Search PubMed⌕ Search

Biomedical subjects

J C Gallagher

Publications and source records attributed to J C Gallagher.

At least 55 records · Page 3Linked to original sources

The effects of estrone (Ogen) on spinal bone density of postmenopausal women.

The effects of cyclical treatment with estrone sulfate (0.3, 0.625, or 1.25 mg), plus calcium carbonate, on spinal trabecular bone density were compared with placebo in 120 postmenopausal women in this 2-year, multicenter, double-blind study. While the placebo and 0.3-mg treatment groups lost bone density (-3.6% and -5.1%), the 0.625- and 1.25-mg treatment groups experienced no significant change from baseline at 24 months (-0.8% and +0.7%). The 1.25-mg treatment group was significantly different from the placebo group at 12, 18, and 24 months. Although the 0.625-mg treatment group was significantly different from the placebo group only at 18 months, the data suggest that 0.625 and 1.25 mg of estrone sulfate had different effects than placebo and 0.3 mg of estrone sulfate and, given with supplemental calcium, are effective doses for the prevention of spinal bone loss.

Bone Density↗

Estimation of bone mineral density in children with juvenile rheumatoid arthritis.

Bone mineral content of different areas of the skeleton was measured by dual photon absorptiometry in 20 children with juvenile rheumatoid arthritis (JRA) and compared to 20 age and sex matched healthy children. Spinal density was similar in both groups in prepubertal children but decreased in the postpubertal girls with JRA. Total bone density was also decreased in the postpubertal girls. Six children with JRA had repeat scans 12 to 24 months later; in 3 children total bone mineral content increased significantly with an intensive management program. Our study suggests that bone mineral density does not show a pubertal increase in children with JRA, as it does in healthy children.

Absorptiometry, Photon↗

Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study.

OBJECTIVE: To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 (calcitriol) in the treatment of osteoporosis. DESIGN: Two-year, double-blind, randomized clinical trial. SETTING: University medical center. PATIENTS: Fifty postmenopausal women with vertebral fractures recruited by referral. INTERVENTION: Calcium intake was adjusted to 25 mmol/d (1000 mg/d) at baseline. Patients were then randomized to treatment with either calcitriol or placebo. During the study, calcium intake was reduced to 15 mmol/d (600 mg/d) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L (less than 11.0 mg/dL) or urine calcium less than 9.96 mmol/d (less than 400 mg/d). MEASUREMENTS AND MAIN RESULTS: After 2 years, the mean dose of calcitriol in the treated group was 0.62 micrograms/d. Bone mineral density of the spine increased 1.94% with calcitriol therapy and decreased 3.92% with placebo (P = 0.001). Total body calcium increased 0.21% with calcitriol therapy and decreased 1.85% with placebo (P = 0.004). Patients receiving placebo had significant decreases in spine density (P = 0.0007) and total body calcium (P = 0.0004). There were no differences in vertebral fracture rates between the groups. Renal function studies were not statistically different between the groups after 2 years. CONCLUSION: The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium. No adverse effects on renal function were seen after long-term calcitriol therapy.

Aged↗

Evaluation of a continuous combined low-dose regimen of estrogen-progestin for treatment of the menopausal patient.

Menopause constitutes a sizable proportion of the adult women's life, and it is reasonable to consider that most women will benefit from hormone-replacement therapy. Also, it is important to realize that cardiovascular disease is a major cause of morbidity and death in the menopausal patient. Two regimens of hormone-replacement therapy were evaluated in postmenopausal women with 0.625 mg of conjugated equine estrogen with either 2.5 or 5 mg of medroxyprogesterone acetate taken continuously for 52 weeks in 92 patients. The data demonstrated an improvement in menopausal symptoms, a beneficial effect in lipoprotein profiles, the establishment of an atrophic endometrium, and a marked decrease in vaginal bleeding after 13 weeks and a further decrease after 26 weeks. Ideally this regimen will offer better patient compliance and, if the favorable lipoprotein profiles offer protection to the cardiovascular system, the overall health of the American woman will be markedly affected.

Cholesterol↗

Metabolic effects of synthetic calcitriol (Rocaltrol) in the treatment of postmenopausal osteoporosis.

