Biomedical subjects

N H Bjarnason

Publications and source records attributed to N H Bjarnason.

28 records · Page 2Linked to original sources

PubMed1999

Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group.

Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p </= 0.004). Women with a lower percentage of body fat or BMI had higher baseline levels of urine N-telopeptide cross-links (r = -0.24 to -0.31, p < 0.0001) and serum osteocalcin (r = -0.12 to -0.15, p < 0.01). To determine if the magnitude of treatment effect of alendronate was dependent on these risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women.

Alendronate↗

PubMed1998

Postmenopausal bone remodelling and hormone replacement.

Osteoporosis is a serious, frequently occurring disease. Sensitive, specific and precise biochemical measures of bone remodelling, thus, are important tools in the evaluation of bone loss, fracture risk and treatment response. Bone turnover is predictive of the subsequent rate of loss. A high bone turnover documented by increased levels of biochemical markers predicts an increased rate of loss in bone mass. Additionally, as a high bone turnover leads to an increase in the extent of bone resorption as well as an increase of the erosion depth, this may also cause deterioration of the bone structure, thereby leading to an increased risk of fracture. That the predictive values of bone mass and markers of bone turnover are additive suggests that these measures describe different properties of bone. Hormone replacement induces a reduction in postmenopausal bone turnover, arrests loss of bone mass and decreases fracture risk. The skeletal response to therapy is reflected by bone markers and these may be used for monitoring purposes. Those who are in most need of treatment can be identified by a combination of bone mass and bone marker measurement. Furthermore, those who need the treatment most will demonstrate the best response in terms of bone mass. Concern has arisen because of a relatively large day-to-day variation, especially in urinary markers; however, this seems to be resolved through use of the new serum markers.

Bone Remodeling↗

PubMed1998

Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides.

The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum CrossLaps assay for monitoring antiresorptive therapy in osteoporosis treatment. Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy. The corresponding urine samples were measured in the urine CrossLaps ELISA and corrected for creatinine excretion. The serum CrossLaps measurements and corresponding urinary CrossLaps measurements were highly correlated (r >0.8 for all studies). The serum and urine CrossLaps measurements showed a significant decrease among the women treated with clinically relevant doses of either of the antiresorptive agents. Furthermore, the annual percentage change in bone mineral density (BMD) correlated with the measured changes in CrossLaps concentration. The serum CrossLaps assay showed a specificity of 83-100% and a sensitivity of 59-83% for assessing BMD changes. The corresponding values for the creatinine-corrected urinary measurements were 83-92% specificity and 68-79% sensitivity. We conclude that performance of the convenient Serum CrossLaps One Step ELISA is at least equivalent to that of the urine text for follow up of antiresorptive treatment in osteoporosis. Further studies are needed to optimize its use in this and other clinical applications.

Aged↗

PubMed1997

Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.

BACKGROUND: Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues. METHODS: We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months. RESULTS: The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (+/-SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4+/-0.4 percent for the lumbar spine, 2.4+/-0.4 percent for the total hip, and 2.0+/-0.4 percent for the total body (P<0.001 for all comparisons). Serum concentrations of total cholesterol and low-density lipoprotein cholesterol decreased in all the raloxifene groups, whereas serum concentrations of high-density lipoprotein cholesterol and triglycerides did not change. Endometrial thickness was similar in the raloxifene and placebo groups at all times during the study. The proportion of women receiving raloxifene who reported hot flashes or vaginal bleeding was not different from that of the women receiving placebo. CONCLUSIONS: Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.

Bone Density↗

PubMed1997

Raloxifene inhibits aortic accumulation of cholesterol in ovariectomized, cholesterol-fed rabbits.

BACKGROUND: The beneficial effect of long-term hormone replacement therapy in terms of a decreased risk of cardiovascular disease is now generally accepted. Raloxifene, a selective estrogen receptor modulator, has demonstrated hypolipidemic properties while leaving the endometrium unstimulated. METHODS AND RESULTS: For our study of the effects of raloxifene on atherosclerosis, 75 rabbits were ovariectomized and treated with either raloxifene, 17beta-estradiol, or placebo; 25 rabbits were sham operated and treated with placebo. After 45 weeks, the raloxifene group had two thirds of the aortic atherosclerosis, as evaluated by the cholesterol content of the proximal inner part of the aorta, found in the placebo group (placebo, 577+/-55.1 nmol/mg protein; raloxifene, 397+/-53.6 nmol/mg protein; P<.05); the estrogen group had one third of the aortic atherosclerosis in the placebo group (estrogen, 177+/-32.1 nmol/mg protein; P<.001). The sham-operated group (473+/-59.6 nmol/mg protein) was not significantly different from placebo. These effects were only partly explained by the changes in serum lipids and lipoproteins, and treatment with both estrogen and raloxifene independently predicted the response in aorta cholesterol. Because plasma levels of total raloxifene were low relative to clinical values in postmenopausal women, dose-response data for raloxifene are required. CONCLUSIONS: Our findings indicate that raloxifene hydrochloride has a potentially important antiatherogenic effect, analogous to that observed with estrogen in this model.

