Biomedical subjects

Ann L Oberg

Publications and source records attributed to Ann L Oberg.

At least 19 recordsLinked to original sources

PubMed2006

A method for automatically interpreting mass spectra of 18O-labeled isotopic clusters.

16O/18O labeling is one differential proteomics technology among many that promises diagnostic and prognostic biomarkers of disease. Although the incorporation of 18O in the C-terminal carboxyl group during endoproteinase digestion in the presence of H2 18O makes the process of labeling facile, the ease and effectiveness of label incorporation have in some regards been outweighed by the difficulties in interpreting the resulting spectra. Complex isotope patterns result from the composition of unlabeled (18O(0)), singly labeled (18O(1)), and doubly labeled species (18O(2)) as well as contributions from the naturally occurring isotopes (e.g. 13C and 15N). Moreover because labeling is enzymatic, the number of 18O atoms incorporated can vary from peptide to peptide. Finally it is difficult to distinguish highly up-regulated from highly down-regulated or C-terminal peptides. We have developed an algorithm entitled regression analysis applied to mass spectrometry (RAAMS) that automatically, rapidly, and confidently interprets spectra of 18O-labeled peptides without requiring chemical composition information derived from product ion spectra. The algorithm is able to measure the effective 18O incorporation rate due to variable enzyme substrate specificity of the pseudosubstrate during the isotope exchange reaction and corrects for the 18O(0) abundance that remains in the labeled sample when using a two-step digestion/labeling procedure. We have also incorporated a method for distinguishing pure 18O(0) from pure 18O(2) peptides utilizing impure H2 18O. The algorithm operates on centroided peak lists and is therefore very fast: nine chromatograms of, on average, 1,168 spectra and containing, on average, 6,761 isotopic clusters were interpreted in, on average, 45 s per chromatogram. RAAMS is fast enough (average, 38 ms/spectrum) to allow the possibility of performing information-dependent MS/MS on a chromatographic time scale on species exceeding predetermined ratio thresholds. We describe in detail the operation of the algorithm and demonstrate its use on datasets with known and unknown ratios.

Algorithms↗

PubMed2006

Long-term fracture risk among women with proven endometriosis.

OBJECTIVE: To determine whether women with pelvic endometriosis are at increased fracture risk. DESIGN: Historical cohort study. SETTING: Population-based investigation using the data resources of the Rochester Epidemiology Project. PATIENT(S): From Olmsted County, Minnesota, 987 women with endometriosis that was first surgically visualized or histologically proven in 1970-1989. INTERVENTION(S): None, observational study. MAIN OUTCOME MEASURE(S): Follow-up for fractures through complete inpatient and outpatient community medical records. RESULT(S): In 17,408 person-years of follow-up, 256 women experienced 449 different fractures. The cumulative incidence after 20 years (30.8%) was not elevated relative to that expected (30.6%). The independent predictors of any fracture included age (hazard ratio [HR] per 10 years: 1.61; 95% confidence interval [CI] 1.42-1.84]), corticosteroid use (HR: 2.78; 95% CI 1.48-5.24), prior hip, spine, or forearm fracture (HR: 1.82; 95% CI 1.10-3.02), and use of the selective estrogen receptor modulators, tamoxifen or raloxifene (HR: 4.34; 95% CI 2.14-8.81); physical activity was protective (HR: 0.40; 95% CI 0.18-0.88). There was no significant influence on fracture risk of surgery or other medical treatments for endometriosis. CONCLUSION(S): Despite reported adverse effects of treatment on bone density, there was no overall increase in long-term fracture risk in this unselected cohort of women with proven endometriosis.

Adolescent↗

PubMed2006

Joint estimation of calibration and expression for high-density oligonucleotide arrays.

