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1.
Osteoporos Int ; 25(1): 151-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23912559

ABSTRACT

UNLABELLED: The effects of bariatric surgery on skeletal health are poorly understood. We found that bariatric surgery patients are more prone to fracture when compared to the general population. While further studies of fracture risk in this population are needed, bone health should be discussed in bariatric surgery clinics. INTRODUCTION: Bariatric surgery is an increasingly common treatment for medically complicated obesity. Adverse skeletal changes after bariatric surgery have been reported, but their clinical importance remains unknown. We hypothesized that bariatric surgery patients are at increased risk of fracture. METHODS: We conducted a historical cohort study of fracture incidence among 258 Olmsted County, Minnesota, residents who underwent a first bariatric surgery in 1985-2004. Relative fracture risk was expressed as standardized incidence ratios (SIRs), while potential risk factors were evaluated by hazard ratios (HR) obtained from a time-to-fracture regression model. RESULTS: The mean (±SD) body mass index at bariatric surgery was 49.0 ± 8.4 kg/m(2), with an average age of 44 ± 10 years and 82% (212) females. Gastric bypass surgery was performed in 94% of cases. Median follow-up was 7.7 years (range, 6 days to 25 years), during which 79 subjects experienced 132 fractures. Relative risk for any fracture was increased 2.3-fold (95% confidence interval (CI), 1.8-2.8) and was elevated for a first fracture at the hip, spine, wrist, or humerus (SIR, 1.9; 95% CI, 1.1-2.9), as well as for a first fracture at any other site (SIR, 2.5; 95% CI, 2.0-3.2). Better preoperative activity status was associated with a lower age-adjusted risk (HR, 0.4; 95% CI, 0.2-0.8) while prior fracture history was not associated with postoperative fracture risk. CONCLUSIONS: Bariatric surgery, which is accompanied by substantial biochemical, hormonal, and mechanical changes, is associated with an increased risk of fracture.


Subject(s)
Bariatric Surgery/adverse effects , Fractures, Bone/etiology , Adult , Body Mass Index , Cohort Studies , Female , Follow-Up Studies , Fractures, Bone/epidemiology , Fractures, Bone/physiopathology , Humans , Incidence , Male , Middle Aged , Minnesota/epidemiology , Obesity, Morbid/physiopathology , Obesity, Morbid/surgery , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Osteoporotic Fractures/physiopathology , Risk Factors
2.
Osteoporos Int ; 24(5): 1689-96, 2013 May.
Article in English | MEDLINE | ID: mdl-23212281

ABSTRACT

UNLABELLED: Adjusting for age, sex, and precipitating cause, the relative risk of death was increased following fractures at most skeletal sites. INTRODUCTION: This study aims to determine long-term survival following fractures due to any cause at each skeletal site. METHODS: In a historical cohort study, 2,901 Olmsted County, MN, USA, residents ≥35 years old who experienced any fracture in 1989-1991 were followed passively for up to 22 years for death from any cause. Standardized mortality ratios (SMRs) compared observed to expected deaths. RESULTS: During 38,818 person-years of follow-up, 1,420 deaths were observed when 1,191 were expected (SMR, 1.2; 95 % CI, 1.1-1.3). The overall SMR was greatest soon after fracture, especially among the men, but remained elevated for over a decade thereafter. Adjusting for age and sex, relative death rates were greater for pathological fractures and less for severe trauma fractures compared to the fractures due to no more than moderate trauma. In the latter group, long-term mortality was increased following fractures at many skeletal sites. After further adjustment for precipitating cause, overall SMRs were elevated not only following fractures at the traditional major osteoporotic sites (i.e., distal forearm, proximal humerus, thoracic/lumbar vertebrae, and proximal femur) combined (SMR, 1.2; 95 % CI, 1.1-1.3) but also following all other fracture types combined (SMR 1.2; 95 % CI, 1.1-1.4), excluding the hand and foot fractures not associated with any increased mortality. CONCLUSIONS: The persistence of increased mortality long after the occurrence of a fracture has generally been attributed to underlying comorbidity, but this needs to be defined in much greater detail if specific opportunities are to be identified for reducing the excess deaths observed.


