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J C Gallagher

Publications and source records attributed to J C Gallagher.

At least 37 records · Page 2Linked to original sources

Dietary calcium and vitamin D intake in elderly women: effect on serum parathyroid hormone and vitamin D metabolites.

In this study, the effect of dietary calcium and vitamin D on serum parathyroid hormone and vitamin D metabolites was measured in 376 free-living women aged 65-77 y. Mean calcium intake in both groups was close to the recommended dietary allowance of 800 mg/d. Mean vitamin D intake in the 245 women not taking vitamin D supplements was 3.53 microg/d (141 IU/d), which is below the recommended dietary allowance of 5 microg/d (200 IU/d). To test the hypothesis that vitamin D is more important than calcium in reducing serum parathyroid hormone, the source of dietary calcium intake was subdivided into milk, which is fortified with vitamin D, and nonmilk sources. The serum parathyroid hormone concentration was inversely correlated with calcium intake derived from milk (r = -0.20, P < 0.01) but not from nonmilk sources (r = -0.06). Furthermore, serum calcidiol correlated with milk calcium intake (r = 0.35, P < 0.001) but not with nonmilk calcium intake (r = 0.10). Multivariate analysis showed a significant effect of season on serum calcidiol but not on serum parathyroid hormone. Serum parathyroid hormone was inversely correlated with serum calcidiol (r = -0.33, P < 0.001) and the regression predicted that mean serum parathyroid hormone would be reduced in the elderly to concentrations considered normal in the young when serum calcidiol is 122 nmol/L (49 ng/mL); this would require a much higher recommended dietary allowance for vitamin D than 5 microg/d (200 IU/d).

Aged↗

Bone density, bone turnover, and hormone levels in men over age 75.

BACKGROUND: Osteoporosis is a substantial problem in older men, with 25% of all hip fractures occurring in men. The mechanisms of bone loss in older men are unknown, but elevated parathyroid hormone (PTH) and diminished testosterone (T) levels are postulated as contributing factors. METHODS: We measured bone mineral density (BMD), sex hormones, bone turnover markers, and calcium regulating hormones in a group of community-living men over the age of 75. RESULTS: Thirty-five men (mean age 79; range 75-88 years) without disease or medication known to affect bone metabolism participated in the study. Whole body BMD was 1.21+/-.15 g/cm2; lumbar spine BMD (L1-L4) was 1.10+/-.15 g/cm2; femoral neck BMD was .77+/-.14 g/cm2; and trochanteric region was .71+/-.13 g/cm2. The femoral neck and trochanteric region values were more than 1 SD below the mean for adult men (age 25-33 years) in 28/35 and 15/35 men, respectively. Deoxypyridinoline levels were above the normal range for premenopausal women in 23% of the men; N-telopeptide and C-telopeptide demonstrated a wide scatter, but the values remained in the normal range. T levels were found to be below normal range for adult men in 12 of 32 (38%) subjects and the PTH levels above the normal range in 8 of 35 (23%) subjects. Bone resorption markers correlated inversely with BMD of the whole body, femur, and spine (r=-.22 to -.48). There was an inverse correlation between total T and spine BMD which became insignificant after correcting for body mass index (BMI). In addition, there was no correlation between free or bioavailable testosterone and BMD. 1,25-(OH)2D levels correlated inversely with BMD at the femur and whole body, but no association was found with PTH or 25 OH-D. CONCLUSIONS: Men over 75 years of age had a wide range of BMD but frequently had low values at femoral sites. T levels were below the normal range in 38% of men, and PTH levels were elevated in 23% of men. There was an inverse correlation between total T and spine BMD which may have been dependent on the common effect of BMI. Bone mineral density was inversely related to markers of bone resorption.

Aged↗

Calciotropic hormones and bone markers in the elderly.

