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Biomedical subjects

I R Reid

Publications and source records attributed to I R Reid.

At least 91 records · Page 5Linked to original sources
PubMed1996

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial.

PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.

Administration, Oral↗
PubMed1996

Accelerated bone loss in post-menopausal women with mild primary hyperparathyroidism.

OBJECTIVES: Osteopenia is regarded as an indication for parathyroidectomy in primary hyperparathyroidism. However, uncertainty exists as to the extent and degree of the skeletal effects in those with mild disease. We sought to determine whether mild primary hyperparathyroidism affects the rate of bone loss in postmenopausal women. DESIGN: Prospective 2-year comparison of rates of bone loss throughout the skeleton in 17 post-menopausal women with untreated mild asymptomatic primary hyperparathyroidism, and 48 age-matched, eucalcaemic controls. RESULTS: The women with primary hyperparathyroidism had a greater annual rate of loss of bone mineral density (BMD) of the total body (mean +/- SE, primary hyperparathyroidism -1.15 +/- 0.31%, controls -0.39 +/- 0.10%; P = 0.04) and its spine subregion (primary hyperparathyroidism -2.08 +/- 0.88%, controls 0.04 +/- 0.35%; P = 0.02). Lumbar spine BMD tended to decline in the primary hyperparathyroidism group (-0.35 +/- 0.33%) in contrast to the control group (+0.28 +/- 0.22%) (P = 0.10). There were no significant differences between the groups in rates of changes of BMD in the legs or the proximal femur. In the primary hyperparathyroidism group, the rate of total body bone loss in the eight women known at study entry to have had long-standing (> 5 years) primary hyperparathyroidism was -1.52 +/- 0.61%/year, similar to that of the whole group. CONCLUSION: Primary hyperparathyroidism is associated with an increased rate of loss of total body bone mineral density in post-menopausal women. Prolonged disease duration is therefore likely to be associated with an increasing risk of osteopenia, such that skeletal surveillance and interventions designed to reduce bone loss should be considered.

Aged↗
PubMed1996

Therapy of osteoporosis: calcium, vitamin D, and exercise.

Calcium supplementation has long been regarded as a fundamental part of the prevention and treatment of postmenopausal osteoporosis, but it is only in recent years that clear evidence has emerged demonstrating its impact on bone mass. Calcium supplementation does not completely arrest postmenopausal bone loss but slows the rate of decline by 30 to 50%. The effect of calcium supplementation on fracture incidence in postmenopausal women has not been established. Vitamin D deficiency is common in the frail elderly, particularly in countries where fortification or food with this vitamin is not practiced. Treatment of vitamin D deficiency has been associated with significant reductions in the number of hip fractures. The role of the potent vitamin D metabolites, calcitriol and alphacalcidol, in the management of postmenopausal osteoporosis is not clear. Although some studies show substantial benefits in bone density or fracture rate from the use of these compounds, the published data are inconsistent. In general, hormone replacement therapy and the potent bisphosphonates produce greater effects on bone density and there is a greater consistency among the results of the published studies of these other interventions. Controlled trials of exercise interventions in postmenopausal women show that exercise can positively influence bone density by a few percent. Exercise interventions in the elderly have been reported to decrease fall frequency by 10%. This latter effect may have a greater impact on fracture frequency than the modest benefits of exercise on bone-density.

Bone Density↗
PubMed1996

Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women.

