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Biomedical subjects

J Eisman

Publications and source records attributed to J Eisman.

At least 19 recordsLinked to original sources
PubMed2004

A meta-analysis of previous fracture and subsequent fracture risk.

Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Adolescent↗
PubMed2001

ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men.

A number of previous investigations showed significant associations between polymorphisms of the vitamin D receptor (VDR) gene and bone mineral density (BMD). BMD is influenced by hormones and the rate of skeletal remodeling. A study was performed to investigate the possible relationship between Apa I, Bsm I, Taq I, and Fok I polymorphisms of the VDR gene and serum 1,25-dihydroxyvitamin D (1,25[OH]2D), osteocalcin, and propeptide of type I collagen (PICP)-markers of bone turnover, total body calcium, and BMD of the total body, radius, lumbar spine, trochanter, and femoral neck-in 39 young adult black men of 20 to 40 years of age and 44 age-, height-, and weight-matched white men. The distribution of each of the four alleles of the VDR genotypes was similar in the two racial groups. The Apa I VDR genotype was associated with serum PICP (P =.0494) but not with serum 1,25(OH)2D or serum osteocalcin. A significant association between the Apa I VDR genotype and BMD of the lumbar spine (P =.0291) was also observed. However, the Bsm I, Taq I, and Fok I genotypes were not significantly associated with BMD or serum osteocalcin, PICP, or 1,25(OH)2D. Multivariate stepwise analysis indicated that (1) the Apa I VDR genotype was associated with BMD of the lumbar spine in the two groups together; with total body calcium and BMD of the total body, radius, trochanter, and femoral neck in the black men; and with BMD of the radius in the white men; analysis also indicated that (2) race was significantly associated with total body calcium and BMD of the total body, lumbar spine, and femoral neck. In summary, the Apa I VDR genotype is associated with serum PICP and BMD at a number of sites but does not contribute to or account for racial differences in BMD in young adult men.

Adult↗
PubMed2001

Protective effect of short-tem calcitriol or cyclical etidronate on bone loss after cardiac or lung transplantation.

Bone loss is most rapid in the immediate period after cardiac or lung transplantation. This randomized study compared the efficacy of 6 months of treatment with either calcitriol (1,25-dihydroxyvitamin D3; 0.5 microg/day) or two cycles of etidronate plus calcium in preventing bone loss in 41 patients undergoing cardiac or lung transplantation. Patients were followed for 18 months after cessation of treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). There were no significant differences between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporin over the 2 years. Bone loss did not differ between groups after 6 months and, despite 6 months prophylaxis with either agent, bone loss was significant in both groups at 6 months and 12 months. However, compared with an untreated reference group, both therapies offered significant protection at 6 months and etidronate provided significant protective carryover after therapy had been discontinued. These data suggest short-term prophylaxis with calcitriol or cyclical etidronate is partially effective in reducing bone loss after cardiac or lung transplantation but treatment needs to be continued for a longer term.

Adrenal Cortex Hormones↗
PubMed2000

Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use.

BACKGROUND: Few data are available regarding vertebral fracture risk in patients treated with oral corticosteroids. The aim of this study was to determine the prevalence and the role of risk factors such as age, bone mineral density (BMD), and corticosteroid use for vertebral deformity in patients receiving long-term corticosteroid therapy. METHODS: Thoracolumbar x-ray films, BMD, and details on corticosteroid use were obtained on 229 consecutive patients treated with long-term corticosteroid regimens (> or = 6 months of prednisone, > or = 5mg/d or equivalent) seen at 4 referral centers. Comparisons were made with a population control group of 286 male and female controls not taking corticosteroids (aged > or = 60 years). RESULTS: Sixty-five patients (28%) had at least 1 vertebral deformity and 25 (11%) had 2 or more vertebral deformities. Older age, independent of BMD, was a significant risk factor for deformity. Patients aged 70 to 79 years had a 5-fold increased risk of deformity compared with patients younger than 60 years (odds ratio, 5.13; 95% confidence interval, 2.03-13.0). Compared with the population controls, the prevalence of deformities increased to a greater extent with each decade of age in the corticosteroid group (P =.005). Mean lumbar spine and femoral neck BMD Z scores were lower in the steroid-treated patients with deformities compared with the nonsteroid control group with deformities. When the effects of age, sex, body mass index, and duration of corticosteroid use were adjusted for in logistic regression analysis, low BMD was a modest predictor of deformity (for a 1-SD decrease in lumbar spine BMD: odds ratio, 1.31; 95% confidence interval, 1.02-1.68) and for a 1-SD decrease in femoral neck BMD: odds ratio, 1.77; 95% confidence interval, 1.07-2.94). CONCLUSIONS: The combination of increasing age and corticosteroid use is associated with a marked increase in the risk of vertebral deformity. Elderly patients commencing long-term corticosteroid therapy should be considered for antiosteoporotic therapy independently of their BMD. Arch Intern Med. 2000;160:2917-2922

