancellous bone loss was 2.8% greater (P = 0.0003) in the PMOp women compared with the PMNl women. Concentrations of serum estradiol, but not serum estrone, had a weak opposing effect to PTH, especially for bone formation rate. These data suggest that in PMOp the bone has increased sensitivity to the biologic effects of PTH. This may represent one of the fundamental pathophysiologic defects in PMOp and, in the setting of estrogen deficiency, may explain, in part, their greater rate of bone loss.
Asunto(s)
Remodelación Ósea/fisiología , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/fisiopatología , Hormona Paratiroidea/sangre , Anciano , Estrógenos/sangre , Femenino , Humanos , Ensayo Inmunorradiométrico , Mediciones Luminiscentes , Persona de Mediana EdadRESUMEN
The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age +/- SD, 66 +/- 6 years) and in 32 carefully selected normal postmenopausal women (64 +/- 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P less than 0.05) at the cellular level and by 67% (P less than 0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P less than 0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P less than 0.001) was probably exacerbated by a 45% increase (P less than 0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1% year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.