Subject(s)
Fractures, Bone/mortality , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Fractures, Bone/etiology , Humans , Male , Middle Aged , Minnesota/epidemiology , Osteoporotic Fractures/mortality , Sex Distribution , Time Factors
3.
Osteoporos Int ; 23(6): 1721-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21909727

ABSTRACT

UNLABELLED: The incidence of non-hip femur fractures increased between 1984 and 2007, with an increase in the rates for women after 1996. INTRODUCTION: Recent reports have suggested that non-hip femur fractures may be decreasing over time, similar to proximal femur fractures. METHODS: Incidence rates for non-hip femur fractures among Olmsted County, Minnesota, residents were assessed before and after 1995 when the oral bisphosphonate, alendronate, was approved in the USA. RESULTS: From 1984 to 2007, 727 non-hip femur fractures were observed in 690 Olmsted County residents (51% female [median age, 71.6 years] and 49% male [21.4 years]). Altogether, 20% of the fractures were subtrochanteric, 51% were diaphyseal, and 29% involved the distal femur. Causes included severe trauma in 51%, minimal to moderate trauma in 34%, and pathologic causes in 15%. The overall age- and sex-adjusted annual incidence of first non-hip femur fracture was 26.7 per 100,000 (25.0 per 100,000 for women and 26.6 per 100,000 for men). Incidence rates increased with age and were greater in women than men. Between 1984-1995 and 1996-2007, age-adjusted rates increased significantly for women (20.4 vs. 28.7 per 100,000; p = 0.002) but not for men (22.4 vs. 29.5 per 100,000; p = 0.202). CONCLUSION: The incidence of first non-hip femur fractures rose between 1984 and 2007, with an increase in the rates for women after 1995.


Subject(s)
Femoral Fractures/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Diaphyses/injuries , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Minnesota/epidemiology , Sex Distribution , Young Adult
4.
AJNR Am J Neuroradiol ; 32(10): 1818-23, 2011.
Article in English | MEDLINE | ID: mdl-21998109

ABSTRACT

BACKGROUND AND PURPOSE: Vertebroplasty is an effective treatment for painful compression fractures refractory to conservative management. Because there are limited data regarding the survival characteristics of this patient population, we compared the survival of a treated with an untreated vertebral fracture cohort to determine whether vertebroplasty affects mortality rates. MATERIALS AND METHODS: The survival of a treated cohort, comprising 524 vertebroplasty recipients with refractory osteoporotic vertebral compression fractures, was compared with a separate historical cohort of 589 subjects with fractures not treated by vertebroplasty who were identified from the Rochester Epidemiology Project. Mortality was compared between cohorts by using Cox proportional hazards models adjusting for age, sex, and Charlson indices of comorbidity. Mortality was also correlated with pre-, peri-, and postprocedural clinical metrics (eg, cement volume use, RDQ score, analog pain scales, frequency of narcotic use, and improvement in mobility) within the treated cohort. RESULTS: Vertebroplasty recipients demonstrated 77% of the survival expected for individuals of similar age, ethnicity, and sex within the US population. Compared with individuals with both symptomatic and asymptomatic untreated vertebral fractures, vertebroplasty recipients retained a 17% greater mortality risk. However, compared with symptomatic untreated vertebral fractures, vertebroplasty recipients had no increased mortality following adjustment for differences in age, sex, and comorbidity (HR, 1.02; 95% CI, 0.82-1.25). In addition, no clinical metrics used to assess the efficacy of vertebroplasty were predictive of survival. CONCLUSIONS: Vertebroplasty recipients have mortality rates similar to those of individuals with untreated symptomatic fractures but have worse mortality compared with those with asymptomatic vertebral fractures.