There is a lack of substantial data on changes in calciotropic hormones and bone markers in elderly subjects living in North America. Parathyroid hormone (PTH), serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women) aged 65-87 years. There was a significant increase in serum osteocalcin and urine N-telopeptide with age in men, and a significant increase in serum osteocalcin with age in women. Serum PTH and 25(OH)D showed no significant change with age in men or women. After adjusting for age, calcium intake, serum creatinine, season, and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum 25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than women. Serum PTH was correlated with serum osteocalcin in men and women, r = 0.24, r = 0.17, p < 0.001, but not with urine N-telopeptide. Serum PTH was inversely correlated with serum 25(OH)D (r = -0.25, r = -034,p < 0.001), and positively correlated with serum creatinine (r = 0.14, r = 0.17,p < 0.01) in men and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 33% in females and 0.4% in men. Thus vitamin D deficiency was very uncommon in the U.S.A. compared with Europe. Although mean serum PTH was increased in the elderly, only 4-6% had PTH levels above the normal range. In summary, the increase in serum PTH in the elderly can be explained more by changes in vitamin D status than by declining renal function. These data also show significantly higher (p = 0.001) bone remodeling markers in women.

Age Factors↗

Effect of vitamin D receptor genotypes on calcium absorption, duodenal vitamin D receptor concentration, and serum 1,25 dihydroxyvitamin D levels in normal women.

It is well established that bone mineral density is under strong genetic control. Recently it was reported that the Bsm I restriction fragment length polymorphism of the vitamin D receptor (VDR) gene could account for up to 75% of the genetic variance in bone mineral density. However, the physiological basis for such an effect has not been established. The VDR gene codes for the vitamin D receptor protein which regulates intestinal calcium absorption. In order to assess the biochemical basis we studied the effect of common allelic variation of the VDR gene on intestinal VDR protein concentration, calcium absorption, and serum 1,25 dihydroxyvitamin D (1,25(OH)2D). Ninety-two Caucasian women were genotyped for Bsm I and Taq I polymorphism at the VDR gene locus. From these we compared 49 young women aged 25-35 years and 43 elderly women aged 65-83 years, who had all three measurements performed. There were no significant differences in intestinal VDR protein concentration, serum 1, 25(OH)2D, or radioactive calcium absorption among VDR genotype groups. Therefore, the small intestine does not seem to be a target for VDR gene polymorphism.

Absorption↗

Serum vitamin D metabolites and calcium absorption in normal young and elderly free-living women and in women living in nursing homes.

Vitamin D deficiency, which causes osteomalacia, may also be important in the pathogenesis of age-related osteoporosis. We studied serum vitamin D metabolites in 52 young women (mean age: 30 +/- 3 y; range: 25-35 y), 64 elderly free-living women (mean age: 71 +/- 4 y; range: 65-82 y), and 60 elderly women living in nursing homes (mean age: 84 +/- 9 y; range: 61-102 y). Mean serum 25-hydroxyvitamin D (calcidiol) was 10.8 +/- 4.4 nmol/L (27 +/- 11 ng/mL) in women living in nursing homes and was similar to that of free-living young (11.3 +/- 4.2 nmol/L, or 28 +/- 10 ng/mL) and elderly (11.5 +/- 3.2 nmol/L, or 29 +/- 8 ng/mL) women. Vitamin D deficiency (defined as serum calcidiol < 4.8 nmol/L, or 12 ng/mL) occurred in 8% of women living in nursing homes, in 6% of the young women, and in 1.6% of the free-living elderly women. Serum calcidiol was significantly correlated with vitamin D intake (r = 0.25, P < 0.05) and inversely correlated with serum intact parathyroid hormone (iPTH) (r = -0.16, P < 0.03). Serum iPTH increased with age and secondary hyperparathyroidism was observed in 17% of the women living in nursing homes. Calcium absorption declined with age, but calcium absorption and serum 1 alpha,25-dihydroxyvitamin D (calcitriol) were significantly lower in women living in nursing homes, which probably contributed to the secondary hyperparathyroidism. In conclusion, normal serum calcidiol may avoid the problem of osteomalacia, but it does not correct malabsorption of calcium. Although calcitriol corrects the malabsorption of calcium, it remains to be seen whether higher amounts of vitamin D can normalize the calcium malabsorption of aging.

Adult↗

Bone mineral density and biochemical markers of bone turnover in healthy elderly men and women.

