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Biomedical subjects

E S Orwoll

Publications and source records attributed to E S Orwoll.

16 recordsLinked to original sources

Vertebral deformity in men.

Vertebral fracture is the most prevalent manifestation of osteoporosis in women, but there is very little information concerning vertebral fracture in men. These studies begin to determine the prevalence, radiographic character, and relationship to bone mineral density of vertebral deformity in men. A group of 144 white men aged 34-94 years (83% between 50 and 80 years) were studied. Thoracic and lumbar spine radiographs were obtained using standardized techniques, and morphometric measures of vertebrae (T6-L5) were obtained using a computerized digitization pad. Vertebral deformities (wedge, midbody, and crush) were identified using several criteria. In addition, a skeletal radiologist independently identified vertebral deformities, as well as vertebrae affected by epiphysitis (Scheuermann's disease), using classic radiographic criteria. Bone mineral density was measured at lumbar spine and proximal femoral sites using dual-photon absorptiometry. The prevalence of vertebral deformity was related to the criteria used for their identification. Utilizing vertebral-specific criteria (anterior/posterior or midbody/posterior vertebral height more than 3 SD below vertebral specific mean), 10% of subjects had vertebral deformity. Wedge deformity occurred primarily in thoracic vertebrae and were more common than midbody deformity, which occurred more commonly in lumbar vertebrae. Crush deformities were not observed. Evidence of vertebral epiphysitis was present in 9% of subjects but was not responsible for vertebral deformity sufficient to be falsely identified using the more than -3 SD criterion. Bone mineral density in subjects with vertebral deformity was clearly reduced at both vertebral (p = 0.003) and proximal femoral (p = 0.002) measurements sites. The number of vertebral deformities was negatively correlated with vertebral bone mineral density.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Longitudinal precision of dual-energy x-ray absorptiometry in a multicenter study. The Nafarelin/Bone Study Group.

Reproducibility is a key issue in both clinical and research applications of bone mineral density (BMD) measurements. To examine the longitudinal precision of dual-energy x-ray absorptiometry (DEXA) for the measurement of mineral density in vivo and in vitro, the performance of a group of instruments in the course of a multicenter longitudinal clinical trial was monitored. Measures were performed on eight identical machines (Hologic QDR1000) and analyzed using the same automated software program. Short-term precision was good in vitro, [anthropomorphic spine phantoms; mean intrasite coefficient of variation (CV) 0.42 +/- 0.1% (SD)] and in vivo (lumbar spine; CV 1.1 +/- 0.5%). Intersite measures of a single spine phantom (specified mineral content -57.8 g) revealed a range of 57.3-58.4 g (CV 0.7%). In two subjects intersite CV in vivo were 3.7 and 2.1% (spine) and 1.8 and 3.2% (femoral neck). At five sites frequent phantom measures were performed over a 1 year period (mean number of measures 196) and revealed a mean all-point CV of 0.43% (range 0.35-0.53%). Longitudinal precision in vivo was somewhat less (mean CV of spinal measures 1.1%, femoral neck 1.2%, trochanter 1.3%, and Ward's area 2.4%). At one additional site large variations in phantom measures heralded repeated mechanical failures that eventually required machine replacement. In summary, DEXA demonstrates good in vitro and in vivo longitudinal precision, providing the basis for expanded clinical and research usefulness. Nevertheless, stringent quality assurance measures are required to detect and respond to system malfunctions.

Absorptiometry, Photon

Androgen receptors in osteoblast-like cell lines.