Subject(s)
Fractures, Compression/mortality , Fractures, Compression/therapy , Osteoporosis/mortality , Osteoporosis/therapy , Spinal Fractures/mortality , Spinal Fractures/therapy , Vertebroplasty/mortality , Aged , Cohort Studies , Comorbidity , Female , Humans , Male , Minnesota/epidemiology , Prevalence , Risk Assessment , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome
5.
Leukemia ; 25(9): 1459-66, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21617698

ABSTRACT

Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and 'CLL-like' MBL is a precursor to CLL. We used flow cytometry to identify MBL from unaffected members of CLL kindreds. We identified 101 MBL cases from 622 study subjects; of these, 82 individuals with MBL were further characterized. In all, 91 unique MBL clones were detected: 73 CLL-like MBL (CD5(+)CD20(dim)sIg(dim)), 11 atypical MBL (CD5(+)CD20(+)sIg(+)) and 7 CD5(neg) MBL (CD5(neg)CD20(+)sIg(neg)). Extended immunophenotypic characterization of these MBL subtypes was performed, and significant differences in cell surface expression of CD23, CD49d, CD79b and FMC-7 were observed among the groups. Markers of risk in CLL such as CD38, ZAP70 and CD49d were infrequently expressed in CLL-like MBL, but were expressed in the majority of atypical MBL. Interphase cytogenetics was performed in 35 MBL cases, and del 13q14 was most common (22/30 CLL-like MBL cases). Gene expression analysis using oligonucleotide arrays was performed on seven CLL-like MBL, and showed activation of B-cell receptor associated pathways. Our findings underscore the diversity of MBL subtypes and further clarify the relationship between MBL and other lymphoproliferative disorders.


Subject(s)
B-Lymphocytes/pathology , Biomarkers, Tumor/genetics , Gene Expression Profiling , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Lymphocytosis/pathology , Biomarkers, Tumor/metabolism , Flow Cytometry , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Oligonucleotide Array Sequence Analysis , Prognosis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
6.
Osteoporos Int ; 22(12): 3047-54, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21308363

ABSTRACT

UNLABELLED: Bone strength at the ultradistal radius, quantified by micro-finite element modeling, can be predicted by variables obtained from high-resolution peripheral quantitative computed tomography scans. The specific formula for this bone strength surrogate (-555.2 + 8.1 × [trabecular vBMD] + 19.6 × [cortical area] + 4.2 × [total cross-sectional area]) should be validated and tested in fracture risk assessment. INTRODUCTION: The purpose of this study was to identify key determinants of ultradistal radius (UDR) strength and evaluate their relationships with age, sex steroid levels, and measures of habitual skeletal loading. METHODS: UDR failure load (~strength) was assessed by micro-finite element (µFE) modeling in 105 postmenopausal controls from an earlier forearm fracture case-control study. Predictors of bone strength obtained by high-resolution peripheral quantitative computed tomography (HRpQCT) in this group were then evaluated in a population-based cohort of 214 postmenopausal women. Sex steroids were measured by mass spectrometry. RESULTS: A surrogate variable (-555.2 + 8.1 × [trabecular vBMD] + 19.6 × [cortical area] + 4.2 × [total cross-sectional area]) predicted UDR strength modeled by µFE (R(2) = 0.81), and all parameters except total cross-sectional area declined with age. Evaluated cross-sectionally, the 21% fall in predicted bone strength between ages 40-49 years and 80+ years more resembled the change in trabecular volumetric bone mineral density (vBMD) (-15%) than that in cortical area (-41%). In multivariable analyses, measures of body composition and physical activity were stronger predictors of UDR trabecular vBMD, cortical area, total cross-sectional area, and predicted bone strength than were sex steroid levels, but bio-available estradiol and testosterone were correlated with body mass. CONCLUSIONS: Bone strength at the UDR, as quantified by µFE, can be predicted from variables obtained by HRpQCT. Predicted bone strength declines with age with changes in UDR trabecular vBMD and cortical area, related in turn to reduced skeletal loading and sex steroid levels. The predicted bone strength formula should be validated and tested in fracture risk assessment.