Age Factors↗
PubMed2000

Effect of calcitriol on bone loss after cardiac or lung transplantation.

Rapid bone loss after cardiac and lung transplantation results in an increased risk of osteoporotic fracture. This study examined the efficacy of treatment with calcitriol (1,25-dihydroxyvitamin D3) in preventing bone loss in patients undergoing cardiac or lung transplantation. In this 2-year double-blind, stratified study, 65 patients undergoing cardiac or single lung transplantation were randomly allocated to receive either placebo or calcitriol (0.5-0.75 microg/day), the latter for either 12 months or 24 months. All patients received 600 mg calcium/day. Bone mineral density (BMD) was measured every 6 months for 2 years by dual-energy X-ray absorptiometry. There was no significant difference between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporine over the 2 years. Bone loss at the proximal femur was significantly reduced or prevented at all three sites by treatment with calcitriol for 2 years compared with treatment with calcium alone. Treatment with calcitriol for 12 months followed by calcium for 12 months resulted in similar proximal femoral bone loss to that seen in those patients treated with calcium for 24 months, suggesting calcitriol prophylaxis needs to be continued beyond 12 months. At the lumbar spine, there were no significant differences in BMD between groups. Over a period of 2 years, 22 new vertebral fractures/deformities occurred in 4 patients treated with calcium alone compared with one new vertebral fracture in 1 patient treated with calcitriol. Because the sample size was too low to provide reliable interpretation of vertebral fracture rates, this difference is likely a chance result. Mild hypercalcemia was common with calcitriol therapy, as was mild hypercalciuria (59% of patients vs. 10% controls), but there were no significant differences between groups in serum creatinine after 2 years. These data suggest calcitriol has a role in reducing proximal femur bone loss after cardiac or lung transplantation but treatment needs to be continued beyond 1 year.

Adrenal Cortex Hormones↗
PubMed1998

Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group.

BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for preventing postmenopausal bone loss. DESIGN: 3-year double-blind, randomized, placebo-controlled trial. SETTING: 15 osteoporosis centers throughout the world. PARTICIPANTS: 447 women who had recently experienced menopause (6 to 36 months before study entry). INTERVENTION: Participants were randomly assigned to one of five regimens: oral placebo; oral alendronate, 1, 5, or 10 mg/d; or oral alendronate, 20 mg/d for 2 years followed by placebo during the third year (20/0 mg/d). MEASUREMENTS: Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover and bone quality were assessed with biochemical markers and bone histomorphometry. RESULTS: Alendronate at 5, 10, and 20/0 mg/d increased bone mineral density from baseline at the lumbar spine, femoral neck, and trochanter by 1% to 4% and in the total body by 0.3% to 1.0%; placebo led to losses of 2% to 4% at these sites. Alendronate, 1 mg/d, attenuated losses relative to those seen with placebo. Alendronate decreased markers of bone resorption to a new steady state by 3 months and decreased markers of bone formation by 6 to 12 months. Bone quality remained normal. At all dosages studied, alendronate had a safety and tolerability profile similar to that of placebo. CONCLUSIONS: In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.

Adult↗
PubMed1998

Tissue specific and vitamin D responsive gene expression in bone.