Despite the widespread use of the C21 progestin medroxyprogesterone acetate (MPA) in hormone replacement therapy and gynecological practice, its effects on bone density are uncertain, with contradictory reports in the literature. We have examined the short term changes in bone density at the lumbar spine (a predominantly trabecular site) and the femoral neck (a predominantly cortical site) in 13 premanopausal women prescribed high dose MPA (50 mg/day) for gynecological disorders and in 12 control subjects. Compared to basal values, lumbar spine bone mineral density (measured by dual energy x-ray absorptiometry) fell progressively by a mean 2.4% at 6 months and 4.1% at 12 months (both P < 0.01); in five subjects who continued the drug, it had fallen by a mean 5.9% at 20 months (P < 0.002). The spinal bone loss in the MPA users was significantly greater than that in controls (P < 0.005 at 6 months; P < 0.01 at 12 months) and occurred despite a significant gain in body weight in the women using MPA (median, 3.5 kg at 6 months; P < 0.01). In four subjects in whom bone density was measured 6 months after cessation of MPA, spinal bone density showed significant recovery (mean increment, 2.8%; P < 0.025). Femoral neck bone density measurements did not differ between the groups. MPA induced amenorrhea in all subjects who continued with it beyond 6 months, and the amenorrheic subjects were estrogen deficient (median plasma estradiol, 70 pmol/L). We conclude that, when given in doses sufficient to induce hypogonadism, MPA use is associated with significant early loss of trabecular bone, which is probably the consequence of estrogen deficiency.

Administration, Oral↗
PubMed1995

Hip fracture incidence among older people in Auckland: a population-based study.

AIM: To determine the incidence of hip fractures among those aged 60 years or older in the Auckland region. METHODS: Demographic data were obtained on all older people hospitalised with a fracture of the femoral neck in Auckland, between 8 July 1991 and 7 February 1994. Incidence rates were calculated using the 1991 census data. RESULTS: An average incidence of 733 hip fractures or 710 individuals sustaining hip fractures each year was observed. Age-adjusted incidence rates were 571.5 per 100,000 for women and 318.2 per 100,000 for men. 97.0% of the hip fractures were sustained by those identified in the records as European, with the rates for Maori and Pacific Island populations 25-50% lower than for Europeans. Among Maori and Pacific Island populations, incidence rates were similar for men and women. Overall, 41.8% of the hip fractures were sustained by those > or = 85 years, with 67.0% sustained by those > or = 80 years. Incidence rates increased with age, with the rates continuing to increase in those > or = 85 years. CONCLUSION: Among Europeans, hip fracture incidence rates in Auckland are similar to those found for other caucasian populations. However, the rates among Maori and Pacific Island populations are among the lowest internationally and are similar for men and women. The increase in incidence rates with age continues in those > or = 85 years.

Aged↗
PubMed1995

Pamidronate treatment of the neurologic sequelae of pagetic spinal stenosis.

Spinal stenosis is a serious complication of Paget's disease of bone. Surgical decompression has a high complication rate and is not always effective. Medical therapy with bisphosphonates is established treatment in other forms of Paget's disease. To our knowledge, this is the first report of the use of intravenous pamidronate disodium as the sole treatment of lower limb weakness attributable to pagetic spinal stenosis. Our patient has been restored to independent living and has maintained his remission, with repeated treatment, for more than 5 years.

Aged↗
PubMed1995

Amylin stimulates osteoblast proliferation and increases mineralized bone volume in adult mice.

Amylin, a 37-amino-acid peptide co-secreted with insulin from the beta-cells of the pancreatic islets, has previously been demonstrated to inhibit bone resorption in vitro. However, its effects on bone formation and bone mass have not been assessed. We report that periphysiological concentrations of amylin stimulate proliferation of fetal rat osteoblasts in vitro. When amylin is injected daily for 5 days over the calvariae of adult mice in vivo, there are substantial increases in histomorphometric indices of bone formation, a reduction in bone resorption, and a significant increase in mineralized bone area. Equimolar doses of calcitonin in this in vivo model produced an inhibition of bone resorption but no significant effect on bone area. These findings support a role for amylin as a physiological regulator of bone and suggest that it should also be evaluated as a potential treatment for osteoporosis.

Amyloid↗
PubMed1995

Sources of interracial variation in bone mineral density.

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Ototoxicity associated with intravenous bisphosphonate administration.

The development of ototoxicity in association with intravenous pamidronate treatment of Paget's disease is described. The patient developed hearing loss, vertigo, and tinnitus which were exacerbated by subsequent infusions. This potentially serious drug side-effect does not appear to have been reported previously in patients with Paget's disease.