The long-term safety and efficacy of synthetic 1,25-(OH)2D3 (calcitriol; Rocaltrol) in the treatment of women with type 1 osteoporosis is being assessed in a randomized trial. Patients were allocated in double-blind fashion to 1,25-(OH)2D3 or matching placebo. Initially, the calcium intake was adjusted to 1,000 mg/d. The study protocol called for increasing the dose of 1,25-(OH)2D3 until patients developed either hypercalcemia or hypercalciuria. However, in order to maintain a higher dose of calcitriol on a long-term basis, the calcium intake had to be reduced to 600 mg/d in those receiving calcitriol; if that was not successful in eliminating hypercalcemia and hypercalciuria, then the dose of 1,25-(OH)2D3 was reduced as necessary. During the hypercalcemic phase, the indices of bone resorption decreased significantly, demonstrating that calcium absorption is solely responsible for hypercalcemia. The maintenance dose was established after 8 to 10 weeks, and the 24-hour urine calcium and creatinine clearance remained constant throughout the remainder of the study period. On a calcium intake of 600 mg/d, the long-term maintenance dose of 1,25-(OH)2D3 averaged 0.675 micrograms/d. Long-term therapy on an average dose of 0.675 micrograms/d was not associated with nephrotoxicity.

Aged↗

Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate.

In postmenopausal osteoporotics, malabsorption of calcium is associated with reduced levels of serum 1,25-dihydroxyvitamin D. Metabolic studies have shown that calcium absorption can be normalized and calcium balance improved after administration of oral doses of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) 0.25 micrograms twice daily. Further studies performed at two centers compared the effect of Rocaltrol 0.25 micrograms twice daily versus placebo on vertebral fracture rates in osteoporotics. A significant reduction in vertebral fracture rates was seen at the end of 1 year. Those patients who continued on Rocaltrol for a second and third year showed a progressive decrease in vertebral fractures. Rocaltrol, administered at a dose of 0.25 micrograms twice daily, seldom causes hypercalcuria or hypercalcemia in osteoporotic patients on a typical calcium intake of 700 to 800 mg/d. Careful measurements of renal function over a period of 3 years in patients treated with Rocaltrol, 0.25 micrograms twice daily, showed no deterioration in renal function. These data suggest that 1,25-dihydroxyvitamin D3 is a useful therapy in the management of patients with postmenopausal osteoporosis, particularly those who have malabsorption of calcium. We found that it improves calcium balance, reduces the vertebral fracture rate, and is safe to use provided that the dietary calcium is monitored and does not exceed 800 mg/d.

Aged↗

The pathogenesis of osteoporosis.

Changes in the calciotropic hormones with age contribute significantly to the pathogenesis of osteoporosis. In both postmenopausal (Type I) and senile osteoporosis (Type II) it is common to find reduced levels of serum 1,25-dihydroxyvitamin D and malabsorption of calcium. In Type I patients a reduced level of serum parathyroid hormone causes a real decrease in serum 1,25-dihydroxyvitamin D production and malabsorption of calcium, whereas in Type II patients the decline in 1 alpha-hydroxylase activity in the kidney causes a decline in serum 1,25-dihydroxyvitamin D which leads to malabsorption of calcium and secondary hyperparathyroidism. In the final analysis both pathways lead to bone loss. In some Type II patients there may be a decline also in the function or number of the vitamin D-binding receptors in the gut. Treatment of patients with vitamin D analogues, however, normalizes calcium absorption and improves calcium balance. The improvement in calcium balance reduces bone resorption and prevents further bone loss; in addition recent studies have shown that therapy with vitamin D analogues leads to a reduction in fracture incidence.

Absorption↗

A comparison of iliac bone histomorphometric data in post-menopausal osteoporotic and normal subjects.

