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We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause.We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006.Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk.Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.

Although fractures in both the pediatric and, especially, the elderly populations have been extensively investigated, comparatively little attention has been given to the age group in between. Thus, we used the comprehensive (inpatient and outpatient) data resources of the Rochester Epidemiology Project to determine incidence rates for all fractures among young adult (age range, 18 to 49 years) residents of Olmsted County, Minnesota, in 2009 to 2011, and compared the distribution of fracture sites and causes in this young adult cohort with those for older residents aged 50 years or older. During the 3-year study period, 2482 Olmsted County residents aged 18 to 49 years experienced 1 or more fractures. There were 1730 fractures among 1447 men compared with 1164 among 1035 women, and the age-adjusted incidence of all fractures was 66% greater among the men (1882 [95% confidence interval 1793-1971] versus 1135 [95% CI 1069-1201] per 100,000 person-years; p

Objective.Women and men with rheumatoid arthritis (RA) have an increased risk for fragility fractures and cardiovascular disease (CVD), each of which has been reported to contribute to excess morbidity and mortality in these patients. Fragility fractures share similar risk factors for CVD but may occur at relatively younger ages in patients with RA. We aimed to determine whether a fragility fracture predicts the development of CVD in women and men with RA.Methods.We studied a population-based cohort with incident RA from 1955 to 2007 and compared it with age- and sex-matched non-RA subjects. We identified fragility fractures and CVD events following the RA incidence/index date, along with relevant risk factors. We used Cox models to examine the association between fractures and the development of CVD, in which fractures and CVD risk factors were modeled as time-dependent covariates.Results.There were 1171 subjects (822 women; 349 men) in each of the RA and non-RA cohorts. Over followup, there were 406 and 346 fragility fractures and 286 and 225 CVD events, respectively. The overall CVD risk was increased significantly for RA subjects following a fragility fracture (HR 1.81, 95% CI 1.38–2.37) but not for non-RA subjects (HR 1.18, 95% CI 0.85–1.63). Results were similar for women and men with RA.Conclusion.Fragility fractures in both women and men with RA are associated with an increased risk for CVD events and should raise an alert to clinicians to target these individuals for further screening and preventive strategies for CVD.

Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population.Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA.In 1980-1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000-2007 (P0.001). Incidence increased with age (P0.001); however, the temporal increase was greater in younger people (P0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59-0.66) and women (HR 0.68; 95% CI, 0.58-0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04-1.57) and systemic (OR 1.83; 95% CI, 1.20-2.80) complications. Survival after diverticulitis was lower in older people (P0.001) and men (P0.001) and worsened over time (P0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007.The incidence of diverticulitis has increased by 50% in 2000-2007 compared with 1990-1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

Numerous studies have examined the association of body composition with bone development in children and adolescents, but none have used micro-finite element (μFE) analysis of high-resolution peripheral quantitative computed tomography images to assess bone strength.This study sought to examine the relations of appendicular lean mass (ALM) and total body fat mass (TBFM) to bone strength (failure load) at the distal radius and tibia.This was a cross-sectional study of 198 healthy 8- to15-year-old boys (n = 109) and girls (n = 89) performed in a Clinical Research Unit.After adjusting for bone age, height, fracture history, ALM, and TBFM, multiple linear regression analyses in boys and girls, separately, showed robust positive associations between ALM and failure loads at both the distal radius (boys: β = 0.92, P.001; girls: β = 0.66, P = .001) and tibia (boys: β = 0.96, P.001; girls: β = 0.66, P.001). By contrast, in both boys and girls the relationship between TBFM and failure load at the distal radius was virtually nonexistent (boys: β = -0.07; P = .284; girls: β = -0.03; P = .729). At the distal tibia, positive, albeit weak, associations were observed between TBFM and failure load in both boys (β = 0.09, P = .075) and girls (β = 0.17, P = .033).Our data highlight the importance of lean mass for optimizing bone strength during growth, and suggest that fat mass may have differential relations to bone strength at weight-bearing vs non-weight-bearing sites in children and adolescents. These observations suggest that the strength of the distal radius does not commensurately increase with excess gains in adiposity during growth, which may result in a mismatch between bone strength and the load experienced by the distal forearm during a fall. These findings may explain, in part, why obese children are over-represented among distal forearm fracture cases.

Children and adolescents who sustain a distal forearm fracture (DFF) owing to mild, but not moderate, trauma have reduced bone strength and cortical thinning at the distal radius and tibia. Whether these skeletal deficits track into adulthood is unknown. Therefore, we studied 75 women and 75 men (age range, 20 to 40 years) with a childhood (age < 18 years) DFF and 150 sex-matched controls with no history of fracture using high-resolution peripheral quantitative computed tomography (HRpQCT) to examine bone strength (ie, failure load) by micro-finite element (µFE) analysis, as well as cortical and trabecular bone parameters at the distal radius and tibia. Level of trauma (mild versus moderate) was assigned using a validated classification scheme, blind to imaging results. When compared to sex-matched, nonfracture controls, women and men with a mild trauma childhood DFF (eg, fall from standing height) had significant reductions in failure load (p < 0.05) of the distal radius, whereas women and men with a moderate trauma childhood DFF (eg, fall while riding a bicycle) had values similar to controls. Consistent findings were observed at the distal tibia. Furthermore, women and men with a mild trauma childhood DFF had significant deficits in distal radius cortical area (p < 0.05), and significantly lower dual-energy X-ray absorptiometry (DXA)-derived bone density at the radius, hip, and total body regions compared to controls (all p < 0.05). By contrast, women and men with a moderate trauma childhood DFF had bone density, structure, and strength that did not differ significantly from controls. These findings in young adults are consistent with our observations in children/adolescents with DFF, and they suggest that a mild trauma childhood DFF may presage suboptimal peak bone density, structure, and strength in young adulthood. Children and adolescents who suffer mild trauma DFFs may need to be targeted for lifestyle interventions to help achieve improved skeletal health.