Subject(s)
Forearm/anatomy & histology , Models, Biological , Radius/anatomy & histology , Adult , Aged , Aged, 80 and over , Bone Density/physiology , Case-Control Studies , Female , Finite Element Analysis , Forearm/diagnostic imaging , Gonadal Steroid Hormones/analysis , Humans , Mass Spectrometry , Middle Aged , Postmenopause , Radius/diagnostic imaging , Risk Factors , Sex Factors , Tomography, X-Ray Computed/methods
7.
Osteoporos Int ; 22(5): 1627-31, 2011 May.
Article in English | MEDLINE | ID: mdl-20658128

ABSTRACT

SUMMARY: Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. INTRODUCTION: The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. METHODS: Twenty Vietnamese immigrants (age, 44-79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). RESULTS: The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. CONCLUSIONS: Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study.


Subject(s)
Asian People/statistics & numerical data , Bone Density/physiology , Adult , Aged , Biomarkers/blood , Bone Remodeling/physiology , Bone Resorption/blood , Bone Resorption/ethnology , Bone Resorption/physiopathology , Emigrants and Immigrants , Estradiol/blood , Female , Femur Neck/physiology , Humans , Lumbar Vertebrae/physiology , Middle Aged , Minnesota/epidemiology , Natriuretic Peptide, C-Type/blood , Radius/physiology , Tomography, X-Ray Computed/methods
8.
Osteoporos Int ; 21(7): 1161-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19714390

ABSTRACT

UNLABELLED: A diverse array of bone density, structure, and strength parameters were significantly associated with distal forearm fractures in postmenopausal women, but most of them were also correlated with femoral neck areal bone mineral density (aBMD), which provides an adequate measure of bone fragility at the wrist for routine clinical purposes. INTRODUCTION: This study seeks to test the clinical utility of approaches for assessing forearm fracture risk. METHODS: Among 100 postmenopausal women with a distal forearm fracture (cases) and 105 with no osteoporotic fracture (controls), we measured aBMD and assessed radius volumetric bone mineral density, geometry, and microstructure; ultradistal radius failure load was evaluated in microfinite element (microFE) models. RESULTS: Fracture cases had inferior bone density, geometry, microstructure, and strength. The most significant determinant of fracture in five categories were bone density (femoral neck aBMD; odds ratio (OR) per standard deviation (SD), 2.0; 95% confidence interval (CI), 1.4-2.8), geometry (cortical thickness; OR, 1.5; 95% CI, 1.1-2.1), microstructure (structure model index (SMI); OR, 0.5; 95% CI, 0.4-0.7), and strength (microFE failure load; OR, 1.8; 95% CI, 1.3-2.5); the factor-of-risk (applied load in a forward fall / microFE failure load) was 15% worse in cases (OR, 1.9; 95% CI, 1.4-2.6). Areas under receiver operating characteristic curves (AUC) ranged from 0.62 to 0.68. The predictors of forearm fracture risk that entered a multivariable model were femoral neck aBMD and SMI (combined AUC, 0.71). CONCLUSIONS: Detailed bone structure and strength measurements provide insight into forearm fracture pathogenesis, but femoral neck aBMD performs adequately for routine clinical risk assessment.


Subject(s)
Colles' Fracture/etiology , Osteoporotic Fractures/etiology , Absorptiometry, Photon/methods , Aged , Biomechanical Phenomena , Bone Density/physiology , Case-Control Studies , Colles' Fracture/pathology , Colles' Fracture/physiopathology , Female , Femur Neck/physiopathology , Humans , Middle Aged , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/pathology , Osteoporosis, Postmenopausal/physiopathology , Osteoporotic Fractures/pathology , Osteoporotic Fractures/physiopathology , Postmenopause/physiology , Radius/pathology , Risk Assessment/methods
9.
Osteoporos Int ; 20(5): 687-94, 2009 May.
Article in English | MEDLINE | ID: mdl-18797813