MOTIVATION: The need for normalization in microarray experiments has been well documented in the literature. Currently, many analysis methods treat normalization and analysis as a series of steps, with summarized data carried forward to the next step. RESULTS: We present a unified algorithm which incorporates normalization and class comparison in one analysis using probe level perfect match and mismatch data. The algorithm is based on calibration models common to most biological assays, and the resulting chip-specific parameters have a natural interpretation. We show that the algorithm fits into the statistical generalized linear models framework, describe a practical fitting strategy and present results of the algorithm applied to an example dataset as well as based on metrics used in affycomp. The algorithm ranks amongst the top third of the affycomp competitors, performing best in measures of bias. AVAILABILITY: R functions are available on request from the authors.

Algorithms↗

PubMed2006

Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study.

Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.

Adolescent↗

PubMed2006

Fracture risk after the diagnosis of Parkinson's disease: Influence of concomitant dementia.

In an inception cohort of 196 Olmsted County, Minnesota, residents with Parkinson's disease (PD) first recognized in 1976 to 1995, we tested whether the increased risk of bone fractures is associated with concomitant dementia. Using the data resources of the Rochester Epidemiology Project, information about PD, dementia, other clinical risk factors for fracture and fracture events was obtained from review of complete inpatient and outpatient medical records spanning each subject's residence in the community. Compared to an equal number of age- and sex-matched non-PD referent subjects from the community, PD patients were at a 2.2-fold increased risk of fractures generally and a 3.2-fold greater risk of hip fractures specifically. Adjusting for age, the independent predictors of overall fracture risk in the PD subjects included female sex (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.1-2.3), dementia (HR, 1.6; 95% CI, 1.1-2.4) and chronic depression, which was associated with a reduced risk (HR, 0.4; 95% CI, 0.2-0.8). Hip fractures were predicted by dementia (HR, 2.2; 95% CI, 1.2-4.1). The increased fracture risk in patients with PD is not entirely explained by concomitant dementia, and additional study is needed to determine the relative contributions to fracture risk of falls versus bone loss in these patients.

Adult↗

PubMed2006

Age- and sex-specific differences in the factor of risk for vertebral fracture: a population-based study using QCT.

UNLABELLED: We used QCT scans obtained in 687 men and women, 21-97 years of age, to estimate the factor of risk for vertebral fracture, Phi(vert), defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Phi(vert) increased significantly more in women than men. Age- and sex-specific differences in Phi(vert) closely resembled previously reported vertebral fracture incidence. INTRODUCTION: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility. MATERIALS AND METHODS: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Phi(vert)) in an age- and sex-stratified population-based sample of 700 women and men 21-97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1-L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Phi(vert), was computed as the ratio of spinal compressive force to vertebral strength for each activity. RESULTS: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (-43% versus -31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Phi(vert) increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Phi(vert-bending) exceeded 1.0 in 30% of women and 12% of men > or =50 years of age, values that are similar to the reported frequency of vertebral fracture. CONCLUSION: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.

Adult↗

PubMed2006

Does reduced skeletal loading account for age-related bone loss?

UNLABELLED: A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21-97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging. INTRODUCTION: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail. MATERIALS AND METHODS: In a stratified random sample of Rochester, MN, women and men 21-97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (H(o)) that bone strength per unit load did not vary with age. RESULTS AND CONCLUSIONS: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p = 0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.

Adult↗

PubMed2005

Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men.

CONTEXT: Using high-resolution three-dimensional peripheral quantitative computed tomography (3D-pQCT) imaging, we recently described sex and age effects on bone microstructure at the ultradistal radius in men and women. Although bone volume/tissue volume decreased with age in both sexes, changes in trabecular number (TbN) and thickness (TbTh) in men were complex, with evidence for conversion of thick trabeculae into more numerous, thinner trabeculae in young men. OBJECTIVE: Our objective was to define the relationship between hormonal and bone turnover variables and trabecular microstructure at the ultradistal radius. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based, cross-sectional study in the general community that included 205 women and 269 men, aged 21-97 yr. MAIN OUTCOME MEASURES: We measured correlation of bone volume/tissue volume, TbN, TbTh, and trabecular separation with hormonal and bone turnover variables. RESULTS: In young men (20-39 yr), TbTh and TbN were associated with serum IGF-I levels (r = 0.31, P < 0.05 and r = -0.35, P < 0.01, respectively). No associations were found between sex steroid levels (bioavailable estradiol or testosterone) or biochemical markers of bone turnover and trabecular parameters in young men or women. By contrast, in elderly men and women (>60 yr), sex steroids were the most consistently associated with trabecular microstructure, and bone turnover markers were variably associated with these parameters. CONCLUSIONS: In young men, the apparent conversion of thick trabeculae into more numerous, thinner trabeculae is most closely associated with declining IGF-I levels. By contrast, sex steroids are the major hormonal determinants of trabecular microstructure in elderly men and women.

