Relationship of common allelic variation at the vitamin D receptor locus to bone mineral density and bone turnover.
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Alleles↗
Biomedical subjects
C Christiansen
Publications and source records attributed to C Christiansen.
Evaluation of a new commercial IRMA for bone-specific alkaline phosphatase during treatment with hormone replacement therapy and calcitonin.
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Alkaline Phosphatase↗
Coated-tube radioimmunoassay for C-telopeptides of type I collagen to assess bone resorption.
We present a coated-tube RIA that is useful for assessment of bone resorption. The assay uses a monoclonal antibody raised against a linear 8-amino-acid sequence (EKAHDGGR) derived from the C-telopeptides of type I collagen. Within-run and total CVs were 4.4% and 5.3-6.2%, respectively, at concentrations of 1-7 mg/L (n = 4-20). Analytical recovery was 98% +/- 8% and dilution 97% +/- 7%. Values obtained in a group of 36 premenopausal women were 227 +/- 89.6 mg/mol creatinine. In a group of 141 postmenopausal women, the values obtained were 429 +/- 225 mg/mol creatinine, a highly significant increase of 89% (P <0.001) over the premenopausal value. In a double-blind placebo-controlled clinical study of these postmenopausal women receiving five different doses of a bisphosphonate, a significant decrease of RIA-measured C-telopeptide values was seen in all bisphosphonate-treated groups, after just 3 months. Values in urine samples from postmenopausal women assayed with the RIA (gamma) and the CrossLaps(TM) ELISA (x) agreed well: slope = 0.98 (95% confidence interval, 0.94-1.01), intercept = 0.34 (0.25-0.43) mg/L, and Sylx = 0.93 mg/L (n = 678). We conclude that this RIA represents a valuable tool for assessing bone resorption.
Adult↗
Structure and organization of albumin molecules forming the shell of air-filled microspheres: evidence for a monolayer of albumin molecules of multiple orientations stabilizing the enclosed air.
The structure and organization of albumin molecules in the shell of air-filled microspheres formed by sonication of a 5% albumin solution have been investigated. By limited proteolysis of intact microspheres, it has been shown that every albumin molecule in the shell may be cleaved without disintegration of the microsphere structure. The microsphere shell accordingly appears to be composed of a monolayer of albumin molecules. Most of the main cleavage sites identified after N-terminal sequencing of proteolytic fragments are localized in three distinct regions common to both native and microsphere albumin molecules: the extended region of the first domain, the extended region of the second domain and the first disulphide loop of the third domain. The similarity in the localization of cleavage sites in the native and microsphere albumin molecules suggests that the formation of microspheres implies only a limited degree of conformational change of the albumin molecules. The localization of the cleavage sites in the three-dimensional structure of albumin suggests that the shell may be constituted of albumin molecules in both a native-like heart-shaped form and a more flipped-out elongated form with different orientations.
Air↗
Cost-effectiveness of fracture prevention in established osteoporosis.
This study presents the results of a computer simulation model for calculating the cost-effectiveness and cost-utility of treating patients with established osteoporosis in order to reduce the risk of fractures. The results are based on Swedish data for risk of fracture and costs. The treatment intervention modelled is based on treatment of a 62-year-old woman with established osteoporosis. The cost per hip fracture avoided is 350,000 SEK, assuming a 50% reduction in the risk of fracture due to 5 years of treatment. A sensitivity analysis for changes in the cost and effectiveness of treatment, the risk of fracture and the discount rate is performed. The cost per life-year gained and the cost per quality-adjusted life-year (QALY) gained is presented to enable comparison of the cost-effectiveness of treating osteoporosis with that of other health care interventions. A comparison between treating the same woman for osteoporosis and mild hypertension shows a cost per life-year gained of 220,000 SEK and 128,000 SEK respectively. Cost per QALY gained is very similar for the two interventions: 105,000 SEK and 103,000 SEK respectively. This model provides a tool to enable clinicians, administrators and health policy makers to analyze and understand the economic aspects of a major health policy issue.
Computer Simulation↗
What should be done at the time of menopause?