ABSTRACT

UNLABELLED: The decline in hip fracture incidence is now accompanied by a further reduction in the likelihood of a recurrent hip fracture among survivors of the first fracture. INTRODUCTION: Hip fracture incidence is declining in North America, but trends in hip fracture recurrence have not been described. METHODS: All hip fracture events among Olmsted County, Minnesota residents in 1980-2006 were identified. Secular trends were assessed using Poisson regression, and predictors of recurrence were evaluated with Andersen-Gill time-to-fracture regression models. RESULTS: Altogether, 2,752 hip fractures (median age, 83 years; 76% female) were observed, including 311 recurrences. Between 1980 and 2006, the incidence of a first-ever hip fracture declined by 1.37%/year for women (p < 0.001) and 0.06%/year for men (p = 0.917). Among 2,434 residents with a first-ever hip fracture, the cumulative incidence of a second hip fracture after 10 years was 11% in women and 6% in men with death treated as a competing risk. Age and calendar year of fracture were independently associated with hip fracture recurrence. Accounting for the reduction in first-ever hip fracture rates over time, hip fracture recurrence appeared to decline after 1997. CONCLUSION: A recent reduction in hip fracture recurrence is somewhat greater than expected from the declining incidence of hip fractures generally. Additional research is needed to determine the extent to which this can be attributed to improved patient management.


Subject(s)
Hip Fractures/epidemiology , Age Factors , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Minnesota/epidemiology , Recurrence , Risk Factors , Rural Health , Time Factors
10.
Neurology ; 67(2): 305-10, 2006 Jul 25.
Article in English | MEDLINE | ID: mdl-16864824

ABSTRACT

OBJECTIVE: Multiple sclerosis (MS) is approximately twice as common among women as men. If men have greater physiologic resistance to MS, they might theoretically require stronger genetic predisposition than women to overcome this resistance. In this circumstance, men would be expected to transmit the disease more often to their children, a phenomenon known as the Carter effect. The authors evaluated whether the Carter effect is present in MS. METHODS: The authors studied 441 children (45 with definite MS) of an affected father or mother (197 families of interest) from 3598 individuals in 206 multiplex pedigrees. The authors compared transmission of MS from affected men with transmission from affected women. RESULTS: Fathers with MS transmitted the disease to their children more often (transmitted: 18, not transmitted: 99) than mothers with MS (transmitted: 27, not transmitted: 296) (p = 0.032; OR: 1.99, 95% CI: 1.05, 3.77). Adjusting for both the sex of the affected child and multiple transmissions from a single affected parent, the sex of the affected parent remained as an independent risk factor for transmission of MS to children, fathers transmitting more often than mothers (p = 0.036; OR: 2.21, 95% CI: 1.05, 4.63). CONCLUSIONS: The authors have demonstrated the Carter effect in multiple sclerosis (MS). These observations may be explained by greater genetic loading in men that leads to relative excess paternal vs maternal transmission. Linkage analysis in genetic studies of MS may be more informative if patrilineal transmission were given additional weighting.


Subject(s)
Fathers/statistics & numerical data , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Heterozygote , Mothers/statistics & numerical data , Multiple Sclerosis/epidemiology , Multiple Sclerosis/genetics , Child , Female , Genetic Carrier Screening , Humans , Incidence , Male , Minnesota/epidemiology , Pedigree , Risk Assessment/methods , Risk Factors , Sex Distribution , Sex Factors
11.
Osteoporos Int ; 17(7): 978-85, 2006.
Article in English | MEDLINE | ID: mdl-16758138

ABSTRACT

INTRODUCTION: Approaches for recognizing vertebral fractures remain controversial. METHODS: An age-stratified population sample of 512 postmenopausal women was followed with serial radiographs for up to 12 years (4455 person-years). RESULTS: 112 women experienced a new vertebral fracture (20% reduction in any vertebral height from baseline) within this study period, for an annual age-adjusted (to US white women > or =50 years of age in 2000) incidence of 23 per 1000. Depending on the morphometric definition used, the prevalence of vertebral deformities at baseline ranged from 3 to 90%. A recent method to standardize vertebral heights produced the best agreement with a qualitative clinical reading of the films [kappa (kappa), 0.53]. Almost all of the different baseline definitions predicted future vertebral fractures, but most of the predictive power was attributable to the severe (e.g., 4 SD) deformities included within more generous (e.g., 3 SD) classifications. Whereas the generous definitions were more sensitive, and the restrictive ones more specific, their overall abilities to predict a new vertebral fracture were roughly comparable as evaluated by the c-index (analogous to the area under an ROC curve). CONCLUSION: This result suggests that the choice of a morphometry definition depends on the particular application and, in particular, on whether it is more important to maximize sensitivity or specificity.