Adult↗

PubMed2005

Population-based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures.

UNLABELLED: In an age- and sex-stratified population sample (n = 700), we estimated fall-related loads and bone strength indices at the UDR and FN. These load/strength ratios more closely simulated patterns of wrist and hip fractures occurring in the same population than did measurement of vBMD. INTRODUCTION: Areal BMD measurements, although associated with fracture risk, incompletely explain patterns of fragility fractures. Moreover, population-based assessments relating applied loads and whole bone strength to fracture patterns have not been made. MATERIALS AND METHODS: Using QCT, we assessed volumetric BMD (vBMD), cross-sectional geometry, and axial (EA) and flexural (EI) rigidities (indices of bone's resistance to compressive and bending loads, respectively) at the ultradistal radius (UDR) and femoral neck (FN) and estimated the loads applied to the wrist and hip during a fall. We used fall load (FL)/bone strength ratios to estimate fracture risk. RESULTS: vBMD in young adults was similar between sexes. Decreases in vBMD over life were also similar (30% and 28%) at UDR but were somewhat greater (46% and 34%) at FN in women versus men, respectively. In young adults, FL/strength ratios at UDR were 32-51% lower (better) in men than in women and increased (worsened) over life less in men (+4% to +22%) than in women (+20% to +33%). In young adults, FL/strength ratios at FN were only marginally better in men than in women but worsened less over life in men (+22% to +36%) than in women (+40% to +62%). CONCLUSIONS: The 6:1 female preponderance and the virtual immunity of men for age-related increases in wrist fractures are largely explained by the more favorable FL/strength ratios at UDR in young adult men (because of larger bone size and more favorable geometry) versus women and to maintaining this advantage over life. The 2-fold lower incidence of hip fractures in men versus women is largely explained by age-related increases (worsening) of FL/bone strength ratios that are only one-half of the increases in women. The moderate increases in these ratios with aging are insufficient to explain the >4-fold increase in hip fracture incidence after age 75 in both sexes, suggesting contributions of other factors, especially the well-documented increased frequency of injurious falls among the elderly.

Absorptiometry, Photon↗

PubMed2005

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

UNLABELLED: In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.

Adult↗

PubMed2005

Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease.

UNLABELLED: We updated the incidence of primary hyperparathyroidism in Rochester, Minnesota. The lower rates previously noted persisted, whereas parathyroidectomies at our institution remained high. These data suggest an etiologic factor may be responsible for the peak incidence in the 1970s. INTRODUCTION: Automated serum calcium measurements were associated with a dramatic rise in primary hyperparathyroidism in the early 1970s, but a progressive decline in the incidence thereafter was unexpected and suggested a fundamental change in the epidemiology of the disease. Our objective was to evaluate trends in the incidence of primary hyperparathyroidism since 1992. MATERIALS AND METHODS: In this population-based descriptive study, Rochester, MN, residents who met defined diagnostic criteria for primary hyperparathyroidism from January 1993 through December 2001 were identified through the medical record linkage system of the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System. Changes in incidence were evaluated by Poisson regression. RESULTS: Altogether, 136 Rochester residents (94 women and 42 men) were newly identified with primary hyperparathyroidism in 1993-2001. Their mean age was 56 years, and 93% had definite disease. The overall age- and sex-adjusted (to 2000 U.S. whites) rate during this period was 21.6 per 100,000 person-years, which was less than the annual rate of 29.1 per 100,000 observed in 1983-1992 and 82.5 per 100,000 in July 1974-1982. Although community incidence declined, the number of parathyroidectomies performed at our institution increased during the same period. Serum calcium was deleted from the automated chemistry panel in June 1996, but most subjects remained asymptomatic at diagnosis (95%) with mild hypercalcemia. The majority of subjects were observed without parathyroid surgery (75%), and there was minimal impact on patient management from the 1990 NIH consensus conference on asymptomatic primary hyperparathyroidism. CONCLUSIONS: The lower incidence of primary hyperparathyroidism noted through 1992 has persisted in our community through 2001, whereas parathyroidectomies at our institution remained high. These data suggest that some underlying etiologic factor, in addition to the introduction of automated serum calcium testing, may have been responsible for the peak incidence in the 1970s.

