L J Melton

Mayo Foundation for Medical Education and Research, Jacksonville, FL, United States

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Publications (407)2962.52 Total impact

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    ABSTRACT: There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS-FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS-FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS-FN was greater than 2 SD for 2.5 % of women and between 1 and 2 SD for 21 %. ΔLS-FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95 % CI = 1.04-1.15). In reclassification analyses, only 2.3-3.2 % of the women moved to a higher or lower risk category when using FRAX with ΔLS-FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1-2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. This might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.
    Calcified Tissue International 09/2014; · 2.50 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the United States (U.S.) population. Stored serum samples from National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999-2004 were available for 12 482 persons age 50 years (2331 'black', 2475 Hispanics, 7051 'white', and 625 'others') on which agarose-gel electrophoresis, serum protein immunofixation, serum free light-chain assay, and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the U.S., respectively (P=0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in prevalence of MGUS between the North/Midwest versus the South/West regions of the U.S. was found, which has etiologic implications.Leukemia accepted article preview online, 20 January 2014. doi:10.1038/leu.2014.34.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2014; · 10.16 Impact Factor
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    ABSTRACT: To assess recent trends in fracture incidence from all causes at all skeletal sites, we used the comprehensive (inpatient and outpatient) data resources of the Rochester Epidemiology Project to estimate rates for Olmsted County, Minnesota, residents in 2009-1, compared to similar data from 1989-1. During the three-year study period, 2009-11, 3549 residents ≥ 50 years of age experienced 5244 separate fractures. The age- and sex-adjusted (to the 2010 United States white population) incidence of any fracture was 2704 per 100,000 person-years (95% CI 2614-2793) and that for all fractures was 4017 per 100,000 (95% CI 3908-4127). Fracture incidence increased with age in both sexes, but age-adjusted rates were 49% greater among the women. Overall, comparably adjusted fracture incidence rates increased by 11% (from 3627 to 4017 per 100,000 person-years; p = 0.008) between 1989-1 and 2009-2011. This was mainly due to a substantial increase in vertebral fractures (+47% for both sexes combined), which was partially offset by a decline in hip fractures (-25%) among the women. There was also a 26% reduction in distal forearm fractures among the women; an increase in distal forearm fractures among men age 50 years and over was not statistically significant. The dramatic increase in vertebral fractures, seen in both sexes and especially after age 75 years, was attributable in part to incidentally-diagnosed vertebral fractures. However, the fall in hip fracture incidence, observed in most age-groups, continues the steady decline observed among women in this community since 1950. More generally, these data indicate that the dramatic increases in the incidence of fractures at many skeletal sites that were observed decades ago have now stabilized.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2013; · 6.04 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. Bariatric surgery, which is accompanied by substantial biochemical, hormonal, and mechanical changes, is associated with an increased risk of fracture.
    Osteoporosis International 08/2013; · 4.04 Impact Factor
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    ABSTRACT: 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.
    Osteoporosis International 12/2012; · 4.04 Impact Factor
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    ABSTRACT: We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgGλ in IgGκ MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC-pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5-3.7; P<0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1-3.00; P=0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology.Leukemia advance online publication, 3 August 2012; doi:10.1038/leu.2012.189.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2012; · 10.16 Impact Factor
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    ABSTRACT: We used a microsimulation model to estimate the threshold body weights at which screening bone densitometry is cost-effective. Among women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to identify those for whom bone densitometry is cost-effective. INTRODUCTION: Bone densitometry may be more cost-effective for those with lower body weight since the prevalence of osteoporosis is higher for those with low body weight. Our purpose was to estimate weight thresholds below which bone densitometry is cost-effective for women and men without a prior clinical fracture at ages 55, 60, 65, 75, and 80 years. METHODS: We used a microsimulation model to estimate the costs and health benefits of bone densitometry and 5 years of fracture prevention therapy for those without prior fracture but with femoral neck osteoporosis (T-score ≤ -2.5) and a 10-year hip fracture risk of ≥3%. Threshold pre-test probabilities of low BMD warranting drug therapy at which bone densitometry is cost-effective were calculated. Corresponding body weight thresholds were estimated using data from the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men (MrOS) study, and the National Health and Nutrition Examination Survey (NHANES) for 2005-2006. RESULTS: Assuming a willingness to pay of $75,000 per quality adjusted life year (QALY) and drug cost of $500/year, body weight thresholds below which bone densitometry is cost-effective for those without a prior fracture were 74, 90, and 100 kg, respectively, for women aged 55, 65, and 80 years; and were 67, 101, and 108 kg, respectively, for men aged 55, 75, and 80 years. CONCLUSIONS: For women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to select those for whom bone densitometry is cost-effective.