Although androgens exert major effects on bone remodeling, the mechanisms by which they exert their effects remain unclear. Recently, it has become apparent that receptors for sex steroids may be present in osteoblastic cells. We have examined several cell lines with osteoblastic phenotypes to determine if specific, high affinity androgen receptors are present. Two cell lines of human origin (Saos-2 and U2-OS) and one of rat origin (UMR-106.01) were studied. Androgen binding sites were present in all cell lines. Binding affinities were high (KD = 1.6 - 2.5 x 10(-10) M), and similar to those in classical androgen target tissues (prostate, kidney). Concentrations were greater in the human cell lines (1277 and 1605 sites/cell) than in the rodent line (74 sites/cell). In the human cell lines androgen binding was also specific and typical of androgen receptors in other tissues. Specific estrogen binding was not present in the UMR-106.01 cells, and no estrogen receptors were detectable in the human cell lines using an enzyme-linked receptor immunoassay. Specific binding for progesterone was also absent in the UMR-106.01 cells, but progesterone receptors were detected immunologically in the Saos-2 (119 sites/cell) and U2-OS (118 sites/cell) lines. These findings indicate the presence of androgen receptors that are of similar character to those in classical androgen target tissues, and suggest that the study of these cell lines may be useful in the study of the regulation of androgen effects in osteoblasts.

Androgens

Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass.

The etiology of the racial disparity in bone mass and fracture rate is unknown. Since the PTH-vitamin D endocrine system is a major regulator of calcium metabolism and bone turnover, this cross-sectional study examined the relationship of radial and lumbar bone density to vitamin D metabolite and PTH concentrations and to calcium intake and excretion in 67 white and 70 black highly comparable, healthy, premenopausal women. Bone density at both radial and lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was slightly but not statistically significantly (P = 0.08), lower in blacks than in whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D concentration in blacks was well within the normal range and was not associated with evidence of secondary hyperparathyroidism. There were no correlations of bone density to vitamin D or PTH concentrations. Although there were no racial differences in dietary intake of calcium and vitamin D or in sodium excretion, 24-h urinary calcium excretion was significantly lower in blacks than in whites, and calcium excretion was inversely associated with radial bone density. In contrast to previous reports, in healthy, normal weight, premenopausal black women there is no evidence of vitamin D deficiency or secondary hyperparathyroidism, suggesting that factors other than the vitamin D-PTH axis are responsible for racial differences in bone mass.

Adult

The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation.

OBJECTIVE: To determine the rate of bone loss in normal men, and to examine the effects of dietary calcium and cholecalciferol supplementation on bone loss in men. DESIGN: Double-blinded, placebo-controlled 3-year trial of supplementation with calcium (1000 mg/d) and cholecalciferol (25 micrograms/d). SETTING: Clinical research center at a university medical facility. SUBJECTS: Normal men 30 to 87 years old, recruited from the Portland community. MEASUREMENTS AND MAIN RESULTS: Radial bone mineral content (assessed by single-photon absorptiometry) fell by 1.0%/y (95% CI, -1.3% to 0.7%) at a proximal radial site and 1.0%/y (95% CI, -1.4% to -0.6%) at a distal radial site. Vertebral bone mineral content (assessed by dual-energy quantitative computed tomography) declined by 2.3%/y (95% CI, -2.8% to -1.8%). In these healthy men with a high basal dietary calcium intake (1159 mg/d), calcium and cholecalciferol supplementation did not affect bone loss at any site. CONCLUSIONS: Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population.

Adult

Serum osteocalcin (BGP) levels in normal men: a longitudinal evaluation reveals an age-associated increase.

Serum levels of bone gla protein (BGP) have been reported to increase with aging and hence to reflect an age-related increase in bone remodeling activity. To evaluate the relationship between aging and serum BGP levels in a study of longitudinal design, we measured BGP concentrations in 77 normal men at 6 month intervals over a 3 year period. Mean BGP levels at the onset (4.95 +/- 1.5 ng/ml) increased significantly during the study (p = 0.004), and the mean of individual BGP slopes was positive (0.38 +/- 0.6 ng/ml per year, p = 0.0001). The rate of change in BGP was not related to serum creatinine levels or dietary calcium intake.

Adult

Influence of age and body weight on spine and femur bone mineral density in U.S. white men.