BACKGROUND: Osteoporosis risk in middle-aged women is twofold greater than that in men, and the difference increases with age. Gender differences in bone mineral density, estimated rates of bone loss, and usefulness of markers of bone metabolism for predicting bone density have not been well described in healthy elders aged 65 and above. The purpose of this cross-sectional analysis was to describe associations of bone mineral density at the hip, spine, and whole body with age, serum osteocalcin, and urinary N-telopeptide crosslinks of Type I collagen in healthy elderly men and women. METHODS: A total of 1,087 healthy adults (273 men and 814 women) aged 65 to 87 years were enrolled in a collaborative study at 3 sites: Tufts University (Boston, MA), University of Connecticut Health Center (Farmington, CT), and Creighton University (Omaha, NE). Bone mineral density (BMD) at three regions of the hip, the lumbar spine, and whole body was determined by dual-energy x-ray absorptiometry. Serum osteocalcin was measured by immunoassay, and measurement of N-telopeptide crosslinks (Ntx) in urine was made using an enzyme-linked radioimmunoassay (ELISA). RESULTS: Among women, the age-related decline in BMD at all non-spine skeletal sites was significantly different from zero, with the largest decline seen at the femoral neck (-.0038 g/cm2/y, p < .001) and the smallest at the trochanter of the hip (-.0023 g/cm2/y, p = .03). Among men, the changes at all non-spine sites were not significant. In both sexes, spine BMD tended to increase with age (men, +.0045 g/cm2/y, women, +.0003 g/cm2/y). Serum osteocalcin and urinary Ntx were inversely related to BMD at all skeletal sites, but the weakest associations were observed at the spine. Individuals whose values of both osteocalcin and Ntx were in the lowest quartiles of the respective sex-specific distributions had mean femoral neck BMD that were 11% higher than individuals with marker values in the highest quartiles. CONCLUSIONS: These findings suggest that age-related decreases in BMD may vary by gender and skeletal site. Determinations of osteocalcin and N-telopeptide crosslinks at a single point in time may potentially be used as indicators of current bone status, particularly at non-spine skeletal sites.

Aged↗

Association between intestinal vitamin D receptor, calcium absorption, and serum 1,25 dihydroxyvitamin D in normal young and elderly women.

The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

Adult↗

Effect of parathyroid hormone (hPTH[1-34]) infusion on serum 1,25-dihydroxyvitamin D and parathyroid hormone in normal women.

Calcium absorption declines with age. Because 1,25-dihydroxyvitamin D (1,25(OH)2D) is the major hormone controlling calcium absorption, changes in vitamin D metabolism may account for the malabsorption of aging. Serum levels of 1,25(OH)2D have been reported to either decrease or remain unchanged with age. To assess the effect of aging on renal production of 1,25(OH)2D, we evaluated the response of renal 25OHD 1 alpha hydroxylase to human parathyroid hormone (hPTH(1-34) stimulation in 119 women ages 25-83 years. In this population, baseline serum 25OHD and 1,25(OH)2D values did not significantly change with age, but serum iPTH (r = 0.44; p < 0.001) and serum creatinine (r = 0.31; p < 0.01) increased with age. However, the stimulatory activity of hPTH(1-34) on the renal production of 1,25(OH)2D declined with age (r3 = -0.36; p < 0.001) and was most apparent after age 75, being 50% less than that of younger women. Besides age, the production of 1,25(OH)2D was found to be dependent on baseline serum iPTH (r = -0.31; p < 0.0001). Administration of hPTH(1-34) led to suppression of endogenous PTH, and suppressibility of endogenous PTH declined with age (r = 0.53; p < 0.0001). The increase in serum PTH and decreased suppressibility of PTH with age could be due to mild secondary hyperparathyroidism. The increase in PTH with age is probably responsible for maintaining normal serum 1,25(OH)2D levels in elderly subjects; however, decreased metabolism of 1,25(OH)2D in the elderly could also maintain normal serum 1,25(OH)2D levels.

Adult↗

The role of vitamin D in the pathogenesis and treatment of osteoporosis.

It is well recognized that patients with postmenopausal osteoporosis usually exhibit some degree of calcium malabsorption and commonly have low serum concentrations of 1,25-dihydroxyvitamin D (calcitriol). Administration of calcitriol has been shown to normalize calcium absorption in patients with osteoporosis and, over the long term may have a stimulating effect on bone formation. Clinical trials have shown a significant reduction in osteoporotic fractures among calcitriol-treated patients. Hypercalcemia and hypercalciuria are infrequent complications of calcitriol therapy with physiologic doses (0.25 microgram twice daily), and are most commonly related to excessive calcium intake (i.e., > 1000 mg daily).