    Osteoporosis International 02/2012; · 4.04 Impact Factor
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    ABSTRACT: Using combined dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography, we demonstrate that men matched with women for femoral neck (FN) areal bone mineral density (aBMD) have lower volumetric BMD (vBMD), higher bone cross-sectional area, and relatively similar values for finite element (FE)-derived bone strength. aBMD by DXA is widely used to identify patients at risk for osteoporotic fractures. aBMD is influenced by bone size (i.e., matched for vBMD, larger bones have higher aBMD), and increasing evidence indicates that absolute aBMD predicts a similar risk of fracture in men and women. Thus, we sought to define the relationships between FN aBMD (assessed by DXA) and vBMD, bone size, and FE-derived femoral strength obtained from quantitative computed tomography scans in men versus women. We studied men and women aged 40 to 90 years and not on osteoporosis medications. In 114 men and 114 women matched for FN aBMD, FN total cross-sectional area was 38% higher (P < 0.0001) and vBMD was 16% lower (P < 0.0001) in the men. FE models constructed in a subset of 28 women and 28 men matched for FN aBMD showed relatively similar values for bone strength and the load-to-strength ratio in the two groups. In this cohort of young and old men and women from Rochester, MN, USA who are matched by FN aBMD, because of the offsetting effects of bone size and vBMD, femoral strength and the load-to-strength ratio tended to be relatively similar across the sexes.
    Osteoporosis International 11/2011; 23(1):155-62. · 4.04 Impact Factor
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    ABSTRACT: The incidence of non-hip femur fractures increased between 1984 and 2007, with an increase in the rates for women after 1996. Recent reports have suggested that non-hip femur fractures may be decreasing over time, similar to proximal femur fractures. 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. 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). The incidence of first non-hip femur fractures rose between 1984 and 2007, with an increase in the rates for women after 1995.
    Osteoporosis International 09/2011; 23(6):1721-6. · 4.04 Impact Factor
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    ABSTRACT: This analysis examines lumbar spine bone mineral density (BMD) of US adults from NHANES 2005-2008 by age, sex, and race/ethnicity. Prevalence of low spine BMD and agreement between the prevalence of low BMD at the spine and femur neck in older adults are also assessed. Lumbar spine BMD data from a representative sample of the US population have not been previously available. We used data from the National Health and Nutrition Examination Survey 2005-2008 to examine demographic patterns in lumbar spine BMD among US adults age ≥20 years and the prevalence of low lumbar spine BMD in adults age ≥50 years. Agreement between the prevalence of low BMD at the femur neck and spine in older adults was also assessed. Dual-energy X-ray absorptiometry was used to measure lumbar spine and femur neck BMD. World Health Organization definitions were used to categorize skeletal status as normal, osteopenia, or osteoporosis. Compared to non-Hispanic whites, non-Hispanic blacks had higher and Mexican Americans had lower lumbar spine BMD. Lumbar spine BMD declined with age in women, but not in men. Approximately 4.7 million (10%) older US women and 1 million (3%) older men had lumbar spine osteoporosis in 2005-2008. Roughly one third of them differed in skeletal status at the spine and hip but most were normal at one site and osteopenic at the other. Only 3-10%, depending on sex, had osteoporosis at one skeletal site but not at the other skeletal site. Between 76% and 87% with discordant skeletal status had lumbar spine T-scores within 1 unit of the category threshold. These findings suggest that measuring either the femur neck or the lumbar spine will correctly classify the majority of individuals who present for care as osteoporotic or not.