To determine the extent to which excess mortality after fractures attributable to particular causes at specific skeletal sites can be predicted using data about all medical diagnoses, we conducted a historical cohort study among 1991 Olmsted County, Minnesota, residents aged ≥ 50 years who experienced any fracture in 1989 to 1991 and who were followed passively for up to 22 years for death from any cause. We used a machine learning approach, gradient boosting machine (GBM) modeling, to determine whether the comorbid conditions present at the time of fracture and those that arose subsequently could, in aggregate, identify patients at the greatest increased risk of death. During 21,867 person-years of follow-up, 1245 deaths were observed when 1061 were expected (standardized mortality ratio, 1.2; 95% confidence interval [CI] 1.1-1.2). Patients presented with a median history of 26 comorbid conditions each as assessed by the Clinical Classification Software system and 57 each over the total duration of follow-up. Using all available information, the excess deaths could be predicted with good accuracy (c-index ≥ 0.80) in 89% of the GBM models built for patients with different types of fracture; in one-third of the models, the c-index was ≥ 0.90. The conditions most prominent in the GBM prediction models were also reflected in the specific causes of death that were elevated, suggesting the influence of confounding on the relationship. However, the predominant comorbid conditions were mainly those responsible for mortality in the general population, rather than the specific diseases most closely associated with secondary osteoporosis. To reduce long-term deaths in the fracture population as a whole, a more general approach to the fracture patient is indicated.

Active cancer is the major predictor of venous thromboembolism (VTE) recurrence, but further stratification of recurrence risk is uncertain. In a population-based cohort study of all Olmsted County, Minnesota, residents with active cancer-related incident VTE during the 35-year period from 1966 to 2000 who survived 1 day or longer, we estimated VTE recurrence, bleeding on anticoagulant therapy, and survival and tested cancer and noncancer characteristics and secondary prophylaxis as predictors of VTE recurrence and bleeding, using Cox proportional hazards modeling. Of 477 patients, 139 developed recurrent VTE over the course of 1533 person-years of follow-up. The adjusted 10-year cumulative VTE recurrence rate was 28.6%. The adjusted 90-day cumulative incidence of major bleeding on anticoagulation was 1.9%. Survival was significantly worse for patients with cancer who had recurrent VTE (particularly pulmonary embolism) and with bleeding on anticoagulation. In a multivariable model, brain, lung, and ovarian cancer; myeloproliferative or myelodysplastic disorders; stage IV pancreatic cancer; other stage IV cancer; cancer stage progression; and leg paresis were associated with an increased hazard, and warfarin therapy was associated with a reduced hazard, of recurrent VTE. Recurrence rates were significantly higher for cancer patients with 1 or more vs no predictors of recurrence, suggesting these predictors may be useful for stratifying recurrence risk.

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high-resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10-year fracture probability using the country-specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age-matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact-appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact-appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures.

Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone "quality"). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50-80 years) including 30 patients diagnosed with T2D for >10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (-11.7%; p

Although distal forearm fractures (DFFs) are common during childhood and adolescence, it is unclear whether they reflect underlying skeletal deficits or are simply a consequence of the usual physical activities, and associated trauma, during growth. Therefore, we examined whether a recent DFF, resulting from mild or moderate trauma, is related to deficits in bone strength and cortical and trabecular bone macro- and microstructure compared with nonfracture controls. High-resolution peripheral quantitative computed tomography was used to assess micro-finite element-derived bone strength (ie, failure load) and to measure cortical and trabecular bone parameters at the distal radius and tibia in 115 boys and girls with a recent (

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, MN, USA, residents in 2009 to 2011 compared with similar data from 1989 to 1991. During the 3-year study period, 2009 to 2011, 3549 residents ≥50 years of age experienced 5244 separate fractures. The age- and sex-adjusted (to the 2010 US white population) incidence of any fracture was 2704 per 100,000 person-years (95% confidence interval [CI] 2614 to 2793) and that for all fractures was 4017 per 100,000 (95% CI 3908 to 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 to 1991 and 2009 to 2011. This was mainly attributable 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 aged 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. © 2014 American Society for Bone and Mineral Research.