Calcium↗

PubMed2005

Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women.

CONTEXT: Although estrogen clearly plays a central role in regulating bone mass in women, studies in men have suggested that there may be a threshold bioavailable (bio) estradiol (E2) level below which aging men begin to lose bone and that the threshold for estrogen deficiency in cortical bone may be considerably lower than that in trabecular bone. There are no data testing this in women. OBJECTIVE: Our objective was to assess volumetric bone mineral density (vBMD) and bone geometry by quantitative computed tomography and relate these to circulating bio E2 and bio testosterone levels. DESIGN: We studied a cross-sectional, age-stratified population sample of 235 women (age, 21-97 yr). RESULTS: vBMD/structural parameters were not related to sex steroid levels in young premenopausal women (age, 20-39 yr) with a median bio E2 level of 17 pg/ml (63 pmol/liter). By contrast, bio E2 and bio testosterone levels were both significantly associated with trabecular and cortical vBMD and cortical area at multiple sites in late postmenopausal women (age > or = 60 yr) who had a median bio E2 level of 3 pg/ml (11 pmol/liter). Late premenopausal and early postmenopausal women (age, 40-59 yr) with an intermediate median bio E2 level of 11 pg/ml (42 pmol/liter) showed age-adjusted correlations of bio E2 levels with trabecular but not with cortical vBMD. CONCLUSIONS: In women, bio E2 levels are associated with vBMD and some structural bone parameters at low but not high bio E2 levels. Similar to findings in men, the threshold for estrogen deficiency in cortical bone in women appears to be lower than that in trabecular bone.

Adult↗

PubMed2005

Statistical evaluation of internal and external mass calibration laws utilized in fourier transform ion cyclotron resonance mass spectrometry.

The statistical evaluation of two common and three new calibration laws utilized in Fourier transform ion cyclotron resonance mass spectrometry are presented. Electrospray ionization was used to prepare a series of mass spectra of ammonium-adducted polypropylene glycol (PPG) with an average molecular weight of 1000 Da. The singly charged PPG-1000 oligomers allowed for the description of a broad range of m/z and abundance values within each mass spectrum. The hexapole accumulation time was varied to afford a range of total ion abundance values of about an order of magnitude. To examine each of the calibration laws, we utilized cross-validation both "within-spectrum" and "between-spectra" for internally and externally calibrated data, respectively. In addition, we used t-statistics to ensure that each calibration coefficient was statistically significant and necessary to accurately describe the variation in the data. In comparison to commonly used calibration laws for internal calibration, our new calibration law based on multiple linear regression offered a 2-fold improvement in mass measurement accuracy (MMA). In comparison to external calibration laws without automatic gain control, our new calibration law using multiple regression improved the MMA by >10-fold; this improvement would increase further as the dynamic range of the measurement increases (e.g., a biological system). For both our internal and external calibration laws, the median MMA was less than 1 part-per-million. Furthermore, we investigate the number of calibrant ions as well as their required m/z range in order to successfully achieve high MMA.

Calibration↗

PubMed2005

Contributions of bone density and structure to fracture risk assessment in men and women.