Studies of gene expression in bone have adopted a number of molecular approaches that seek to determine those cis and trans-acting factors responsible for the development and physiological regulation of this unique tissue. The majority of studies have been performed in vitro, focussing on the expression of genes such as osteocalcin, bone sialoprotein and type I collagen which demonstrate restricted or altered expression patterns in osteoblasts. These studies have demonstrated a large number of cis and trans acting factors that modulate the tissue specific and vitamin D responsive expression of these genes. These include the response elements and regions mediating basal and vitamin D dependent transcription of these genes as well as some of the transcription factors that bind to these regions and the nucleosomal organisation of these genes within a nuclear framework. In vivo studies, including the introduction of transgenes into transgenic mice, extend these in vitro observations within a physiological context. However, in part due to limitations in each approach, these in vitro and in vivo studies are yet to accurately define all the necessary cis and trans-acting factors required for tissue specific and vitamin D responsive gene expression. Advances have been made in identifying many cis-acting regions within the flanking regions of these genes that are responsible for their restricted expression patterns, but a vector incorporating all the necessary cis-acting regions capable of directing gene expression independent of integration site has not yet been described. Similarly, trans-acting factors that determine the developmental destiny of osteoblast progenitors and the restricted expression of these genes remain elusive and, despite advances in the understanding of protein-DNA interactions at vitamin D response elements contained within these genes, further intermediary factors that interact with the transcriptional machinery to modulate vitamin D responsiveness need to be identified.

Animals↗
PubMed1998

Allelic variation in the vitamin D receptor, lifestyle factors and lumbar spinal degenerative disease.

OBJECTIVE: To describe the relation between spinal degenerative disease, allelic variation in the vitamin D receptor gene, and lifestyle factors in a population-based association study. METHODS: Random population-based sample of 110 men and 172 women over 60 years of age participating in the Dubbo Osteoporosis Epidemiology Study who had spinal radiographs (performed according to a standardised approach), assessment of lifestyle factors, bone densitometry as well as blood taken for genotyping. RESULTS: Spinal degenerative disease of varying severity was common in this sample. Multivariate analysis of genetic and lifestyle factors simultaneously strengthened the statistical significance of each indicating the presence of additive gene environment interaction. Allelic variation in the vitamin D receptor gene was associated with severity of osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59). Adjustment for femoral neck bone density did not change these findings suggesting that the association is not mediated through bone density. Presence and severity of spinal degenerative disease increased with age at all sites. Current smoking increased both the presence (adjusted OR 9.70, 95% CI 2.08, 45.1) and severity (adjusted OR 2.91, 95% CI 1.16, 9.03) of spinal osteophytosis with intermediate values for past smokers. Severity of osteophytosis was also independently associated with body mass index and quadriceps strength consistent with a contributory effect of physical loading. CONCLUSIONS: In this elderly sample, both genetic and lifestyle factors were associated with the presence and severity of spinal degenerative disease. There were site specific differences in associations at the spine, which may be because of misclassification of disease status or may indicate possible environmental and genetic differences in the pathophysiology of spinal degenerative disease. Further studies are required to confirm these findings in different population samples and to further explore potential aetiological mechanisms particularly gene environment interaction.

Aged↗
PubMed1998

Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA. METHODS: We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted "tt", and absence "TT". RESULTS: In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics. CONCLUSION: The presence of the VDR gene "t" allele in female patients with RA was associated with accelerated bone loss.

Alleles↗
PubMed1997

The epidemiology and pathogenesis of osteoporosis.

Osteoporosis is an increasing health care concern as populations age throughout the developed and developing world. The social and economic costs of osteoporosis are due to its clinical outcome of fracture which increases exponentially with age. This review will highlight some of the key epidemiological aspects of osteoporosis incorporating areas of more recent interest. These include the definition; the magnitude of the problem encompassing differing incidence and prevalence patterns of both low bone mass and fracture in different cultural groups; the social consequences of fracture, including economic costs, morbidity and mortality; the evaluation of fracture risk, including the role of bone density, bone quality and the risk of falling; as well as an overview of some of the factors involved in determining low bone mass. Bone mineral density (BMD) is the most easily measured and accurate predictor of fracture risk. For any individual, BMD is the combination of their peak bone density and subsequent bone loss, both of which are influenced by genetic, hormonal and environmental factors. An understanding of key issues relating to this important disease may lead to earlier detection of the individual at high risk for fracture and rational approach to prevention and management.

Age Distribution↗
PubMed1995

Identification and characterisation of a novel human RNA-binding protein.