The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio. Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index. Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm3, respectively; P

Introduction: We assessed proficiency (accuracy and intra- and intertest reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic sensorimotor polyneuropathy (DSPN). Methods: Technologists from 3 medical centers using different but identical QSTs independently assessed 6 modalities of sensation of the foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. Results: Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intraclass correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra- or intertest differences were observed. Conclusions: These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra- or intertest differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length-dependent sensorimotor polyneuropathies. Muscle Nerve 49: 645–653, 2014

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

More accurate techniques to estimate fracture risk could help reduce the burden of fractures in postmenopausal women. Although micro-finite element (µFE) simulations allow a direct assessment of bone mechanical performance, in this first clinical study we investigated whether the additional information obtained using geometrically and materially nonlinear µFE simulations allows a better discrimination between fracture cases and controls. We used patient data and high-resolution peripheral quantitative computed tomography (HRpQCT) measurements from our previous clinical study on fracture risk, which compared 100 postmenopausal women with a distal forearm fracture to 105 controls. Analyzing these data with the nonlinear µFE simulations, the odds ratio (OR) for the factor-of-risk (yield load divided by the expected fall load) was marginally higher (1.99; 95% confidence interval [CI], 1.41–2.77) than for the factor-of-risk computed from linear µFE (1.89; 95% CI, 1.37–2.69). The yield load and the energy absorbed up to the yield point as computed from nonlinear µFE were highly correlated with the initial stiffness (R2 = 0.97 and 0.94, respectively) and could therefore be derived from linear simulations with little loss in precision. However, yield deformation was not related to any other measurement performed and was itself a good predictor of fracture risk (OR, 1.89; 95% CI, 1.39–2.63). Moreover, a combined risk score integrating information on relative bone strength (yield load-based factor-of-risk), bone ductility (yield deformation), and the structural integrity of the bone under critical loads (cortical plastic volume) improved the separation of cases and controls by one-third (OR, 2.66; 95% CI, 1.84–4.02). We therefore conclude that nonlinear µFE simulations provide important additional information on the risk of distal forearm fractures not accessible from linear µFE nor from other techniques assessing bone microstructure, density, or mass. © 2013 American Society for Bone and Mineral Research.

Objective.Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA and whether such risk occurs early in the disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.Methods.We studied a population-based inception cohort with RA from Olmsted County, Minnesota, USA. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.Results.The hazard ratio (HR; 95% CI) for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 (1.36–1.96) for women and 1.40 (1.02–1.93) for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years [HR, 1.43 (1.16–1.77) and 1.34 (0.92–1.94), respectively], or at age < 50 years [HR, 2.34 (1.61–3.42) and 1.74 (0.91–3.30), respectively]. However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR, 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).Conclusion.Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.

Distal forearm fractures are among the most common fractures during childhood, but it remains unclear whether they predict an increased fracture risk later in life. We studied a population-based cohort of 1776 children ≤18 years of age, from Olmsted County, MN, USA, who had a distal forearm fracture in 1935–1992. Incident fractures occurring at age ≥35 years were identified through review of complete medical records using the linkage system of the Rochester Epidemiology Project. Observed nonpathologic fractures resulting from no more than moderate trauma (fragility fractures) were compared with expected numbers estimated from fracture site–specific incidence rates, based on age, sex, and calendar year, for Olmsted County (standardized incidence ratios [SIR]). In 1086 boys (mean ± SD age; 11 ± 4 years) and 690 girls (10 ± 4 years) followed for 27,292 person-years after the age of 35 years, subsequent fragility fractures were observed in 144 (13%) men and 74 (11%) women. There was an increased risk for future fragility fractures in boys who had a distal forearm fracture (SIR, 1.9; 95% CI, 1.6–2.3) but not girls (SIR, 1.0; 95% CI, 0.8–1.2). Fragility fractures at both major osteoporotic (hip, spine, wrist, and shoulder) sites (SIR, 2.6; 95% CI, 2.1–3.3) and remaining sites (SIR, 1.7; 95% CI, 1.3–2.0) were increased in men, irrespective of age at distal forearm fracture as boys. A distal forearm fracture in boys, but not girls, is associated with an increased risk for fragility fractures as older adults. It is necessary to determine whether the increased fractures observed in men is due to persistent deficits of bone strength, continued high fracture risk activity, or both. Until then, men should be asked about a childhood distal forearm fracture and, if so, warrant further screening and counseling on measures to optimize bone health and prevent fractures.