Peak bone mass and aggregate bone loss each contribute to low bone mass found later in life, and obviously the contribution of bone loss will increase as people age. Menopause is the time where bone loss begins to accelerate from the existing peak bone mass. It thus seems obvious that, in order to stratify the female population into groups at various risk, bone mass and rate of loss are the parameters to determine. Which site to measure for the most effective risk assessment has not been determined. All sites seem to give a relatively similar assessment of risk for all subsequent fractures. If the measurement is > 1 standard deviation (SD) above the mean for young normals, no further measurement would be needed and no intervention undertaken. If the measurement is < 1 SD below the mean for young normals, intervention would be recommended (provided no contraindications were present). For those within +/- 1 SD, the rate of loss should be determined. Some individuals lose bone at a more rapid rate than others, and this rapid rate may persist in some of these individuals over a period of years. Studies have shown that women that were classified to be fast losers at menopause have lost approximately 50% more bone mass, at the wrist, spine, and hip within 12 years after menopause than those diagnosed as normal bone losers. The rate of bone loss in postmenopausal women may be indirectly assessed by use of a number of biochemical markers. Fast losers have elevated concentrations of these markers compared with slow bone losers. The risk of developing osteoporosis later in life is thereby determined by combining the values for the present measured bone mass and the magnitude of the estimated future bone loss.
Biomarkers↗
Spontaneous postmenopausal bone loss in different skeletal areas--followed up for 15 years.
We examined the spontaneous bone loss in two populations of healthy postmenopausal women, who were followed for 9.5 and 14.5 years without any treatment influencing the calcium metabolism. The bone mass was measured in different skeletal areas: the distal forearm, the lumbar spine, the proximal femur, and the total skeleton. The spontaneous bone loss in the distal forearm, the lumbar spine, and the total skeleton was fitted to an exponential model as a function of years since menopause. The overall bone loss averaged 20-25% of premenopausal bone mass 16 years after menopause. The patterns of bone loss were, however, different for the axial and the peripheral skeleton. Thus, the bone loss in the distal forearm approached a more linear model with a more consistent bone loss throughout the observation period. In contrast, the lumbar spine showed no significant loss 8 years after menopause. This arrest in bone loss could not be explained by the presence of degenerative changes in the lumbar spine and/or aortic calcifications, although these changes significantly contributed to 14% increased bone mineral density (p < 0.001). We conclude that bone loss averages 20-25% over the initial 16 years of menopause regardless of skeletal site and that patterns of bone loss are different in the axial and peripheral skeleton.
Absorptiometry, Photon↗
Different effects of bisphosphonate and estrogen therapy on free and peptide-bound bone cross-links excretion.
We have measured the free and peptide-bound type I collagen cross-link excretions in normal women and in patients with metabolic bone disease using the HPLC technique and immunoassays recognizing specifically the free or peptide-bound forms of pyridinoline (Pyr). After menopause, free deoxypyridinoline (free D-Pyr) excretion measured by HPLC without urine hydrolysis and expressed as a fraction of the total excretion was lower than in premenopausal women (45 +/- 15% vs. 59 +/- 12%, p < 0.005), whereas the fraction of free Pyr was not changed. In normal pre- and postmenopausal women (n = 43), the fraction of free D-Pyr was negatively correlated with bone turnover rate as assessed by the total urinary excretion of Pyr (r = -0.64, p < 0.001). In patients with a variety of metabolic bone diseases characterized by increased bone turnover (osteoporosis, Paget's disease, and hyperthyroidism), the fractions of free Pyr and free D-Pyr were significantly lower than in premenopausal controls (p < 0.001 for all diseases). After 3 days of intravenous (iv) treatment with the bisphosphonate pamidronate in patients with Paget's disease and osteoporosis, the urinary excretion of cross-linked peptides measured by high performance liquid chromatography (HPLC) or enzyme-linked immunoassay (ELISA) (NTX and CrossLaps) was markedly decreased (-52% and -85% for NTX, -71% and -93% for CrossLaps in Paget's disease and osteoporosis, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Impact of soft tissue on in vivo accuracy of bone mineral measurements in the spine, hip, and forearm: a human cadaver study.
The impact of soft tissue in vivo on accuracy of bone mineral density (BMD) measurements of the spine and hip by dual energy X-ray absorptiometry and of the forearm by single photon absorptiometry was assessed by use of 14 human cadavers. The in vivo accuracy errors (SEE%) were: forearm 3-5%, anteroposterior spine 5.3%, lateral spine 10-12%, and femoral greater trochanter, neck, total, intertrochanteric, and Ward's triangle 3%, 6.5%, 6.7%, 8%, and 11-13%, respectively. Except from the lateral spine and the greater trochanter, the slopes of the linear regressions of in vivo BMD against in vitro BMD were not significantly different from 1 (p > 0.05). The calculated random accuracy error of BMD measurements due to fat inhomogeneity was estimated to 3-4% for the anteroposterior spine and 9-14% for the lateral spine (from abdominal computed tomography in 26 healthy women). In conclusion, acceptable accuracy errors below 6-7% (of soft tissue in vivo) of BMD measurements were obtained in the anteroposterior spine, the forearm, and the neck, greater trochanter, and total proximal femur.