Subject(s)
Spinal Fractures/etiology , Spine/pathology , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Postmenopause , Radiography , Risk Factors , Spine/diagnostic imaging
12.
J Neurol Neurosurg Psychiatry ; 76(12): 1693-7, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16291895

ABSTRACT

BACKGROUND: A pathological classification has been developed of early active multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I-T cell/macrophage associated; II-antibody/complement associated; III-distal oligodendrogliopathy, and IV-oligodendrocyte degeneration in the periplaque white matter. Mechanisms of demyelination in early MS may differ among the subgroups. Previous studies on biopsied MS have lacked clinicopathological correlation and follow up. Critics argue that observations are not generalisable to prototypic MS. OBJECTIVE: To describe the clinicopathological characteristics of the MS Lesion Project biopsy cohort. METHODS: Clinical characteristics and disability of patients with pathologically confirmed inflammatory demyelinating disease (excluding ADEM) classified immunopathologically (n = 91) and patients from the Olmsted County MS prevalence cohort (n = 218) were determined. RESULTS: Most patients who underwent biopsy and had pathologically proved demyelinating disease ultimately developed definite (n = 70) or probable (n = 12) MS (median follow up 4.4 years). Most had a relapsing remitting course and 73% were ambulatory (EDSS < or =4) at last follow up. Nine patients remained classified as having an isolated demyelinating syndrome at last follow up. Patients with different immunopathological patterns had similar clinical characteristics. Although presenting symptoms and sex ratios differed, the clinical course in biopsy patients was similar to the prevalence cohort. Median EDSS was <4.0 in both cohorts when matched for disease duration, sex, and age. CONCLUSIONS: Most patients undergoing biopsy, who had pathologically confirmed demyelinating disease, were likely to develop MS and remain ambulatory after a median disease duration of 4.4 years. The immunopathological patterns lacked specific clinical correlations and were not related to the timing of the biopsy. These data suggest that pathogenic implications derived largely from MS biopsy studies may be extrapolated to the general MS population.


Subject(s)
Demyelinating Diseases/pathology , Multiple Sclerosis/pathology , Adolescent , Adult , Aged , Biopsy , Child , Cohort Studies , Disease Progression , Female , Humans , Inflammation , Male , Middle Aged , Prognosis , Quality of Life
13.
Neurology ; 62(5): 811-4, 2004 Mar 09.
Article in English | MEDLINE | ID: mdl-15007140

ABSTRACT

The authors studied the association of an exon 4 (E4*epsilon2/3/4) and three promoter polymorphisms of APOE with disease course and severity stratified by gender in 221 patients with multiple sclerosis from two overlapping population-based prevalence cohorts. Women carriers of the E4*epsilon2 allele took longer to attain an Expanded Disability Status Scale score of 6 (p = 0.015) and had more favorable ranked severity scores than noncarriers (p = 0.009). There was no association in men. Alleles epsilon3 or epsilon4 and promoter polymorphisms were not associated with disease course or severity.


Subject(s)
Apolipoproteins E/genetics , Multiple Sclerosis/genetics , Adult , Apolipoprotein E4 , Female , Humans , Male , Multiple Sclerosis/physiopathology , Polymorphism, Genetic , Promoter Regions, Genetic , Severity of Illness Index , Sex Factors
14.
Osteoporos Int ; 13(7): 551-9, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12111015