Bone mineral density (BMD) was measured in normal white males using 153 Gd dual-photon absorptiometry. Measurements were made on the lumbar spine (n = 315) and on the proximal femur (n = 282) utilizing three regions of interest. There was a small but significant age-related decrease in spinal BMD (r = -0.11; -0.001 g/cm2 per year) and trochanteric BMD (r = 0.27; -0.002 g/cm2 per year). The BMD of the other femoral sites decreased more rapidly; the femoral neck (r = -0.58; -0.005 g/cm2 per year) and Ward's triangle (r = -0.69; -0.007 g/cm2 per year) declined by about 21 and 34%, respectively, from age 20 to age 70. These femoral BMD decreases were three to four times greater than those usually seen in the peripheral skeleton in males but less than the decreases of 25-30 and 40% in the femoral neck and Ward's triangle of white females. This pattern of aging bone loss may partially explain the paucity of spine fractures and the lower incidence of hip fractures in males versus females.

Adult

Relationship of mineral metabolism and long-term calcium and cholecalciferol supplementation to blood pressure in normotensive men.

To better understand the effects of calcium and cholecalciferol supplementation on blood pressure, we examined systolic and diastolic blood pressures in 65 men treated with 1000 mg Ca/d and 1000 IU cholecalciferol/d or placebo for 3 y. Subjects were normotensive and had no medical condition and took no medication known to affect mineral metabolism or blood pressure. At baseline, systolic blood pressure was positively related to fasting calcium excretion and negatively to ionized calcium concentrations. Phosphorus concentrations (negatively) and fasting calcium excretion (positively) were correlated with diastolic pressures. Nevertheless, calcium and cholecalciferol supplementation did not influence blood pressure at any time during the study. These results suggest that whereas calcium metabolism may be related to the control of blood pressure, dietary calcium and cholecalciferol intakes do not play a major role in its regulation in normotensive individuals. Calcium and cholecalciferol supplements should not be expected to have an effect on blood pressure in normotensive populations.

Adult

The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men.

To evaluate the influence of extravertebral calcification on spinal bone density determinations, we measured lumbar vertebral density in 71 hospitalized and 58 normal men using dual photon absorptiometry. The extent of vascular and osteophytic calcification was graded from lateral lumbar radiographs. Fifty-five (43%) of the subjects had identifiable osteophytes, and 86 (67%) had vascular calcifications. Despite similar ages and weights in subjects with and without ostephytes, those with osteophytes had greater spinal density (1.34 vs. 1.17 g/cm2; P less than 0.001), and there was a strong correlation between osteophyte severity and spinal density (r = 0.41; P less than 0.00001). Proximal femoral density was not different in those with and without osteophytes. The distribution of osteophytes in this population was not random, and as a result, the presence of osteophytes obscured the the relationship of bone density to age as well as the comparison of hospitalized to normal men. Vascular calcification had a minimal effect on vertebral density. In summary, osteophytic calcification exerted an important influence on the measurement of spinal bone density in men. This effect should be considered in both clinical and research applications of integral vertebral density measures.

Absorptiometry, Photon

Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis.

To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis, we studied a group of 39 women aged 69 +/- 7 (standard deviation, SD) years with severe osteoporosis. The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis. No subject had risk factors for osteopenia other than their age and postmenopausal status, and no subject was receiving therapy for bone disease at the onset of the study. Subjects were followed for 2 years after randomization to receive either 1200 mg/day of calcium (as calcium carbonate) and 40 micrograms/day of 25-OHD (calcium-25-OHD group), or 1200 mg/day of calcium plus placebo (calcium-placebo group). Calcium-25-OHD resulted in a clear increase in 25-OHD levels (p less than 0.001) and an increase in calcium absorption as indicated by urinary calcium excretion. Nevertheless, there was no significant change in fasting serum calcium, phosphorus, alkaline phosphatase, PTH, or 1,25-(OH)2D in either group. Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period. Unexpectedly, repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups, presumably as a result of the calcium supplementation alone. In summary, calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia. The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The relationship of swimming exercise to bone mass in men and women.