Transilial bone biopsies following in vivo fluorochrome labeling were obtained from 90 women with postmenopausal osteoporosis and 34 healthy post-menopausal women. Standard histomorphometric data were collected from undecalcified sections. The distribution of values for both structural and remodelling indices was the same for each group. Bone volume was 35% lower (P less than 0.001), wall thickness was 12% lower (P less than 0.001), and trabecular thickness was 11% lower (P less than 0.02) in osteoporotics. Trabecular separation was 34% greater (P less than 0.001) and trabecular number was 36% lower (P less than 0.001) in osteoporotics. Biopsy core width was 11% less (P less than 0.02) and cortical width was 35-50% less (P less than 0.001) in osteoporotics. Static indices of remodelling, mineralizing surfaces, and mineral apposition rate were similar in the two groups. The absolute values for bone histomorphometric variables for both groups are similar to most published data. Osteoporotics had poorer bone structure, marked by decreased trabecular connectivity and thin cortices. There were no major differences in dynamic indices of remodelling. Since the histomorphometric data were distributed the same in both groups, special subsets of osteoporotic subjects not in the normal population did not exist.

Aged↗

Lipid changes after hormone replacement therapy for menopause.

Three regimens of hormone replacement therapy were administered to 62 postmenopausal women for a period of 12 weeks and evaluated for their effect on blood lipids. Each group was given a continuous dose of 0.625 mg of conjugated estrogens combined with either a continuous dose of 2.5 mg of medroxyprogesterone acetate or 5.0 mg of medroxyprogesterone acetate, or a cyclic dose of 5.0 mg of medroxyprogesterone acetate on days 17-28 of the cycle. After treatment there was a significant decrease in the total cholesterol (P less than .0007) and low density lipoprotein cholesterol (P less than .0001) together with a significant increase in high density lipoprotein cholesterol (P less than .0029). There was no significant difference in the response of the blood lipids to the three hormone groups. Therefore, preference would depend on the combination that caused the least bleeding or amenorrhea.

Alanine Transaminase↗

Effect of estrone sulfate on postmenopausal bone loss.

Estrogen replacement therapy confers many beneficial effects to postmenopausal women, such as slowing the rate of bone loss and decreasing the risk of coronary artery disease. This multicenter, placebo-controlled study evaluated the lowest effective daily dose of estrone sulfate (0.3, 0.625, or 1.25 mg) combined with 1000 mg elemental calcium supplementation for preventing bone loss in the immediate supplementation for preventing bone loss in the immediate postmenopausal period. Spinal bone mineral density was measured using quantitative computed tomography. Compared with baseline, bone mineral density increased significantly (P less than .05) after 12 months of 0.625 mg daily (+ 1.9%) or 1.25 mg daily (+ 2.5%). The difference between the 0.625-mg and 1.25-mg doses was not statistically significant. Estrone sulfate administration (0.625 and 1.25 mg) produced significant changes in various lipid measurements at both the 6- and 12-month observation points. The prevalence rates for adverse events were comparable among the estrone sulfate groups and the placebo group. Estrone sulfate 0.625 mg daily, combined with 1000 mg elemental calcium supplementation, was the minimum effective dosage to prevent loss of spinal bone mineral density in postmenopausal women over a 12-month period.

Bone Density↗

Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride.

There has been controversy as to whether fluoride therapy increases the risk of fracture in the appendicular skeleton. In the present study we compared the incidence of hip fracture in four groups of osteoporotic women: 22 treated with placebo, 17 with fluoride and calcium, 18 treated with fluoride and calcitriol, and 21 with calcitriol alone. Four hip fractures occurred in 3 patients on fluoride and calcitriol, and two hip fractures occurred in 2 patients on fluoride and calcium. No hip fractures occurred in patients receiving either calcitriol alone or placebo. The difference in fracture rates for fluoride versus nonfluoride treatment is significant (p = 0.006). Moreover, the six hip fractures occurring in patients receiving fluoride during 72.3 patient years of treatment is 10 times higher than would be expected in normal women of the same age. The probability of observing six fractures in 2 years is extremely small (0.0003). In four of the hip fracture cases, the history suggested a spontaneous fracture. These findings suggest that fluoride treatment can increase the risk of hip fracture in osteoporotic women.

Aged↗

The effect of age and menopause on bone mineral density of the proximal femur.