Absorptiometry, Photon↗
Measurement of bone mineral density.
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Absorptiometry, Photon↗
Fitting Weibull duration models with random effects.
Duration time models often should include correlated failure times, due to clustered data. These random effects hierarchical models sometimes are called "frailty models" when used for survival analyses. The data analyzed here involve such correlations because patient level outcomes (the times until graft failure following kidney transplantation) are observed, but patients are clustered in different transplant centers. We describe fitting such models by combining two kinds of software, one for parametric survival regression models, and the other for doing Poisson regression in a hierarchical setting. The latter is implemented by using PRIMM (Poisson Regression and Interactive Multilevel Modeling) methods and software (Christiansen & Morris, 1994a). An illustrative example for profiling data is included with k = 11 kidney transplant centers and N = 412 patients.
Graft Survival↗
Early postmenopausal diminution of forearm and spinal bone mineral density: a cross-sectional study.
Diminution of bone mineral density (BMD) in the spine and forearm was studied cross-sectionally in 363 women who were 6 months to 10 years postmenopausal. BMD was determined by dual-energy X-ray absorptiometry (DXA) (Hologic QDR-2000) in the lumbar spine, in both the supine lateral (LAT) and anteroposterior (AP) projections, and in the distal third of the forearm. The postmenopausal diminution of BMD was best described by an exponential fit. The initial rate of postmenopausal diminution of BMD was highest in the most trabecular sites (LAT > AP > forearm), but 10-year diminution was similar at all sites (12%-13%, corresponding to about 1.0-1.5 SD), and extrapolation suggested reverse order of the rates of diminution thereafter (forearm > AP > LAT). When bone mineral content of the entire L3 vertebra (tBMC) was measured in vivo, AP tBMC could account for only 67% of the variation in LAT tBMC, compared with r2 = 0.997 in vitro. This observation suggests an accuracy problem in vivo in one of the spine measurement methods. We conclude that the initial rate of BMD diminution after the menopause seems to be highest in the spine, especially when measured laterally, but that this rate levels off within the first decade. The lower precision error of a forearm measurement (0.8% v 1.6 for AP and 3.1 for LAT) therefore implies that this method may require a shorter observation period than spine measurements for the detection of bone loss 5-10 years after menopause. Long-term longitudinal spine and forearm measurements are, however, needed to confirm these conclusions.
Absorptiometry, Photon↗
Circadian rhythm in type I collagen formation in postmenopausal women with and without osteopenia.
A circadian rhythm in the serum concentration of the procollagen type I carboxyl-terminal propeptide (sPICP) has previously been demonstrated in premenopausal women. This study was performed to investigate the circadian rhythm in sPICP in healthy and osteopenic postmenopausal women. Blood samples were taken every third hour for 27 h from three groups of women: 12 early postmenopausal women (aged 55 +/- 2 years; mean +/- SD); 12 late postmenopausal women (aged 73 +/- 1 years); and 12 osteopenic but otherwise healthy late postmenopausal women (aged 73 +/- 1 years). A circadian rhythm in sPICP was found in all three groups, as shown by cosinor analysis (p = 0.000003-0.03). The circadian rhythm in sPICP was significantly different between the osteopenic group and the age-matched healthy group (p < 0.008). The amplitude of the circadian rhythm in sPICP was about twice as high in the osteopenic group, and the time of the maximum tended to be about 3 h later, as compared with the age-matched healthy group. The plasma concentration of osteocalcin, as measured by a recently developed two-site enzyme-linked immunosorbent assay, also showed a circadian rhythm in all three groups (p = 0.0001-0.05), with no significant differences between groups. In conclusion, we have found a significant circadian rhythm in sPICP in both early and late postmenopausal women. In osteopenic women the nightly peak in sPICP is larger and persists later into the night as compared with non-osteopenic women.
Aged↗
Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy.