Animals↗

PubMed1997

The response in spinal bone mass to tibolone treatment is related to bone turnover in elderly women.

To determine the ability of bone turnover to predict the response in bone mass during treatment with Tibolone, two biochemical markers of bone metabolism were evaluated [CrossLaps corrected for urinary creatinine (CrossLaps/Cr.) and serum osteocalcin measured in a newly developed assay (N-Mid)]. Data from a 2-year double-blind, randomized trial with 56 completing Tibolone-treated women and 13 placebo-treated women were studied. Bone mineral density in the spine (QDR-1000) and indices of bone turnover were determined every 3 months throughout the study. The response in bone mass was calculated as the percent annual change in bone mineral density from baseline and was determined from a total of nine measurements. The response in bone mass was correlated to prestudy values of CrossLaps/Cr. (r = 0.27; p < 0.05), but was uncorrelated to prestudy values of N-Mid. The changes from baseline of these two markers were significantly correlated with the response in bone mass from the 6 months' time point and throughout the rest of the study, i.e., at 1 year: CrossLaps/Cr.: r = 0.54; p < 0.001, N-Mid: r = 0.49; p < 0.001). The change from baseline in the two markers was clearly more predictive of the response in bone mass than the baseline values of these markers as evaluated in a multiple, linear regression-model. Within 1 year of Tibolone-treatment, measured changes in CrossLaps/Cr. and bone mineral density are at least equally predictive of the true response in bone mass over 2 years. These results indicate a possibility of monitoring Tibolone therapy with biochemical markers of bone turnover, at least on group basis.

Aged↗

PubMed1997

Tibolone: influence on markers of cardiovascular disease.

Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss. The influence of tibolone treatment on coagulation, fibrinolysis, and lipid metabolism was investigated in 91 healthy late postmenopausal women. They were randomly assigned in a double-blind, placebo-controlled 2-year study to receive either tibolone 1.25 mg (n = 36, 29 completed) or 2.5 mg (n = 35, 28 completed) or placebo (n = 20, 13 completed). The biochemical markers of lipid metabolism, fibrinolysis, and coagulation were measured every 3 months. In both tibolone groups a similar (approximately 30%) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 (P < 0.001) was detected. Also serum total cholesterol and triglycerides were reduced (approximately 15%; P < 0.01), whereas low density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were unaffected by tibolone. The two dose levels of tibolone resulted in a similar, marked lowering (approximately 30%) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo (P < 0.001). Plasminogen increased (approximately 15%; P < 0.001) in both groups. Fibrinogen was lowered (P < 0.01) in the low-dose group, and antithrombin III remained unchanged. The overall effect on hemostatic factors of the present doses of tibolone in healthy, late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation. This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol.

Aged↗

PubMed1996

Tibolone: prevention of bone loss in late postmenopausal women.

The aim of the study was to assess the effects of 2 yr of treatment with two dose levels of tibolone on bone mineral density and bio-chemical markers of bone metabolism in late postmenopause. Ninety-one healthy women, more than 10 yr after menopause, entered a 2-yr double blind, randomized, placebo-controlled study of treatment with either 1.25 mg/day (n = 36) or 2.5 mg/day (n = 35) Tibolone or placebo (n = 20). Densitometry and determinations of biochemical markers of bone metabolism in serum and urine were performed before randomization and every 3 months during the study. The results revealed a steady and equal increase in bone mineral density in both tibolone groups at the bone sites studied. Gains in BMD spine of 5.9 +/- 0.9% in the 1.25 mg group, 5.1 +/- 0.9% in the 2.5 mg group, and 0.4 +/- 1.1% in the placebo group were found. In the forearm, increases of 2.2 +/- 0.7% in the 1.25 mg group and 1.9 +/- 1.1% in the 2.5 mg group were detected, whereas the placebo group lost 2.1 +/- 1.0%. This was fully supported by changes in biochemical markers of bone resorption (urinary excretion of fragments from the osteoclastic degradation of the alpha 1-chain of the C telopeptides of type 1 collagen and hydroxyproline) and bone formation (serum osteocalcin), respectively. In conclusion, within 2 yr of treatment, tibolone increases bone mass in the spine and prevents bone loss in the forearm in late postmenopausal women determined by densitometry and several biochemical parameters of bone turnover. Tibolone at two doses (1.25 and 2.5 mg/day) had similar effects, indicating that even lower doses may be efficacious.

Aged↗

PubMedDate not supplied

Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials.

BACKGROUND: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women. METHODS: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. RESULTS: Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). CONCLUSIONS: Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.

Bone Density↗

PubMedDate not supplied

Evidence that increased calcium intake does not prevent early postmenopausal bone loss.

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (+/- SE) BMD decreased by 1.9% +/- 0.16% at the lumbar spine and 1.6% +/- 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869-1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.

Bone Density↗