ABSTRACT

The epidemiology of bone loss in populations of African heritage is still poorly known. We compared a convenience sample of 47 African-American (AA) residents of Rochester, Minnesota (32 women, 15 men) and 66 recent immigrants from Somalia (all women) with 684 white subjects (349 women, 335 men) previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm(2)) and volumetric bone mineral apparent density (BMAD, g/cm(3)) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 for white subjects and the QDR 4500 for the others; the instruments were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 18% higher in AA ( p<0.001) and 4% lower in Somali ( p = 0.147) than white women. Femoral neck BMD was 27% higher in AA women but also 11% greater in Somali women (both p<0.001) compared with whites. Lumbar spine BMD was 6% higher ( p = 0.132) and femoral neck BMD 21% higher ( p<0.001) in AA than white men. No Somali men were studied. After correcting for bone size differences, both lumbar spine ( p<0.01) and femoral neck BMAD ( p<0.001) were greater for Somali than white women, but the difference between Somali and AA women persisted. Lumbar spine and femoral neck BMAD values also remained significantly greater for AA women (both p<0.001) and men ( p<0.05; p<0.001) compared with whites. Weight was associated with BMAD at both skeletal sites in all groups, but adjustment for differences in weight did not reduce the discrepancy in BMAD values between Somali and AA women or between the latter group and whites. This heterogeneity among different ethnic groups of African heritage may provide an opportunity for research to better explain race-specific differences in bone metabolism.


Subject(s)
Black or African American , Bone Density/physiology , Osteoporosis/ethnology , Absorptiometry, Photon/methods , Adult , Age Factors , Aged , Black People , Female , Femur Neck/physiology , Humans , Linear Models , Lumbar Vertebrae/physiology , Male , Middle Aged , Osteoporosis/physiopathology , Somalia/ethnology , Statistics, Nonparametric , United States
15.
Bone ; 31(1): 119-25, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12110424

ABSTRACT

Secondary osteoporosis plays an important role in the pathogenesis of hip and spine fractures, but relatively little is known about the potential impact of secondary osteoporosis and fall-related disorders on the risk of distal forearm fractures. To address this issue, we conducted a population-based, nested case-control study comparing 496 Rochester, Minnesota, residents with an initial distal forearm fracture to an equal number of age- and gender-matched controls. Potential risk factors were assessed by review of each subject's complete (inpatient and outpatient) medical records in the community (median duration >30 years) and analyzed using multiple logistic regression. Although history of diabetes mellitus in women (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.15-0.75) and long-term anticonvulsant use in both genders (OR 3.58, 95% CI 1.26-10) were independently associated with fracture risk in a multivariate analysis, the conditions linked with secondary osteoporosis had, in aggregate, no statistically significant association with distal forearm fractures. Fall-related conditions altogether were associated with a borderline increase in risk (OR 1.36, 95% CI 0.98-1.91) and might have accounted for 19% of forearm fracture occurrence in the community. Among women (OR 2.72, 95% CI 1.20-6.19), but not men, a history of prior osteoporotic fracture was also associated with an increase in distal forearm fractures. These factors do not appear to account for the discrepancy in forearm fracture incidence in women when compared with men.


Subject(s)
Forearm Injuries/epidemiology , Fractures, Bone/epidemiology , Osteoporosis/epidemiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Confidence Intervals , Female , Forearm Injuries/etiology , Fractures, Bone/etiology , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Osteoporosis/complications , Risk Factors
16.
Osteoporos Int ; 12(11): 980-6, 2001.
Article in English | MEDLINE | ID: mdl-11804025

ABSTRACT

The overall risk of fracture following stroke has not been well quantified. We addressed this issue in a population-based retrospective cohort study among the 387 Rochester, Minnesota residents who survived for 90 days following their first cerebral infarction during the 10-year period, 1960-69. Cases were matched by age and sex to controls from the general population of Rochester, and subsequent fractures were assessed through review of each subject's complete (inpatient and outpatient) medical records in the community. With comparable follow-up, the 128 fractures observed among cases were little more than the 118 seen among controls, and the cumulative incidence of any fracture after 25 years was not significantly different (71% versus 66%; p=0.464). Using stratified Cox analysis, there was no increase in the risk of fractures generally (hazard ratio (HR), 1.1; 95% CI, 0.8-1.6) or hip fractures specifically (HR, 1.1; 95% CI, 0.6-2.1) compared with controls. Among the stroke patients with hemiparesis or hemiplegia, the majority of fractures occurred on the impaired side. In a multivariate analysis, fracture risk increased with age (HR per 10 years, 1.6; 95% CI, 1.4-2.0), with hospitalization at onset of stroke (HR, 2.0; 95% CI, 1.3-3.2) and with moderate functional impairment (HR, 1.6; 95% CI, 1.02-2.5) but not severe disability (HR, 0.8; 95% CI, 0.4-1.6). No other characteristic of the stroke or its treatment was an independent predictor of overall fracture risk. Patients and their caretakers need to be aware of the risk of fracture from falls, particularly when moderate impairment permits the patient to be independently mobile.