Hormone replacement therapy (HRT) prevents postmenopausal bone loss, and is therefore increasingly prescribed to prevent the development of postmenopausal osteoporosis. Because of individual differences in the response to HRT as well as problems with compliance, it has been debated how the skeletal response to HRT should be monitored. When estrogen production decreases at the menopause, a number of biochemical markers of bone turnover increase considerably in the order of 50%-100% from baseline. When HRT is instituted, the markers decrease again within the following 3-6 months. In the present prospective study we investigated whether the determination of biochemical markers of bone turnover may be useful for monitoring the skeletal effect of HRT. Seventy-six early postmenopausal women received HRT and 43 received placebo. The treatment period was 24 months and the women were followed with repeated bone mass measurements (every 3 months) which allowed calculation of the bone loss. Serum and urine samples were collected at 3, 6, 12 and 24 months. The placebo group lost a significant amount of bone mineral density in both the forearm and the spine (p < 0.001), whereas the HRT group did not. There was, however, a relatively large overlap of values between the HRT and placebo groups, especially in the spine. After 3 months' treatment the correlation between the changes in the markers and the bone loss was r = 0.59, and this value increased to r = 0.66 at 6 months and r = 0.76 and r = 0.77 at 12 and 24 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Biomarkers↗
Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry.
To assess the variation with age and menopause, 407 healthy normal women aged 18 to 75 years had body composition and fat distribution measured by dual-energy x-ray absorptiometry (DEXA). The mean +/- SD are given for different age decades. Postmenopausal women had significantly more fat, a more central fat distribution, and less lean tissue mass (LTM) than premenopausal women. In premenopausal and postmenopausal women, age only correlated with the abdominal to total-body fat tissue ratio (r approximately .24, P < .05), whereas the years since onset of menopause correlated with fat tissue mass (FTM), fat%, abdominal fat%, and the abdominal to total-body fat tissue ratio (r approximately .2, P < .05). To assess the independent impact of age, menopausal status, and years since menopause, multiple linear regressions were performed. FTM, fat%, and abdominal fat% were significantly related to menopausal status and years since menopause independently of age. The abdominal to total-body fat tissue ratio was statistically significantly related to age, but tended also to be independently related to years since menopause. LTM was statistically significantly related to menopausal status independently of age and years since menopause. In summary, we suggest that in healthy women total-body and abdominal fat may increase and LTM may decrease in the years after menopause, primarily in the perimenopausal years, without significant changes before menopause.
Absorptiometry, Photon↗
Creatinine clearance at menopause is not related to bone mass in later life.
OBJECTIVE: To investigate whether creatinine clearance (Ccr) at menopause is related to bone mass later in life. METHODS: Ccr was measured within 5 years after natural menopause in two groups of normal women. Bone mineral content (BMC) of the distal forearm, lumbar spine, and proximal femur were measured by photon absorptiometry and dual energy X-ray absorptiometry in these women 6 years (n = 47) and 14 years later (n = 98). RESULTS: Ccr corrected for body surface area just after the menopause did not correlate with BMC, 6.5 years and 14.5 years later. CONCLUSION: Low Ccr within the normal range at menopause is not an independent risk factor for osteopenia in later life.
Absorptiometry, Photon↗
Dual energy X-ray absorptiometry of the spine--decubitus lateral versus anteroposterior projection in osteoporotic women: comparison to single energy X-ray absorptiometry of the forearm.
We investigated the discriminatory ability of dual energy X-ray absorptiometry (DXA) of the lumbar spine in the anteroposterior vs. decubitus lateral projection in 53 elderly women with at least one vertebral fracture and 63 age-matched women without fracture. Twenty-three premenopausal healthy women served as a reference group. Spine measurements were compared to forearm measurements by single energy X-ray absorptiometry (SXA). Bone mineral density (BMD) of the women with fractures was 16% lower in the AP projection and 17% lower in the decubitus lateral projection compared to age-matched women without fractures. t-Scores (deviation from normal premenopausal values in SDs) were -2.1 to -2.3 in the women without fractures, and -3.9 (AP projection), -3.1 (lateral projection) and -3.8 (forearm) in the women with vertebral fractures. t-Scores as well as z-scores for bone mineral content of the vertebral body and the vertebral posterior elements (both measured with the lateral projection) were similar. ROC analysis showed no significant difference between the AP and the lateral projection of the spine. When subjects with vertebral endplate sclerosis (about 25% in each group, with considerably elevated spinal BMD) were excluded, it did not significantly change the diagnostic abilities for fractures. We found no diagnostic advantage of the lateral projection as compared to the AP projection or forearm measurement. Future studies will reveal whether absorptiometry in the lateral projection can be improved by supine lateral scanning.
Absorptiometry, Photon↗