Although bone mineral density (BMD) is a strong predictor of fractures, it is only a surrogate for bone strength. Bone structural parameters can now be measured on BMD scans, but it is unclear whether they would be more useful for risk assessment. We measured structural parameters using the Hip Structural Analysis Program and evaluated their association, compared with standard hip BMD, with fracture risk in a population-based sample of 213 postmenopausal women and 200 men > or =50 years of age. Altogether, 38% of the women and 27% of the men had experienced a fracture due to moderate trauma (half involved hip, spine or distal forearm), while 23% and 36%, respectively, had a previous fracture due to severe trauma. In logistic regression analyses adjusted for age, the hip BMD and structural parameters were all associated with moderate trauma fractures generally, and osteoporotic fractures specifically, in women, but the best predictor in a multivariate model was femoral neck BMD (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.9-4.0). BMD and the structural parameters were strongly correlated, however, and could be interchanged with little reduction in predictive power. These variables were less predictive of moderate trauma fractures in men. The best model included age (OR per 10 years, 1.5; 95% CI, 1.1-2.1), femoral neck section modulus (OR, 1.6; 95% CI, 1.1-2.5) and intertrochanteric buckling ratio (OR, 1.6; 95% CI, 1.3-2.0). Correction for body size did not alter these relationships. Fractures due to severe trauma were best predicted by structural parameters: in women, femoral neck buckling ratio (OR, 1.2; 95% CI, 1.04-1.5) and, in men, intertrochanteric buckling ratio (OR, 1.4; 95% CI, 1.2-1.6). These data suggest that selected structural variables as assessed by dual-energy X-ray absorptiometry would be as good as standard BMD measurements for predicting fracture risk. Because of the strong correlations, however, some judgment can be used in selecting the variables easiest to measure.

Absorptiometry, Photon↗

PubMed2005

Long-term trends in thyroid carcinoma: a population-based study in Olmsted County, Minnesota, 1935-1999.

OBJECTIVE: To determine whether there was a significant increase in the incidence of thyroid carcinoma in Olmsted County, Minnesota, that may be attributed to the widespread use of therapeutic head and neck irradiation between 1920 and the 1950s or to exposure to atomic fallout at the Nevada Test Site in the 1960s. METHODS: Rochester Epidemiology Project resources were used to identify potential cases of thyroid carcinoma among residents of Olmsted County between 1935 and 1984. We extended this earlier study through 1999. RESULTS: During the study period, thyroid carcinoma was newly diagnosed in 263 residents. In women, the age-adjusted incidence increased from 2.7 per 100,000 person-years (p-y) in 1935-1949 to 9.2 per 100,000 p-y in 1990-1999 (P = .001); In men, the rate increased from 0.8 to 5.0 per 100,000 p-y (P = .007). However, most of the increase occurred before 1965 and remained relatively stable thereafter. Similar trends were observed for papillary carcinoma alone. CONCLUSION: Although the Incidence of thyroid carcinoma increased significantly between 1935 and 1964, no significant Increases have been seen since 1965, suggesting that neither atmospheric atomic fallout from the Nevada Test Site nor use of ionizing radiation to treat conditions of the head and neck significantly affected the incidence of thyroid carcinoma in Olmsted County.

Adolescent↗

PubMed2004

Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men.

UNLABELLED: In a population-based, cross-sectional study, we related age-associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated "threshold" for skeletal estrogen deficiency was most evident at cortical sites. INTRODUCTION: Serum sex steroids, particularly estrogen levels, are associated with bone mass in men, and previous work has suggested that there may be a "threshold" bioavailable estradiol (bio E(2)) level below which the male skeleton becomes estrogen deficient. However, previous studies addressing this issue have exclusively used DXA, which cannot separate trabecular from cortical bone or provide information on bone geometry or structure. MATERIALS AND METHODS: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E(2) and bio testosterone (T) levels. RESULTS: Compared with young men (age, 20-39 years), middle-aged men (age, 40-59 years) had significantly lower bio T (-26%, p < 0.001) and bio E(2) (-9%, p = 0.038) levels, and these decreases were even greater in the elderly men (age > or = 60 years, -60% and -38% for bio T and bio E(2), respectively, p < 0.001 for both). Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E(2) levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E(2) and bio T at some sites. At all cortical sites, vBMD was associated with bio E(2) at low (<30 pM, R = 0.27-0.41, p < 0.05-0.001) but not high (> or =30 pM, R = -0.003 to 0.12, p = not significant) levels; no such differences were evident at trabecular sites. CONCLUSIONS: In men, bio E(2) is the most consistent predictor of vBMD and some bone geometric variables as assessed by QCT. We also extend our previous findings on a possible "threshold" for skeletal estrogen deficiency by showing that this is most evident for cortical sites.