    Osteoporosis International 07/2011; 23(4):1351-60. · 4.04 Impact Factor
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    ABSTRACT: This analysis of National Health and Nutrition Examination Survey (NHANES) 2005-2008 data describes the prevalence of risk factors for osteoporosis and the proportions of men and postmenopausal women age 50 years and older who are candidates for treatment to lower fracture risk, according to the new Fracture Risk Assessment Tool (FRAX)-based National Osteoporosis Foundation Clinician's Guide. It is important to update estimates of the proportions of the older US population considered eligible for pharmacologic treatment for osteoporosis for purposes of understanding the health care burden of this disease. This is a cross-sectional study of the NHANES 2005-2008 data in 3,608 men and women aged 50 years and older. Variables in the analysis included race/ethnicity, age, lumbar spine and femoral neck bone mineral density, risk factor profiles, and FRAX 10-year fracture probabilities. The prevalence of osteoporosis of the femoral neck ranged from 6.0% in non-Hispanic black to 12.6% in Mexican American women. Spinal osteoporosis was more prevalent among Mexican American women (24.4%) than among either non-Hispanic blacks (5.3%) or non-Hispanic whites (10.9%). Treatment eligibility was similar in Mexican American and non-Hispanic white women (32.0% and 32.8%) and higher than it was in non-Hispanic black women (11.0%). Treatment eligibility among men was 21.1% in non-Hispanic whites, 12.6% in Mexican Americans, and 3.0% in non-Hispanic blacks. Nineteen percent of older men and 30% of older women in the USA are at sufficient risk for fracture to warrant consideration for pharmacotherapy.
    Osteoporosis International 06/2011; 23(3):811-20. · 4.04 Impact Factor
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    ABSTRACT: 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. 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. 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). 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. 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.
    Osteoporosis International 05/2011; 22(5):1627-31. · 4.04 Impact Factor
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    ABSTRACT: This analysis compares femur neck bone mineral density (FNBMD) and bone determinants in adults between National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2005-2008. FNBMD was higher in NHANES 2005-2008 than in NHANES III, but between-survey differences varied by age, sex, and race/ethnicity. The likelihood that FNBMD has improved appears strongest for older white women. Recent data on hip fracture incidence and femur neck osteoporosis suggest that the skeletal status of older US adults has improved since the 1990s, but the explanation for these changes remains uncertain. The present study compares mean FNBMD of adults ages 20 years and older between the third (NHANES III, 1988-1994) and NHANES 2005-2008. Dual-energy X-ray absorptiometry systems (pencil beam in NHANES III, fan beam in NHANES 2005-2008) were used to measure hip BMD, and several bone determinants are compared between surveys to assess their potential role in explaining observed FNBMD differences. FNBMD was higher overall in NHANES 2005-2008 than in NHANES III, but between-survey differences varied by age, sex, and race/ethnicity. Although FNBMD differences in several groups were small enough (≤3%) to be attributable to use of different dual-energy X-ray absorptiometry (DXA) systems in the two surveys, variability in size and direction of the differences does not support artifactual differences in DXA methodology as the sole explanation. Several FNBMD determinants (body size, smoking, selected bone-active medications, self-reported health status, calcium intake, and caffeine consumption) changed in a bone-improving direction in older adults, but FNBMD in older non-Hispanic white women remained significantly higher in 2005-2008 even after adjusting for DXA methodology or for the selected bone determinants. The likelihood that FNBMD has improved appears strongest for older white women, but the reason for the improvement in this group remains unclear.