The processing of heterogeneous nuclear RNA (hnRNA) into a mature message occurs within a number of different nuclear ribonucleoprotein (RNP) complexes which bind to the hnRNA and provide the machinery for these modifying events. Although some components of the nuclear RNP complexes have been isolated, many remain to be elucidated. We report here the isolation of a novel human nucleic-acid-binding protein isolated by screening a lambda gt11 expression library with an oligodeoxyribonucleotide probe. The complete cDNA clone (E5.1) is homologous to a recently published murine sequence. The human gene encodes a ubiquitously expressed mRNA sequence with a putative open reading frame of 305 amino acids and contains a number of domains found in well characterised RNA-binding proteins. The E5.1-derived RNA recognition motif (RRM) is phylogenetically most related to the hnRNP C protein, a component of heterogeneous nuclear RNP particles which participates in mRNA splicing in vitro. E5.1 may, therefore, represent a novel gene, encoding a protein involved in processing of precursor RNAs into mature mRNA.

Amino Acid Sequence↗
PubMed1995

The osteocalcin and collagen type I (alpha 1) promoters share common basal regulatory units.

Sequential activation of osteoblast-specific genes occurs during cell development. Regulation of these genes is through the cooperation between basal, hormone-responsive, and growth factor-responsive transcriptional control elements. The active hormone, 1,25-dihydroxyvitamin D3 plays an important role in the regulation of osteocalcin and other osteoblast-expressed genes. As well as containing a vitamin D response element, the upstream region of the osteocalcin promoter also has potent basal activity in the osteoblast-like ROS17/2.8 cell line. The present study identifies a short DNA sequence that contributes to basal promoter activity. This osteocalcin cis-acting response element (OSCARE-1) has two basal regulatory elements: a G/C-rich element and an adjacent reverse CCAAT element. Homologous sequences have been characterized as negative and positive basal regulatory elements, respectively, in the promoter of the collagen type I (alpha 1) gene. In electrophoretic mobility-shift assays, this collagen regulatory unit and OSCARE-1 produce similar banding patterns and bind common ROS17/2.8 nuclear proteins. Mutations of the G/C element in the collagen promoter showed that it functions as an inhibitory element in NIH-3T3 cells. Introduction of the same mutations into the G/C element of the OSCARE-1 unit exposed a similar repressive activity in NIH-3T3 cells, which correlated with an altered electrophoretic mobility-shift assay banding pattern. We have shown a similarity between a basal regulatory unit in the distal osteocalcin promoter and a unit in the proximal collagen type I (alpha 1) promoter. The fact that similar units are present in other osteoblast-specific promoters suggests that OSCARE-1-like units may be a common regulator of osteoblast-expressed genes.

3T3 Cells↗
PubMed1995

Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women.

Common vitamin D receptor (VDR) gene alleles have recently been shown to contribute to the genetic variability in bone mass and bone turnover, however, the physiological mechanisms involved are unknown. To examine this, the response to 7 days of 2 micrograms oral 1,25-dihydroxyvitamin D[1,25-(OH)2D] (calcitriol) stimulation was assessed in 21 premenopausal women, homozygous for one or other of the common VDR alleles (bb, n = 11; BB, n = 10). Indices of bone turnover and calcium homeostasis were measured during 2 weeks. Baseline osteocalcin, 1,25-(OH)2D, type I collagen carboxyterminal telopeptide, and inorganic phosphate levels were significantly higher and spinal bone mineral density was significantly lower in the BB allelic group. After calcitriol administration, similar levels of 1,25-(OH)2D were attained throughout the study in both genotypic groups. The increase in serum osteocalcin levels in the BB group was significantly less than that in the bb group (11% vs. 32%, P = 0.01). The genotype-related baseline difference in osteocalcin levels was not apparent at the similar serum 1,25-(OH)2D levels. By contrast, the baseline differences in phosphate and type I collagen carboxyterminal telopeptide persisted throughout the study. Serum ionized calcium levels did not differ between genotypes, nor did it move out of normal range values. However, parathyroid hormone was less suppressed in the low bone density group (38% vs. 11%, P = 0.01). These data indicate that the VDR alleles are associated with differences in the vitamin D endocrine system and may have important implications in relation to the pathophysiology of osteoporosis.

Adult↗