Adult↗

PubMed2004

Long-term fracture risk among children with asthma: a population-based study.

UNLABELLED: Fracture risk among patients diagnosed with asthma in childhood is greater in males and oral corticosteroid users, but most fractures are of the appendicular skeleton and may relate to impaired skeletal development. INTRODUCTION: There are no population-based data on fracture outcomes among the growing number of patients with asthma diagnosed in childhood. MATERIALS AND METHODS: We conducted a population-based retrospective (historical) cohort study among 279 Rochester, Minnesota, residents who were <35 years of age (mean, 6.2 years) when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and cases were compared directly with age- and sex-matched controls in a stratified proportional hazards model. Risk factors for fractures among the asthma cases were assessed using Andersen-Gill time-to-fracture regression models. RESULTS: During 6649 person-years of follow-up (median, 24.3 years/subject), 107 asthma patients experienced 189 fractures, for a crude fracture incidence rate of 2.8 per 100 person-years. The actuarially estimated cumulative fracture incidence after 20 years was 40% compared with 34% among controls (p = 0.122). There was no significant increase in overall fracture risk among cases compared to their age- and sex-matched controls (hazard ratio [HR], 1.3; 95% CI, 0.9-1.9), but males with asthma had a 2.6-fold greater risk of hand and finger fractures than control males. The independent predictors of overall fracture risk among the asthma patients included male gender (HR, 2.2; 95% CI, 1.5-3.2) and use of oral corticosteroids (HR, 2.0; 95% CI, 1.2-3.1) or anti-cholinergic agents (HR, 3.9; 95% CI, 1.5-10). CONCLUSIONS: Rather than osteoporotic fractures of the axial skeleton, oral corticosteroid therapy was associated here with limb fractures, suggesting a relationship with impaired development of a biomechanically competent skeleton. Additional studies are needed to assess this possibility.

Adolescent↗

PubMed2004

Evaluation of a prediction model for long-term fracture risk.

UNLABELLED: The NOF cost-effectiveness model, based on clinical risk factors and femoral neck aBMD, predicted overall fracture risk in a cohort of postmenopausal women followed for up to 22 years. INTRODUCTION: To assess the ability of a statistical model to predict long-term fracture risk for a population of postmenopausal women, we compared observed fractures to those predicted by the National Osteoporosis Foundation's (NOF) cost-effectiveness model. MATERIALS AND METHODS: In this population-based study, 393 postmenopausal Rochester, MN, women had baseline measurements of femoral neck areal BMD (aBMD) and assessment of the clinical risk factors (personal fracture history, family history of osteoporotic fracture, low body weight, and smoking status) that were included in the NOF model. They were then followed prospectively for up to 22 years. Fractures were ascertained by periodic interview and review of community medical records. Standardized incidence ratios (SIRs) compared observed fractures to predicted numbers. RESULTS: During 4782 person-years of follow-up, 212 women experienced 503 fractures, two-thirds of which were caused by moderate trauma. When undiagnosed (incidentally noted) vertebral and rib fractures were excluded, there was general concordance between observed and predicted fractures of the hip (SIR, 0.78; 95% CI, 0.56-1.01), distal forearm (SIR, 1.22; 95% CI, 0.86-1.68), spine (SIR, 0.76; 95% CI, 0.50-1.11), and all other sites combined (SIR, 1.18; 95% CI, 0.97-1.42). Fracture prediction by the NOF model was about as good after 10 years as it was earlier during follow-up. CONCLUSIONS: This study validates the ability of a statistical model based on femoral neck aBMD and common clinical risk factors to predict the actual occurrence of fractures in a cohort of postmenopausal white women.

Absorptiometry, Photon↗