Diphosphonates↗
PubMed1995

An in vivo model for the rapid assessment of the local effects of parathyroid hormone on bone histomorphometry.

The process of bone remodelling is likely to be controlled to a large extent by factors acting locally in a paracrine or autocrine manner, along with some systemic control. In our laboratory we routinely use an in vivo model in which the local effects of factors on bone histomorphometry can be determined. The factor under investigation is injected just above the periosteum of the right hemicalvaria in the adult male mouse. These subcutaneous injections are given daily over a 1-week period and the animals sacrificed at intervals after the last injection. With appropriate staining techniques it is possible to determine the effects of a particular agent on osteoblast and osteoclast numbers; the area of total bone, mineralized bone, osteoid and periosteum; osteoblast, osteoclast and eroded surfaces, and thus to infer the rate of bone formation and bone resorption in the right hemicalvaria compared to the uninjected left hemicalvaria and to vehicle-injected control animals. All these parameters are measured using a bone-dedicated image analyzer. Utilizing this in vivo model, we and others have studied a number of bone-active factors. We report the effects of parathyroid hormone, as well as reviewing results of our studies of leukemia inhibitory factor, amylin, calcitonin and calcitonin gene-related peptide in the model. The results obtained are similar to those found in most other animal models and in man. In conclusion, we describe an in vivo model whereby bone-active factors, injected locally, can be rapidly assessed.

Animals↗
PubMed1995

The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women.

PURPOSE: To assess the effect of the antiestrogenic agent tamoxifen on bone mineral density in normal late postmenopausal women. METHODS: A randomized, double-blind, placebo-controlled trial was performed with 57 healthy, late postmenopausal women (mean 11 +/- 7 years since menopause). Subjects were assigned to take either tamoxifen 20 mg/d or placebo for 2 years. Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, trochanter) bone mineral densities were measured every 6 months using dual-energy x-ray absorptiometry. Serum and urine indices of bone turnover were measured at baseline, 6 months, and 2 years. RESULTS: In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 1.4%, while that in the women given placebo declined by 0.7% (P < 0.01 for difference between groups). Total body bone mineral density declined in both groups, but less so in the tamoxifen-treated women (P < 0.05). At both sites, the effect of tamoxifen was maximal after 1 year, with no further separation of the groups thereafter. There was no significant effect of tamoxifen on bone mineral density in the proximal femur. Tamoxifen produced significant falls in serum alkaline phosphatase (P < 0.0001), ionized calcium (P < 0.0001), and phosphate (P < 0.01), and in urinary excretion of hydroxyproline, n-telopeptides, and calcium (P < 0.05 for each). CONCLUSIONS: In normal late postmenopausal women, tamoxifen at a dose of 20 mg/d exerts a small protective effect on bone mineral density, comparable in magnitude to that of calcium supplementation and less than that of either estrogen or the bisphosphonates. Tamoxifen is unlikely to supersede any of these therapies in the management of postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1995

Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial.

PURPOSE: To determine the long-term effects of calcium supplements or placebo on bone density in healthy women at least 3 years postmenopause. PATIENTS AND METHODS: Eighty-six women from our previously reported 2-year study agreed to continue on their double-blind treatment allocation (1 g elemental calcium or placebo) for a further 2 years, with 78 women (40 on placebo) reaching the 4-year end point. Median (interquartile range) dietary calcium intakes for the whole group were 700 mg (range 540 to 910) per day at baseline, 670 mg (range 480 to 890) per day at 2 years, and 640 mg (range 460 to 880) per day at 4 years. The bone mineral density (BMD) of the total body, lumbar spine, and proximal femur was measured every 6 months by dual-energy, x-ray absorptiometry. RESULTS: There was a sustained reduction in the rate of loss of total body BMD in the calcium group throughout the 4-year study period (P = 0.002), and bone loss was significantly less in the calcium-treated subjects in years 2 through 4 also (difference between groups 0.25% +/- 0.11% per year, P = 0.02). In the lumbar spine, bone loss was reduced in the calcium group in year 1 (P = 0.004), but not subsequently. There was, however, a significant treatment effect at this site over the whole 4-year period (P = 0.03). In the proximal femur, the benefit from calcium treatment also tended to be greater in the first year and was significant over the 4-year study period in the femoral neck (P = 0.03) and the trochanter (P = 0.01). Nine symptomatic fractures occurred in 7 subjects in the placebo group and 2 fractures in 2 subjects receiving calcium (P = 0.037). CONCLUSIONS: Calcium supplementation produces a sustained reduction in the rate of loss of total body BMD in healthy postmenopausal women.