Although the menopause has been associated with increased bone loss at several skeletal sites, it has not previously been noted in the hip, yet estrogen therapy has been reported to reduce the incidence of hip fractures. We investigated the effect of age and menopause on bone loss in the proximal femur by measuring bone mineral density (BMD) of the femoral neck, Ward's triangle, and trochanter by dual-photon absorptiometry in 263 normal women aged 20-84. Multiple regression analyses revealed a significant decrease in BMD of the femoral neck and Ward's triangle with age in both pre- and postmenopausal women (p less than 0.001). In the trochanter the decrease with age was significant only in postmenopausal women (p less than 0.001). Further analysis revealed that BMD decreased faster at all sites in the early postmenopausal years. During the first 6 years postmenopause, the decrease in BMD of the femoral neck and trochanter was 3-10 times higher than the change in the decade prior to menopause. About 20% of the lifetime femoral neck loss and 30% of the trochanteric loss occurred in the early postmenopausal period. It is concluded that both age and menopause are major determinants of BMD in the proximal femur. These findings could explain why estrogen therapy has been reported to prevent hip fracture. The rapid early postmenopausal loss in BMD of the proximal femur demonstrates the importance of starting estrogen replacement therapy immediately after menopause for maximum effect.

Adult↗

Change in vertebral shape in spinal osteoporosis.

The change in vertebral shape with increasing severity of spinal osteoporosis was studied in 139 women with atraumatic spinal fractures. The anterior height was below the normal range in 570 vertebrae, and the posterior height was below normal in 157 vertebrae. All values below the normal range were defined as fractures. Ninety-eight percent of posterior fractures were associated with anterior fractures. The fractures involved both the anterior and posterior vertebral borders in 58/356 (17%) of the fractured vertebrae in patients with 6 or less fractures, compared with 93/217 (45%) of the fractured vertebrae in patients with 7 or more fractures. The distribution of anterior fractures was biphasic with peak frequencies at T7-T8 and T11-T12. Posterior fractures had a more lumbar distribution, perhaps resulting from higher compressive forces on the posterior vertebral border of the lordotic lumbar spine than on the kyphotic thoracic spine. The mean anterior and posterior height of nonfractured vertebrae in osteoporotics was not significantly different from normal, suggesting that osteoporotics do not have smaller vertebrae than normal subjects.

Aged↗

Monitoring skeletal response to estrogen.

Estrogen replacement therapy at accepted doses is not fully effective in preventing bone loss and fractures in postmenopausal women. Bone densitometry is useful for monitoring estrogen replacement therapy to assess dose, foster compliance, and check for secondary bone loss. The most appropriate site for bone loss monitoring is probably the spine because it shows larger decreases at the menopause than appendicular sites, it shows larger increases with therapy, and it has clinical import in terms of fracture. Both dual-photon absorptiometry (or dual-energy x-ray absorptiometry) and computed tomography are the preferred monitoring methods. The precision of these densitometry methods is generally adequate to permit interim decisions with regard to continuing therapy, as well as conclusive decisions on therapeutic efficacy after 1 to 2 years of monitoring. Judicious use of densitometry in combination with biochemical determinations can enhance therapeutic control and provide both patient and physician confidence in long-term estrogen replacement therapy.

Absorptiometry, Photon↗

Estrogens in the prevention of osteoporosis in postmenopausal women.

Menopause-related bone loss leaves a woman at high risk for fractures. Estrogen use by postmenopausal women, especially when started within 3 years of the last menstrual period, prevents bone loss and reduces the risk of osteoporotic fractures. Estrogens do not restore lost bone. Withdrawal of estrogen therapy is followed by significant bone loss, thus suggesting that long-term therapy is needed. Concomitant progesterone therapy does not impair estrogen's bone-preserving activity.

Bone Diseases, Metabolic↗

Vertebral morphometry in diagnosis of spinal fractures.

Vertebral morphometry was performed on lateral thoracic and lumbar radiographs of 153 women with a preliminary diagnosis of spinal osteoporosis. Measurements included anterior and posterior vertebral height, width, area, wedge angle, percent reduction of anterior to posterior height (PRH) and percent difference in anterior height between adjoining vertebrae (PDAH). A vertebral fracture was identified if any of the measurements which control for interindividual variation in vertebral size (wedge angle, PRH, PDAH) were below the normal range. Among individuals with mild osteoporosis (0-2 fractures) PDAH identified 86% of the fractures and 95% of the individuals with fractures. Other measurements identified less than 71% of the fractures and less than 80% of the individuals with fractures. Although the results reflect a relative rather than a true sensitivity it appears that PDAH is the better diagnostic measurement for fractures in the earlier stages of spinal osteoporosis.

Aged↗