Assessment of signs, symptoms, functional impairments, and nerve tests are the the main clinical measures used for diagnosing and characterizing peripheral nerve disease. Among tests, nerve conduction (NC) has increasingly been advocated for objective electrodiagnosis and characterization of focal, multifocal, or generalized polyneuropathies.1–4 NC is also being used for conducting epidemiological surveys5–7 and therapeutic trials.8,9 For the latter purposes, NC has gained consensus approval,10–13 because its results are considered sensitive, objective, quantitative, and reproducible indications of nerve dysfunction that correlate with clinical signs and symptoms and with neurophysiological and neuropathological abnormalities.14,15 In knowing that assessment of attributes of NC can provide sensitive and quantitative diagnostic and characterizing information about diabetic sensorimotor polyneuropathy (DSPN) for use in medical practice and therapeutic trials, it would also be helpful to learn how accurately and reproducibly within and among clinical neurophysiologists this assessment is done (proficiency). There is already considerable information about test–retest reproducibility of individual attributes of NC focusing mainly on which attributes show the greatest reproducibility and, with this criterion, are suitable for therapeutic trials (albeit test–retest reproducibility is only 1 criterion for such selection). Reproducibility studies have not addressed the issue of proficiency—that is, the variability of NC results among different clinical neurophysiologists without retraining, consensus development, or quality control of their evaluations. Two previous studies have assessed intra- and interobserver variability of measured attributes of NC. In the first study, electromyographers from 1 medical center studied healthy subjects,16 and in a second they studied patients with diabetes mellitus (DM).17 They found no significant intraobserver differences, but significant interobserver differences. They concluded that, for therapeutic trials, it may be advisable to have the same electromyographers perform the sequential NCs over time on patients in the trial. The present trial, Clinical vs. Neurophysiology Trial 3 (Cl vs. NPhys Trial 3) had each group of clinical neurophysiologists and their associate technologist perform NC assessment of 8 attributes of NC of the leg of 24 masked patients with DM without and with DSPN on consecutive days. The expert clinical neurophysiologists were asked to make independent measurements of the attributes without any clinical information, record whether their values were normal or abnormal, and finally make a judgment of whether the abnormalities were diagnostic of DSPN. Thus, these studies specifically addressed 3 questions: (1) Did expert neurophysiologists obtain the same measured values of the 8 attributes of NC without intra- or interobserver differences? (2) Assuming that they did, did they judge abnormality of attributes without intraor interobserver differences? (3) Did they judge DSPN as present or not without intra- or interobserver differences? It was recognized prior to the study that if the first question could not be answered affirmatively, it may not be possible to adequately assess questions (2) and (3). This trial also addresses the broader question of whether further standardization of NC assessment is needed and possible, or whether it is really necessary to have the same electromyographer perform serial evaluations of individual patients. This trial is part of a series of studies organized by Cl vs. NPhys Trial investigators to assess the proficiency of assessment of signs, symptoms, and clinical diagnosis,18,19 attributes of NC (the present Trial 3) and other nerve tests for the diagnosis and characterization of polyneuropathies, especially DSPN. The overall goal is to improve the quality of these evaluations of measures of polyneuropathy in medical practice, medical education, and the conduct of therapeutic trials.

Aging is associated with worsening bone structure and increasing risk of hip fracture. However, the commonly used clinical tool, dual-energy x-ray absorptiometry, does not provide information on changes with age or disease separately in trabecular versus cortical bone or in bone geometry. Here we used 3D quantitative computed tomography (QCT) to analyze age-related changes in femoral volumetric bone mineral density (vBMD) and structure in a well characterized, population-based cohort of Rochester, Minnesota women.MIAF-Femur (MIAF: medical image analysis framework) was used for the analysis of CT datasets from 358 women age 20 to 97 years. Integral, "apparent" cortical (rather than true cortical vBMD, due to volume averaging effects) and trabecular vBMD, volume, and bone mineral content (BMC) as well as cortical thickness of the femur head, neck, trochanter, inter-trochanteric, and proximal shaft volumes of interest (VOIs) were measured. In addition, changes in vBMD in the superior, inferior, posterior and anterior quadrants of the femur neck were assessed.Cross-sectional percent decreases in vBMD across life were 2- to 5-fold higher in trabecular versus cortical bone at all sites in the femur, although absolute changes in the trabecular and cortical bone were fairly similar. In addition, the slopes of the relationships of trabecular vBMD with age were generally similar in pre- and postmenopausal women, whereas apparent cortical vBMD in the femur neck, trochanter, inter-trochanteric region, and proximal shaft remained relatively stable in premenopausal women but decreased significantly with age following the menopause. Bone volume increased at all sites, more so in pre- compared to postmenopausal women. Age-related BMC changes were not significant in premenopausal women, but BMC losses were highly significant in postmenopausal women. Detailed analyses of femur neck cortical bone showed that percent apparent vBMD decreases in the superior quadrants were 2- to 3-fold greater than in the inferior quadrants; changes in absolute values were most different (~2-fold) between the superior-posterior and inferior-posterior quadrants.These data demonstrate that patterns of changes with age within the femur differ in the trabecular versus cortical bone. In the cortical compartment which, due to limitations in spatial resolution, contains some subcortical bone and should be regarded as an "apparent" cortical VOI, the superior quadrants in the femur neck undergo the greatest decreases. These findings may have important implications for understanding the structural basis for increased hip fracture risk with aging.

Objective To describe the prevalence of nonacute conditions among patients seeking health care in a defined US population, emphasizing age, sex, and ethnic differences. Patients and Methods The Rochester Epidemiology Project (REP) medical records linkage system was used to identify all residents of Olmsted County, Minnesota, on April 1, 2009, who had consented to review of their medical records for research (142,377 patients). We then electronically extracted all International Classification of Diseases, Ninth Revision codes noted in the records of these patients by any health care institution between January 1, 2005, and December 31, 2009. We grouped International Classification of Diseases, Ninth Revision codes into clinical classification codes and then into 47 broader disease groups associated with health-related quality of life. Age- and sex-specific prevalence was estimated by dividing the number of individuals within each group by the corresponding age- and sex-specific population. Patients within a group who had multiple codes were counted only once. Results We included a total of 142,377 patients, 75,512 (53%) of whom were female. Skin disorders (42.7%), osteoarthritis and joint disorders (33.6%), back problems (23.9%), disorders of lipid metabolism (22.4%), and upper respiratory tract disease (22.1%, excluding asthma) were the most prevalent disease groups in this population. Ten of the 15 most prevalent disease groups were more common in women in almost all age groups, whereas disorders of lipid metabolism, hypertension, and diabetes were more common in men. Additionally, the prevalence of 7 of the 10 most common groups increased with advancing age. Prevalence also varied across ethnic groups (whites, blacks, and Asians). Conclusion Our findings suggest areas for focused research that may lead to better health care delivery and improved population health.