Subject(s)
Cerebral Infarction/complications , Fractures, Bone/etiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Life Tables , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Factors
17.
Mayo Clin Proc ; 76(12): 1199-203, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11761500

ABSTRACT

OBJECTIVE: To assess long-term secular trends in the utilization of bilateral compared with unilateral orchiectomy in the community. PATIENTS AND METHODS: This population-based descriptive study reviewed medical records of all Olmsted County, Minnesota, men undergoing orchiectomy between 1956 and 2000. RESULTS: Over the 45-year study period, 381 Olmsted County men had a first unilateral orchiectomy, while 431 underwent bilateral orchiectomy (including 8 with a second unilateral orchiectomy). There was no change over time in the age-adjusted utilization of unilateral orchiectomy, which was performed for a wide range of indications, mostly cryptorchidism and testicular malignancy. Most bilateral procedures, on the other hand, were in elderly men for castration, and trends over time generally paralleled those reported for prostate cancer in this community. CONCLUSION: The declining incidence of prostate cancer in recent years, combined with a shift to earlier stages and younger ages at diagnosis, and the development of pharmacological approaches to hormonal manipulation have led to a dramatic decline in the utilization of bilateral orchiectomy, while unilateral orchiectomy rates have remained unchanged.


Subject(s)
Orchiectomy/statistics & numerical data , Orchiectomy/trends , Patient Selection , Practice Patterns, Physicians'/trends , Prostatic Neoplasms/surgery , Age Distribution , Age Factors , Aged , Aged, 80 and over , Biopsy , Community Health Planning , Cryptorchidism/epidemiology , Cryptorchidism/surgery , Databases as Topic , Health Care Surveys , Humans , Incidence , Male , Middle Aged , Minnesota/epidemiology , Neoplasm Staging , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/pathology , Retrospective Studies , Testicular Neoplasms/epidemiology , Testicular Neoplasms/surgery
18.
Osteoporos Int ; 11(11): 977-83, 2000.
Article in English | MEDLINE | ID: mdl-11193251

ABSTRACT

There is growing awareness that therapeutic decision-making may be confounded by discrepancies in the prevalence of osteoporosis by World Health Organization criteria when bone density is measured at different skeletal sites. To explore this issue, we measured bone density at a variety of skeletal sites in a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years). Men had greater areal bone mineral density (BMD, g/cm2) than women at almost every subregion on total body, anteroposterior (AP) and lateral lumbar spine, proximal femur and forearm scans by dual-energy X-ray absorptiometry. However, adjustment for height or, where possible, calculation of bone mineral apparent density (BMAD, g/cm3) reduced or eliminated these differences. In addition, three different patterns of change in bone density over life were observed at the various skeletal sites as judged from cross-sectional data: no apparent age-related bone loss (e.g., AP spine BMD in men); linear bone loss over life in both sexes beginning in young adulthood (e.g., femoral neck BMD); and bone loss beginning around the time of menopause or a comparable age in men (e.g., midradius BMD). The various adjustments for bone size and the different patterns of age-related change in bone density had profound effects on the estimated prevalence of osteoporosis by World Health Organization criteria, which ranged from 2% to 45% among postmenopausal women and from 0 to 36% among men 50 years of age and older depending upon the skeletal parameter that was assessed. These observations emphasize the difficulties involved in attempts to standardize BMD scores and definitions of osteoporosis for clinical use.


Subject(s)
Body Constitution/physiology , Bone Density/physiology , Osteoporosis/diagnosis , Absorptiometry, Photon/methods , Adult , Age Factors , Aged , Aged, 80 and over , Body Height/physiology , Cross-Sectional Studies , Female , Forearm , Hip , Humans , Male , Middle Aged , Osteoporosis/physiopathology , Sex Factors , Spine
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