    Osteoporosis International 04/2011; 23(2):771-80. · 4.04 Impact Factor
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    ABSTRACT: Osteoporosis constitutes a major public health problem through its association with age-related fractures, most notably those of the proximal femur. Substantial geographic variation has been noted in the incidence of hip fracture throughout the world, and estimates of recent incidence trends have varied widely. Studies in the published literature have reported an increase, plateau, and decrease in age-adjusted incidence rates for hip fracture among both men and women. Accurate characterisation of these temporal trends is important in predicting the health care burden attributable to hip fracture in future decades. We therefore conducted a review of studies worldwide, addressing secular trends in the incidence of hip and other fractures. Studies in western populations, whether in North America, Europe or Oceania, have generally reported increases in hip fracture incidence through the second half of the last century, but those continuing to follow trends over the last two decades have found that rates stabilise with age-adjusted decreases being observed in certain centres. In contrast, some studies suggest that the rate is rising in Asia. This synthesis of temporal trends in the published literature will provide an important resource for preventing fractures. Understanding the reasons for the recent declines in rates of hip fracture may help understand ways to reduce rates of hip fracture worldwide.
    Osteoporosis International 04/2011; 22(5):1277-88. · 4.04 Impact Factor
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    ABSTRACT: This analysis of National Health and Nutrition Examination Survey III data found a significant risk of incident hip fracture in adults aged 65 years and older who are candidates for treatment to lower fracture risk, according to the new National Osteoporosis Foundation Clinician's Guide. The relationship between treatment eligibility by the new National Osteoporosis Foundation (NOF) Guide to the Prevention and Treatment of Osteoporosis and the risk of subsequent hip fracture is unknown. The study sample consisted of 3,208 men and women ages 65 years and older who were examined in the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), a nationally representative survey. Risk factors used to define treatment eligibility at baseline were measured in NHANES III or were simulated using World Health Organization study cohorts. Incident hip fractures were ascertained using linked mortality and Medicare records that were obtained for NHANES III participants through December 31, 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of hip fracture by treatment eligibility status. The RR for subsequent hip fracture was 4.9 (95% CI 3.30, 7.94) in treatment-eligible vs treatment-ineligible persons. The increased risk for treatment-eligible persons remained statistically significant when examined by sex or age: RR(men) = 5.5 (2.6, 11.4) and RR(women) = 4.3 (2.2, 8.4); RR(65-79 y) = 4.8 (2.6, 8.7) and RR(80+ y) = 4.6 (2.1, 10.1). Treatment-eligible persons were about five times more likely to experience a subsequent hip fracture than the non-eligible persons. The new NOF guidelines appear to predict future hip fracture risk equally in men as in women, and fracture risk prediction did not appear to diminish with age.
    Osteoporosis International 02/2011; 22(2):541-9. · 4.04 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. 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.
    Osteoporosis International 02/2011; 22(12):3047-54. · 4.04 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    American Journal of Neuroradiology 01/2011; 32(10):1818-23. · 3.17 Impact Factor
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    ABSTRACT: Despite increasing prevalence, the economic implications of coeliac disease are just emerging. To assess the impact of coeliac disease diagnosis on healthcare costs and the incremental costs associated with coeliac disease. Administrative data for a population-based cohort of coeliac disease cases and matched controls from Olmsted County, Minnesota were used to compare (i) direct medical costs 1 year pre- and post-coeliac disease diagnosis for 133 index cases and (ii) 4-year cumulative direct medical costs incurred by 153 index cases vs. 153 controls. Analyses exclude diagnostic-related and out-patient pharmaceutical costs. Average total costs were reduced by $1764 in the year following diagnosis (pre-diagnosis cost of $5023 vs. $3259; 95% CI of difference: $688 to $2993). Over a 4-year period, coeliac disease cases experienced higher out-patient costs (mean difference of $1457; P = 0.016) and higher total costs than controls (mean difference of $3964; P = 0.053). Excess average total costs were concentrated among males with coeliac disease ($14,191 vs. $4019 for male controls; 95% CI of difference: $2334 to $20,309). Coeliac disease-associated costs indicate a significant economic burden of disease, particularly for diseased males. Diagnosis and treatment of coeliac disease reduce medical costs of care suggesting an economic advantage to earlier detection and treatment.