The Rochester Epidemiology Project (REP) has maintained a comprehensive medical records linkage system for nearly half a century for almost all persons residing in Olmsted County, Minnesota. Herein, we provide a brief history of the REP before and after 1966, the year in which the REP was officially established. The key protagonists before 1966 were Henry Plummer, Mabel Root, and Joseph Berkson, who developed a medical records linkage system at Mayo Clinic. In 1966, Leonard Kurland established collaborative agreements with other local health care providers (hospitals, physician groups, and clinics [primarily Olmsted Medical Center]) to develop a medical records linkage system that covered the entire population of Olmsted County, and he obtained funding from the National Institutes of Health to support the new system. In 1997, L. Joseph Melton III addressed emerging concerns about the confidentiality of medical record information by introducing a broad patient research authorization as per Minnesota state law. We describe how the key protagonists of the REP have responded to challenges posed by evolving medical knowledge, information technology, and public expectation and policy. In addition, we provide a general description of the system; discuss issues of data quality, reliability, and validity; describe the research team structure; provide information about funding; and compare the REP with other medical information systems. The REP can serve as a model for the development of similar research infrastructures in the United States and worldwide.

BACKGROUND The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.

Thiazide diuretics, the antihypertensive agent prescribed most frequently worldwide, are commonly associated with hypercalcemia. However, the epidemiology and clinical features are poorly understood.To update the incidence of thiazide-associated hypercalcemia and clarify its clinical features.In a population-based descriptive study, Olmsted County, Minnesota, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System from 2002-2010 and were added to the historical cohort beginning in 1992.Incidence rates were adjusted to the 2010 United States white population.Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100,000, compared to an overall rate of 12 per 100,000 in 1992-2010. Severe hypercalcemia was not observed in the cohort despite continuation of thiazide treatment in 62.4%. Of patients discontinuing thiazides, 71% continued to have hypercalcemia. Primary hyperparathyroidism was diagnosed in 53 patients (24%), including five patients who underwent parathyroidectomy without thiazide discontinuation.Many patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism. Additionally, a sharp rise in thiazide-associated hypercalcemia incidence began in 1998, paralleling the increase observed in primary hyperparathyroidism in this community. Case ascertainment bias from targeted osteoporosis screening is the most likely explanation.

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.

The Rochester Epidemiology Project (REP) medical records-linkage system was established in 1966 to capture health care information for the entire population of Olmsted County, MN, USA. The REP includes a dynamic cohort of 502 820 unique individuals who resided in Olmsted County at some point between 1966 and 2010, and received health care for any reason at a health care provider within the system. The data available electronically (electronic REP indexes) include demographic characteristics, medical diagnostic codes, surgical procedure codes and death information (including causes of death). In addition, for each resident, the system keeps a complete list of all paper records, electronic records and scanned documents that are available in full text for in-depth review and abstraction. The REP serves as the research infrastructure for studies of virtually all diseases that come to medical attention, and has supported over 2000 peer-reviewed publications since 1966. The system covers residents of all ages and both sexes, regardless of socio-economic status, ethnicity or insurance status. For further information regarding the use of the REP for a specific study, please visit our website at www.rochesterproject.org or contact us at info@rochesterproject.org. Our website also provides access to an introductory video in English and Spanish.

Context: Studies in rodents have demonstrated that sympathetic activity reduces bone formation and bone mass; these effects are mediated by the noncollagenous matrix protein, osteopontin. Objective: The objective of the study was to relate sympathetic activity (measured using microneurography at the peroneal nerve) to bone microstructure (assessed by high resolution peripheral quantitative computed tomography), bone turnover, and plasma osteopontin levels. Design, Setting, and Patients: Twenty-three women aged 20–72 yr (10 premenopausal and 13 postmenopausal) were studied in the Clinical Research Unit. Results: Sympathetic activity (bursts per 100 heart beats) was 2.4-fold higher in postmenopausal as compared with premenopausal women (P < 0.001). In the two groups combined and after age adjustment, sympathetic activity was inversely correlated with trabecular bone volume fraction (r = −0.55, P < 0.01) and thickness (r = −0.59, P < 0.01) and positively correlated with trabecular separation (r = 0.45, P < 0...

Objectives: To quantify the occurrence of myocardial infarction (MI) occurring in the early postoperative period after surgical hip fracture repair and estimate the effect on 1-year mortality. Design: A population-based, historical cohort study of individuals who underwent surgical repair of a hip fracture that used the computerized medical record linkage system of the Rochester Epidemiology Project. Setting: Academic and community hospitals, outpatient offices, and nursing homes in Olmsted County, Minnesota. Participants: Over the 15-year study period (1988�2002), 1,116 elderly adults underwent surgical repair of a hip fracture. Measurements: At the end of the first 7 days after hip fracture repair, participants were classified into one of three groups: clinically verified MI (cv-MI), subclinical myocardial ischemia, and no myocardial ischemia. One-year mortality was compared between these groups. Multivariate models assessed risk factors for early postoperative cv-MI and 1-year mortality. Results: Within the first 7 days after hip fracture repair, 116 (10.4%) participants experienced cv-MI and 41 (3.7%) subclinical myocardial ischemia. Overall 1-year mortality was 22%, with no difference between those with subclinical myocardial ischemia and those with no myocardial ischemia. One-year mortality for those with cv-MI (35.8%) was significantly higher than for the other two groups. Occurrence of early postoperative cv-MI, male sex, and history of heart failure or dementia were independently associated with greater 1-year mortality, whereas prefracture home residence and preoperative higher hemoglobin were protective. Conclusion: Rates of early postoperative, cv-MI after hip fracture repair exceed rates after other major orthopedic surgeries and are independently associated with greater 1-year mortality.