Exercise appears to be capable of exerting a positive effect on bone mass, but how exercise can be used to best advantage in the prevention and therapy of osteopenia is unclear. Weight-bearing activity has been commonly considered to be essential for the beneficial effects of exercise on the skeleton, and, therefore, swimming has been considered valueless in the maintenance of bone mass. To examine this issue we measured radial and vertebral bone mineral density in a group of subjects aged 40 to 85 years who had been swimming regularly for at least 3 years as well as in a similar group of nonexercising control subjects. The swimmers engaged in no other forms of regular exercise, and no subject had other conditions known to affect bone or mineral metabolism. Dietary calcium and protein intakes were similar in the two groups. At both radial (0.84 +/- 0.08 vs 0.81 +/- 0.09 g/cm2) and vertebral (123 +/- 27 vs 108 +/- 31 mg/cm3) sites the male swimmers had significantly greater bone mineral density than did the nonexercisers. In women, however, no relationship of swimming to bone mineral density could be identified. These results suggest that swimming exercise may be beneficial in the prevention or therapy of osteopenia and that its usefulness in this regard should be further investigated.

Adult

Calcium and cholecalciferol: effects of small supplements in normal men.

The effect of small calcium and vitamin D supplements on mineral metabolism in normal persons is unclear. To investigate the biochemical response to these medications, we administered 1000 mg Ca and 25 micrograms cholecalciferol per day or a placebo to 92 normal men for 1 y. The Ca and cholecalciferol were tolerated well. 25-Hydroxycholecalciferol [25-(OH)D] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D] levels rose in treated subjects; there was no definite change in 1,25-(OH)2D concentrations. The average difference in 25-(OH)D levels between treated and untreated subjects was 30 nmol/L at 1 y. Fasting serum Ca, alkaline phosphatase, creatinine, and parathyroid hormone levels and the fasting urinary excretion of Ca, phosphorus and cAMP, were not affected. However, 24-h urinary Ca excretion was higher in the supplemented group (3.5 +/- 1.9 vs 4.7 +/- 1.7 mmol/d, p = 0.006). Serum P concentrations were slightly higher in the supplemented group at 1 y. In normal men small calcium and cholecalciferol supplements are safe, provide adequate vitamin D nutrition and apparently increase net gastrointestinal Ca absorption.

Adult

Dissociation of secretory responses to low-calcium and beta-adrenergic stimulation in primary hyperparathyroidism.

We have used a parathyroid cell perifusion system to evaluate the secretory responses to low-calcium and beta-adrenergic stimuli in series of 13 adenomatous human parathyroid tissues. In cells from all chief cell adenomas PTH secretion could be influenced by changes in extracellular calcium concentrations (either an increase in response to lower calcium concentrations or a decrease following an increase in calcium levels). However, there was marked heterogeneity in the PTH secretory response to adrenergic stimulation. In most instances, adenomatous parathyroid tissue also responded quickly and vigorously to beta-adrenergic agents (mean increase in secretion 322% +/- 52 (SEM) over baseline), although five of the 13 tissues clearly showed no PTH secretory response. Furthermore, there was a dissociation between the responses to adrenergic and low-calcium stimulation in that the presence or magnitude of the response to one type of stimulus could not be used to predict the nature of the response to the other. Studies of cells from an oxyphil adenoma revealed a very vigorous response to adrenergic stimulation (1,400% over baseline), but no response to changes in extracellular calcium concentrations. These results indicate that human parathyroid tissue is capable of a marked secretory response to adrenergic stimulation. The dissociation between secretory responses to low-calcium conditions and adrenergic agents suggests that the mechanisms of secretion by low-calcium and adrenergic stimuli in adenomatous human parathyroid tissue are to some degree independent. Furthermore, aberrancies in the neoplastic parathyroid process apparently may affect either of these two secretory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma

Interstitial pneumonia from mitomycin.

Pulmonary disease has been associated with several chemotherapeutic agents but has not been reported in patients receiving the alkylating agent mitomycin (Mutamycin). We describe here the cases of three patients who developed interstitial pneumonia while receiving mitomycin therapy. Their clinical features including dyspnea, cough, and occasionally fever; reticular infiltrates were seen on chest roentgenogram. Histologically, diffuse alveolar septal edema, mononuclear-cell interstitial infiltrates, hypertrophy of alveolar lining cells, and alveolar septal collagen deposition were characteristic. Treatment with corticosteroids was associated with a rapid therapeutic response in all three patients.

Female