    Alimentary Pharmacology & Therapeutics 04/2010; 32(2):261-9. · 4.55 Impact Factor
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    ABSTRACT: 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. This study seeks to test the clinical utility of approaches for assessing forearm fracture risk. 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. 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). Detailed bone structure and strength measurements provide insight into forearm fracture pathogenesis, but femoral neck aBMD performs adequately for routine clinical risk assessment.
    Osteoporosis International 09/2009; 21(7):1161-9. · 4.04 Impact Factor
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    ABSTRACT: This analysis of National Health and Nutrition Examination Survey III data describes the prevalence of risk factors for osteoporosis and the proportions of men and postmenopausal women age 50 years and older who are candidates for treatment to lower fracture risk, according to the new FRAX-based National Osteoporosis Foundation Clinician's Guide. Little information is available on prevalence of osteoporosis risk factors or proportions of US men and women who are potential candidates for treatment. The prevalence of risk factors used in the new National Osteoporosis Foundation (NOF) FRAX-based Guide to the Prevention and Treatment of Osteoporosis was estimated using data from the third National Health and Nutrition Examination Survey (NHANES III). Risk factors not measured in NHANES III were simulated using World Health Organization cohorts. The proportion of US men and postmenopausal women age 50+ years who are treatment candidates by the new NOF Guide were calculated; for non-Hispanic white (NHW) women, the proportion eligible by the new NOF Guide was compared with that based on an earlier NOF Guide. Twenty percent of men and 37% of women were potential candidates for treatment to prevent fractures by the new NOF Guide. Among NHW women, 53% were potential candidates by the previous NOF Guide compared with 41% by the new guide. One fifth of men and 37% of postmenopausal women are eligible for osteoporosis treatment consideration by the new NOF Guide. However, fewer NHW women are eligible by the new guide than by the previous NOF Guide.
    Osteoporosis International 09/2009; 21(1):41-52. · 4.04 Impact Factor

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39k Citations
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Institutions

  • 1988–2012
    • Mayo Foundation for Medical Education and Research
      • • Division of Epidemiology
      • • Division of Rheumatology
      • • Mayo Medical School
      • • Department of Internal Medicine
      • • Department of Health Sciences Research
      • • Department of Anesthesiology
      • • Division of Gastroenterology and Hepatology
      • • Nicotine Dependence Center
      • • Department of Neurology
      Jacksonville, FL, United States
    • Oregon Health and Science University
      Portland, Oregon, United States
  • 1983–2012
    • Mayo Clinic - Rochester
      • • Department of Health Science Research
      • • Department of Laboratory Medicine & Pathology
      • • Department of Gastroenterology and Hepatology
      • • Department of Hospital Internal Medicine
      • • Department of Anesthesiology
      Rochester, Minnesota, United States
  • 2009–2011
    • Tufts University
      Georgia, United States
    • Kaiser Permanente
      Oakland, California, United States
  • 2007–2011
    • Centers for Disease Control and Prevention
      • National Center for Health Statistics
      Druid Hills, GA, United States
  • 2000–2007
    • Geisel School of Medicine at Dartmouth
      • Department of Medicine
      Hanover, New Hampshire, United States
  • 2002–2006
    • The University of Sheffield
      • Medical School
      Sheffield, England, United Kingdom
  • 2005
    • Belgian Scientific Institute for Public Health
      Bruxelles, Brussels Capital Region, Belgium
  • 2003
    • Nepean Hospital
      Sydney, New South Wales, Australia
  • 1997
    • Medical Technology and Practice Patterns Institute (MTPPI)
      Maryland, United States
  • 1994
    • University of Sydney
      Sydney, New South Wales, Australia
  • 1989–1993
    • Vanderbilt University
      • Department of Preventive Medicine
      Nashville, MI, United States
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
  • 1992
    • University of California, San Francisco
      • Department of Epidemiology and Biostatistics
      San Francisco, CA, United States
  • 1991
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
  • 1990
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
  • 1982–1984
    • University of Minnesota Rochester
      Rochester, Minnesota, United States