Skeletal muscle and bone form highly-integrated systems that undergo significant age-related changes, but the relationships between muscle mass and trabecular versus cortical bone or trabecular microarchitecture have not been systematically investigated. Thus, we examined the association between appendicular skeletal muscle mass (ASM) relative to height squared (relative ASM) and bone parameters at several sites assessed by conventional as well as high-resolution peripheral QCT in a cohort of 272 women and 317 men aged 20 to 97 years. In women, relative ASM was associated with cortical thickness (CtTh) at the femoral neck, lumbar spine, radius, and tibia (age-and physical activity adjusted r = 0.19–0.32; all p

The anal sphincters and pelvic floor muscles preserve fecal continence and participate in defecation (1). By visualizing structural (e.g., rectocele) and functional (e.g., impaired anal relaxation) disturbances, barium defecography and magnetic resonance imaging (MRI) facilitate the diagnosis of defecatory disorders, particularly when anal manometry and a rectal balloon expulsion test are inconclusive (2-6). MRI also reveals puborectalis atrophy and impaired pelvic floor contraction in some women with fecal incontinence (FI) (7-9). However, the clinical utility of barium defecography and MRI is limited by variable reproducibility of these assessments. For example, in one study, inter-observer agreement was good for identifying enteroceles and rectoceles but suboptimal for identifying intussusception, anismus, or the puborectalis impression by barium defecography (10). Moreover, for some measurements, agreement was much better for experienced observers (10). The American Gastroenterological Association technical review concluded that “there is poor agreement between independent observers in the measurement of the anorectal angle, a parameter thought to be critical to the interpretation of defecography results” (11). This is partly attributable to lack of a standardized definition for the rectal axis, which forms one aspect of the anorectal angle and can be drawn through the anterior, middle or posterior rectal wall. Moreover, the rectum is curvilinear, and the puborectalis indentation on the posterior rectal wall is variable. Hence, even minor differences in the orientation of the rectal axis can profoundly affect the anorectal angle. Lastly, the bony landmarks (e.g., pubic symphysis, coccyx) which are used to measure perineal descent may not be visible during barium defecography but are distinctly visualized on MR images (12). Nonetheless, and despite centralized training, a NIH-sponsored multi-institutional study concluded that “measurement variability adversely affects the utility of many MRI measurements for multicenter pelvic floor disorder research,” although agreement was better for bony than pelvic soft-tissue measurements during dynamic pelvic MRI (13). By contrast, we documented substantial inter-observer agreement for anorectal angles and the anorectal location at rest, during squeeze and evacuation measured by MRI in asymptomatic women and women with defecatory disorders; however, differences between observers were statistically significant (12). While most attention has focused on anorectal motion and the puborectalis, the coccyx also moves during pelvic floor contraction and rectal evacuation (14). The coccygei, which have a variable proportion of muscle and fibrous tissue, may pull forward and support the coccyx, after it has been pressed backwards, during defecation or parturition (14-16). With the levatores ani and piriforms, they close the posterior part of the pelvic outlet. Previous studies have evaluated the relationship of coccygeal mobility to age, sex, parity, and minor trauma but not to fecal incontinence. It is conceivable that coccygeal weakness may contribute to pelvic weakness in FI. Hence, the aims of this study were to (i) to develop a user-friendly semi-automated program to measure anorectal motion by defecography; (ii) evaluate the within-subject reproducibility of anorectal motion measured by this semi-automated program; (iii) to compare measurements of anorectal motion by a radiologist and a semi-automated program; and (iv) compare anorectal motion disturbances in women with and without FI. A more robust and refined approach to measure pelvic floor motion by MR defecography may enhance the utility of this technique in clinical practice and research studies.

Current concepts based on referral center data suggest that pelvic floor injury from obstetric trauma is a major risk factor for fecal incontinence (FI) in women. In contrast, a majority of community women only develop FI decades after vaginal delivery, and obstetric events are not independent risk factors for FI. However, obstetric events are imperfect surrogates for anal and pelvic floor injury, which is often clinically occult. Hence, the objectives of this study were to evaluate the relationship between prior obstetric events, pelvic floor injury, and FI among community women.In this nested case-control study of 68 women with FI (cases; mean age 57 years) and 68 age-matched controls from a population-based cohort in Olmsted County, MN, pelvic floor anatomy and motion during voluntary contraction and defecation were assessed by magnetic resonance imaging. Obstetric events and bowel habits were recorded.By multivariable analysis, internal sphincter injury (cases-28%, controls-6%; odds ratio (OR): 8.8; 95% confidence interval (CI): 2.3-34) and reduced perineal descent during defecation (cases-2.6 ± 0.2 cm, controls-3.1 ± 0.2 cm; OR: 1.7; 95% CI: 1.2-2.4) increased FI risk, but external sphincter injury (cases-25%, controls-4%; P0.005) was not independently predictive. Puborectalis injury was associated (P0.05) with impaired anorectal motion during squeeze, but was not independently associated with FI. Grades 3-4 episiotomy (OR: 3.9; 95% CI: 1.4-11) but not other obstetric events increased the risk for pelvic floor injury. Heavy smoking (≥ 20 pack-years) was associated (P=0.052) with external sphincter atrophy.State-of-the-art imaging techniques reveal pelvic floor injury or abnormal anorectal motion in a minority of community women with FI. Internal sphincter injury and reduced perineal descent during defecation are independent risk factors for FI. In addition to grades 3-4 episiotomy, smoking may be a potentially preventable, risk factor for pelvic floor injury.