Absorptiometry, Photon↗
PubMed1995

The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women.

There is growing interest in the use of anti-estrogens as agents of disease prevention. Studies of women with breast cancer suggest that the synthetic anti-estrogen tamoxifen may reduce the incidence of cardiovascular disease, but the effects of this agent on cardiovascular risk factors in healthy women have not been studied. We have performed a two-year, randomized, placebo-controlled trial to assess the effects of tamoxifen 20 mg/day on serum lipids, fibrinogen, and body composition in 57 normal postmenopausal women. Tamoxifen treatment lowered levels of serum cholesterol by (mean +/- SE) 12 +/- 2%, low density lipoprotein cholesterol by 19 +/- 3%, and fibrinogen by 18 +/- 4% (P < 0.0001 vs. placebo for each). Levels of high density lipoprotein cholesterol were not altered by tamoxifen, but the ratio of total cholesterol to HDL-cholesterol decreased by 11 +/- 4% (P < 0.001 vs. placebo). Tamoxifen did not affect levels of triglycerides, high density lipoprotein cholesterol subfractions, apolipoprotein A1, or glucose, and did not change body weight, body mass index, or body fat distribution. We conclude that tamoxifen significantly reduces the levels of atherogenic lipids and fibrinogen in normal postmenopausal women. The results suggest that the anti-estrogens may substantially reduce the risk of cardiovascular disease, which remains the most common cause of death among postmenopausal women.

Adipose Tissue↗
PubMed1995

Regular exercise dissociates fat mass and bone density in premenopausal women.

Body weight is one of the principal determinants of bone density and fracture frequency, but there is significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight to this relationship. As previous studies have not considered the possible role of exercise in soft tissue-bone density interrelationships, we measured areal bone mineral density (BMD), fat mass, and lean mass in eumenorrheic premenopausal women and determined whether the interrelationships of these variables are influenced by the subject's exercise status. Subjects with mean activity levels of more than 140 kilojoules/kg.day (equivalent to undertaking vigorous physical activity for > 1.5 h/week) were classified as exercisers. In the nonexercising subjects (n = 36; age, 36 +/- 8 yr), BMD was markedly weight dependent (0.45 < r < 0.62), and this was contributed to by both fat and lean tissue. Because this finding may have arisen from the mutual dependence of soft tissue mass and areal BMD on body size, fat and lean masses were reexpressed as a percentage of body weight. The percent fat tended to be positively related to areal BMD (0.23 < r < 0.35), whereas the percent lean was inversely related to this index. A second way of obviating the mutual dependence of soft tissue mass and areal BMD on body size is to derive BMD/height as an index of volumetric bone density. This parameter was only related to lean mass in the femur, whereas the correlations with fat mass were little changed. The percent fat was positively (0.29 < r < 0.43) and the percent lean was negatively (-0.43 < r < -0.29) related to BMD/height throughout the skeleton, including the femur. In the exercising subjects (n = 63; age, 33 +/- 8 yr), fat mass and lean mass were unrelated to BMD/height (r < 0.23). However, the percent lean was positively correlated with BMD and BMD/height in the femoral neck (r = 0.28 and r = 0.31, respectively). It is concluded that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, possibly through the effects of weight-bearing exercise on both of these variables.

Adipose Tissue↗
PubMed1994

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism.

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.

Adipose Tissue↗