Adult↗

Effect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern.

PURPOSE: To measure changes and predictors of change in mammograms obtained in postmenopausal women undergoing continuous combined hormonal replacement therapy (HRT). MATERIALS AND METHODS: Mammograms of 41 postmenopausal women obtained before and 1 year after the initiation of HRT were evaluated blindly according to the quantitative density percentage method and the Wolfe classification system. RESULTS: Mammographic densities increased compared with baseline values in 73% of subjects (mean increase, 6.7%; 95% confidence interval, 2.5%, 11.0%; P = .003). A shift in Wolfe classification from lower to greater parenchymal density was noted in 24% of subjects (P = .016). Multivariate analysis results indicated that the lower the tissue density percentage before treatment, the greater the increase in density percentage after treatment. CONCLUSION: An increase in mammographic density was demonstrated in most subjects undergoing continuous combined HRT and was most pronounced in subjects with a lower baseline density percentage.

Breast↗

Effects of increasing doses of 1 alpha-hydroxyvitamin D2 on calcium homeostasis in postmenopausal osteopenic women.

This study is the first reported administration of 1 alpha-hydroxyvitamin D2 (1 alpha-OHD2) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1 alpha-OHD2, beginning with a low dose of 0.5 microgram/day. In 15 subjects, the doses were raised at weekly intervals to 1.0, 2.0, 4.0, and 5.0 micrograms/day, and in 5 of these subjects, the dose was further increased to 8.0 or 10.0 micrograms/day. Mean urine calcium +/- SEM showed a dose-related increase from 134 +/- 17 mg/24 h on 0.5 microgram/day to 198 +/- 21 mg/24 h on 4.0 micrograms/day (p < 0.05) and to 241 +/- 35 mg/24 h on 5.0 micrograms/day (p < 0.05). No subjects had hypercalciuria (> 350 mg/24 h, the upper limit of the laboratory normal range) at doses less than 5.0 micrograms/day; 5 subjects had hypercalciuria at or above 5.0 micrograms/day (3 at 5.0 micrograms/day, 1 at 8.0 micrograms/day, and 1 at 10.0 micrograms/day). Mean serum calcium increased slightly on the 4.0 micrograms dose only (p < 0.05) but remained well within the normal range. Mean creatinine clearance and BUN, used as measures of renal function, showed no significant changes. Routine blood and urine assays also showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Bone mineral density in normal and asthmatic children.

BACKGROUND: The largest increase in bone mass occurs during childhood and adolescence. A subnormal bone mass is associated with increased risk of fracture. Bone mass is influenced by height, age, race, exercise, and stage of puberty. It is adversely affected by chronic disease states and corticosteroid use. We performed a cross-sectional study of bone density in children with moderate to severe asthma who were treated with inhaled corticosteroids, inhaled cromolyn, oral corticosteroids, or a combination of these, and we compared them with normal children. METHODS: A cross-sectional study of bone density, measured either by dual-photon or dual-energy absorptiometry, was performed on 97 normal white and 30 asthmatic white children, aged 5 to 18. Average daily calcium intake, height, weight, and Tanner stage were determined. The total daily and lifetime doses of inhaled corticosteroids in children with asthma were calculated. T tests, multiple regression, chi square analysis, and analysis of covariance were performed. RESULTS: No significant difference in bone density was demonstrated between children with asthma and normal control subjects. No measure (including calcium intake, Tanner stage, daily or lifetime inhaled corticosteroid dose, or duration of illness), except for height and age, provided a significant contribution to the explanation of bone density in children with asthma. CONCLUSION: Children and adolescents with moderate to severe asthma, including those treated with inhaled corticosteroids, do not appear to have adversely affected bone mass. There was, however, the possibility of a type II error in this study because of the sample size.

Absorptiometry, Photon↗

Influence of isotonic, isometric and isokinetic muscle strength on bone mineral density of the spine and femur in young women.