A positive association has been reported between greater bone density and higher breast cancer risk, suggesting that these women could be at reduced risk of fracture. To estimate fracture risk among unselected community women with breast cancer and to systematically assess associations with various risk factors including breast cancer treatments, we conducted a population-based historical cohort study of 608 Olmsted County, MN, USA, women with invasive breast cancer first diagnosed in 1990 to 1999 (mean age 61.6 ± 14.8 years), who were followed for 5776 person-years. Altogether, 568 fractures were observed in 270 women (98 per 1000 person-years). Overall fracture risk was elevated 1.8-fold, but the absolute increase in risk was only 9%, and 56% of the women did not experience a fracture during follow-up. Excluding pathologic fractures (15%) and those found incidentally (24%), to allow for ascertainment bias, the standardized incidence ratio was 1.2 (95% confidence interval [CI] 0.99 to 1.3) for total fracture risk and 0.9 (95% CI 0.7 to 1.2) for osteoporotic fracture risk alone. Various breast cancer treatments were associated with an increased risk of fracture, but those associations were strongest for pathologic fractures, which were relatively more common among the women who were premenopausal when their breast cancer was diagnosed. Moreover, underlying clinical characteristics prompting different treatments may have been partially responsible for the associated fracture outcomes (indication bias). These data thus demonstrate that breast cancer patients in general are not at greatly increased risk of fracture but neither are they protected from fractures despite any determinants that breast cancer and high bone density may have in common.

Previous studies using dual-energy X-ray absorptiometry (DXA) have demonstrated that age is a major predictor of bone fragility and fracture risk independent of areal bone mineral density (aBMD). Although this aBMD-independent effect of age has been attributed to poor bone "quality," the structural basis for this remains unclear. Because high-resolution peripheral quantitative computed tomography (HRpQCT) can assess bone microarchitecture, we matched younger and older subjects for aBMD at the ultradistal radius and assessed for possible differences in trabecular or cortical microstructure by HRpQCT. From an age-stratified, random sample of community adults, 44 women aged

OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

Background: Increasing colorectal cancer screening (CRCS) is important for attaining the Healthy People 2020 goal of reducing CRC-related morbidity and mortality. Evaluating CRCS trends can help identify shifts in CRCS, and specific groups that might be targeted for CRCS. Methods: We utilized medical records to describe population-based adherence to average-risk CRCS guidelines from 1997 to 2008 in Olmsted County, MN. CRCS trends were analyzed overall and by gender, age, and adherence to screening mammography (women only). We also carried out an analysis to examine whether CRCS is being initiated at the recommended age of 50. Results: From 1997 to 2008, the size of the total eligible sample ranged from 20,585 to 21,468 people. CRCS increased from 22% to 65% for women and from 17% to 59% for men (P < 0.001 for both) between 1997 and 2008. CRCS among women current with mammography screening increased from 26% to 74%, and this group was more likely to be adherent to CRCS than all other subgroups analyzed (P < 0.001).The mean ages of screening initiation were stable throughout the study period, with a mean age of 55 years among both men and women in 2008. Conclusion: Although overall CRCS tripled during the study period, there is still room for improvement. Impact: Working to decrease the age at first screening, exploration of gender differences in screening behavior, and targeting women adherent to mammography but not to CRCS seem warranted. Cancer Epidemiol Biomarkers Prev; 21(2); 347–50. ©2011 AACR.

To illustrate the problem of generalizability of epidemiological findings derived from a single population using data from the Rochester Epidemiology Project and from the US Census.We compared the characteristics of the Olmsted County, Minnesota, population with the characteristics of populations residing in the state of Minnesota, the Upper Midwest, and the entire United States.Age, sex, and ethnic characteristics of Olmsted County were similar to those of the state of Minnesota and the Upper Midwest from 1970 to 2000. However, Olmsted County was less ethnically diverse than the entire US population (90.3% vs 75.1% white), more highly educated (91.1% vs 80.4% high school graduates), and wealthier ($51,316 vs $41,994 median household income; 2000 US Census data). Age- and sex-specific mortality rates were similar for Olmsted County, the state of Minnesota, and the entire United States.We provide an example of analyses and comparisons that may guide the generalization of epidemiological findings from a single population to other populations or to the entire United States.

In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM.In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling.The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM.Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM.

Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.

There remains little consensus on the link between vitamin levels and muscle mass or strength. We therefore investigated the association of serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2) D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength. We studied 311 men (mean age, 56 years; range, 23-91 years) and 356 women (mean age, 57 years; range, 21-97 years) representing an age-stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual-energy X-ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)(2) D, and PTH quartiles, adjusted for age, physical activity, fat mass, and season. We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)(2) D levels and low skeletal mass in both men and women and low isometric knee extension moment in women, after adjustment for potential confounders. Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)(2) D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration.

Hip fracture and heart failure are becoming more prevalent conditions in hospitalized patients. Despite differences in postoperative outcomes from other intermediate risk procedures, guidelines classify hip fracture repair as an intermediate risk operation.This population-based study sought to examine the prevalence and incidence of heart failure in hip fracture patients.We conducted a population-based historical cohort study of 1116 Olmsted County, MN residents undergoing 1212 hip surgeries from 1988 through 2002. Data were obtained through medical record review. Heart failure was defined by Framingham criteria.The prevalence of preoperative heart failure in our study population was 27% (327 of 1212 cases). Those with preoperative heart failure demonstrated longer lengths of stay, were more often discharged to a skilled facility, and had higher inpatient mortality rates. Rates of postoperative heart failure were 6.7% at seven days and 21.3% at one year. Postoperative heart failure was more common among those with preoperative heart failure (HR 3.0), and those with preoperative heart failure demonstrated higher postoperative mortality rates. Men had a higher risk of postoperative mortality compared to women. Overall survival was lowest among those with both preoperative and postoperative heart failure.Heart failure represents a common and serious perioperative condition in hip fracture patients. Hip fracture patients with and without heart failure carry higher postoperative risk than guidelines may suggest. Future work must focus on the perioperative management of hip fracture patients with and without heart failure to mitigate postoperative morbidity.

To estimate the incidence of breast carcinoma and survival in patients younger than 25 years old, and to describe presenting clinical signs and symptoms of breast cancer in this age group.A population-based descriptive study and case review in Olmsted County, Minnesota, was conducted using the resources of the Rochester Epidemiology Project. Participants were Olmsted County girls and women younger than 25 years old with histopathologically confirmed breast carcinoma diagnosed between 1935 and 2005. Nonresidents who presented to a medical facility within Olmsted County during this time period were included in some portions of the analysis. Main outcome measures were age-adjusted incidence, 5-year survival, and clinical presentation of breast carcinoma in girls and women younger than 25 years of age.With four breast carcinomas observed in Olmsted County residents over 1,201,539 person-years, the annual age-adjusted incidence of breast cancer in this population was 3.2 per million (95% confidence interval, 0.1-6.2). All four cancers occurred in the 20- to 24-year age group (age-specific incidence, 16.2 per million). Eight additional cases of breast carcinoma were identified in nonresidents. Delay in diagnosis was common. All had at least one feature worrisome for an aggressive neoplasm identified in their clinical history, on physical examination or by imaging.Breast carcinoma in young women is very rare, associated with delayed diagnosis, and usually associated with concerning features requiring biopsy.III.

Recent studies in mice have demonstrated that osteocalcin (OCN) regulates testosterone (T) production in males but not in females. We hypothesized that this novel bone-testis axis may be most relevant during rapid skeletal growth to help maximize bone size. Thus we measured serum T, total and undercarboxylated (UC) OCN, and periosteal circumference at the radius in 56 boys (bone age 4 to 20 years). T was correlated with OCN (bone-age-adjusted r = 0.30, p = .024), with a similar trend for UC OCN. T began to increase in the boys at bone age 11 years, and OCN peaked at bone age 14 years. Thus we divided the boys into three groups: 4 to 10 years (n = 16), 11 to 14 years (n = 18), and 15 to 20 years (n = 22). In boys of bone age 11 to 14 years (but not the other two groups), OCN was correlated with T (r = 0.57, p = .013), with a similar trend for UC OCN; T, in turn, was correlated with periosteal circumference (r = 0.75, p

Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990-1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited.

Background— Data on the association between myocardial infarction (MI) and fractures are scarce. Recent changes in the epidemiology of MI justify exploring this relationship. We evaluated whether MI constitutes a risk factor for osteoporotic fracture and examined secular trends in this association. Methods and Results— Consecutive Olmsted County, Minnesota, residents with incident MI diagnosed in 1979 to 2006 and community control subjects individually matched (1:1) to cases on age, sex, and year of onset (n=6642) were followed up through 2009. Outcome measures were time to osteoporotic fracture, overall and by anatomic site, and death. Fracture incidence rates were stable in controls but increased markedly over time among MI cases. Accordingly, although an overall excess of fracture risk after MI was observed (adjusted hazard ratio, 1.32; 95% confidence interval, 1.12 to 1.56), substantial temporal variations were noted (1979 to 1989: hazard ratio, 0.81; 95% confidence interval, 0.58 to 1.12; 1990 to 1999: hazard ratio, 1.47; 95% confidence interval, 1.10 to 1.96; 2000 to 2006: hazard ratio, 1.73; 95% confidence interval, 1.32 to 2.27; P for trend Conclusions— Over the past decades, the association between MI and osteoporotic fractures increased steadily. The trend is consistent with the displacement of post-MI outcomes toward noncardiovascular events, highlighting the need for comprehensive prevention strategies to accommodate the changing epidemiology of MI.