Bone mineral density (BMD) is dependent on multiple influences including genetics, mechanical forces, hormonal changes and nutritional mechanisms. The mechanical forces are, in part, influenced by muscle strength. This study examined the relationships between BMD of the spine and femur with muscle strength. Eighty-one healthy, non-athletic women aged 20-30 years were the subjects in the study. BMD was measured by dual energy x-ray absorptiometry. Trunk strength was measured by a Wagner Dynamometer or a Cable Tensiometer and leg strength was measured with a Cybex II isokinetic dynamometer. Trunk, leg and hip strength was also measured using 1 RM (one repetition maximum). There were significant correlations between spine density and trunk extension (r = 0.40, P = 0.0001) and spine density and trunk flexion (r = 0.30, P = 0.0037). There were significant correlations between femoral neck density and knee extension (r = 0.40, P = 0.003) and femoral neck density and knee flexion (r = 0.24, P = 0.0240). Multiple regression analysis showed that amongst young adult females weight and trunk extensor muscle strength contributed about equally to spine density. Flexor muscle strength did not influence bone density.

Absorptiometry, Photon↗

Thalassemia minor: a risk factor for osteoporosis?

A case report of a 53 year old postmenopausal woman with severe osteoporosis occurring in association with beta thalassemia trait is presented. She was found to have marked axial osteopenia with lumbar spine bone mineral density that was more than three standard deviations below the mean, but had normal bone mineral density of the proximal radius. A biopsy of the iliac crest showed evidence of high turnover osteoporosis. Bone densitometry of the spine and hip in a consecutive series of eleven asymptomatic individuals with thalassemia trait also is reported. Bone mineral density was diminished in the spine (z-score = -0.78, P less than 0.03) and hip (z-score = -0.54, P = 0.05) of patients with thalassemia trait. It is postulated that thalassemia minor may be a risk factor for osteoporosis.

Adult↗

Vitamin D metabolism and therapy in elderly subjects.

Serum 25-hydroxyvitamin D declines in elderly subjects. This decrease reflects, in part, a lower vitamin D intake. But changes in serum 25-hydroxyvitamin D are more marked in the northern latitudes of the world because less vitamin D synthesis occurs n the skin as a result of a reduced amount of ultraviolet light. Consequently, vitamin D deficiency leading to osteomalacia is more common in thr northern latitudes, particularly among the elderly. The Recommended Daily Allowance of 200 IU of vitamin D in the elderly may be insufficient, since higher doses of 800 IU/day have been shown to reduce the incidence of osteoporotic fractures. The use of more potent analogues of vitamin D, such as calcitriol (Rocaltrol), should be reserved only for those patients who have established vertebral osteoporosis and who generally have more pronounced malabsorption of calcium.

Aged↗

Effect of progestin therapy on cortical and trabecular bone: comparison with estrogen.

PURPOSE: To determine the effect of progestin therapy on bone mineral density in postmenopausal women and to compare its effects to those of estrogen. SUBJECTS AND METHODS: A prospective, randomized clinical trial was performed in 81 postmenopausal women aged 51.7 +/- 4.4 years (mean +/- SD). They were assigned to one of four groups: Provera 20 mg, Premarin 0.6 mg, Premarin 0.3 mg plus Provera 10 mg, and a placebo. In addition, all women received calcium supplementation, if necessary, to a calcium intake of 1,000 mg/day. We used single- and dual-photon absorpiometry, metacarpal radiogrammetry, and computed axial tomography to measure bone mineral density in the total skeleton, spine, radius, and metacarpal. RESULTS: Women receiving placebo lost bone at all sites (p less than 0.01). The Provera-treated group showed no change in total body calcium, but there were decreases in radial density (p less than 0.01), metacarpal cortex (p less than 0.01), and spine density (p less than 0.01). The Premarin-treated group had an increase in spine density and total body density (p less than 0.05), but a decrease in radial density (p less than 0.05). The Premarin-plus-Provera group showed no change in spine density, total body calcium, or radial density but had a decrease in metacarpal cortex (p less than 0.01). CONCLUSIONS: Compared to placebo, Provera reduced the rate of loss in cortical areas of the skeleton, but not in the spine, which contains more trabecular bone. In contrast, Premarin reduced the rate of loss in both cortical and trabecular areas of the skeleton. The low-dose combination of Premarin plus Provera was similar in its effect on bone to that of Premarin alone, suggesting that there may be a synergistic effect of this hormone combination on bone. Serum cholesterol levels decreased with Provera, Premarin, and the combination of both, whereas levels of serum triglycerides increased with Premarin treatment, decreased with the Provera regimen, and were unchanged with the combination therapy. Provera does not adversely affect the lipid profile.

Bone Density↗