Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation ...to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval CI, 0.97-0.99) for any fracture, 0.97 (95% CI, 0.96-0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91-0.94) for hip fracture (all p <0.001). The RR per unit change in BMI was very similar in men and women ( p >0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m(2), a BMI of 20 kg/m(2) was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71-2.22) for hip fracture. In contrast, a BMI of 30 kg/m(2), when compared with a BMI of 25 kg/m(2), was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69-0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.
There is increasing laboratory evidence for a neuroprotective effect of estrogen; however, the clinical and epidemiologic evidence remains limited and conflicting. We studied the association of ...oophorectomy performed before the onset of menopause with the risk of subsequent cognitive impairment or dementia.
We included all women who underwent unilateral or bilateral oophorectomy before the onset of menopause for a non-cancer indication while residing in Olmsted County, MN, from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 813 women with unilateral oophorectomy, 676 women with bilateral oophorectomy, and 1,472 referent women. Women were followed through death or end of study using either direct or proxy interviews.
Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of cognitive impairment or dementia compared to referent women (hazard ratio HR = 1.46; 95% CI 1.13 to 1.90; adjusted for education, type of interview, and history of depression). The risk increased with younger age at oophorectomy (test for linear trend; adjusted p < 0.0001). These associations were similar regardless of the indication for the oophorectomy, and for women who underwent unilateral or bilateral oophorectomy considered separately.
Both unilateral and bilateral oophorectomy preceding the onset of menopause are associated with an increased risk of cognitive impairment or dementia. The effect is age-dependent and suggests a critical age window for neuroprotection.
Summary The decline in hip fracture incidence is now accompanied by a further reduction in the likelihood of a recurrent hip fracture among survivors of the first fracture. Introduction Hip fracture ...incidence is declining in North America, but trends in hip fracture recurrence have not been described. Methods All hip fracture events among Olmsted County, Minnesota residents in 1980-2006 were identified. Secular trends were assessed using Poisson regression, and predictors of recurrence were evaluated with Andersen-Gill time-to-fracture regression models. Results Altogether, 2,752 hip fractures (median age, 83 years; 76% female) were observed, including 311 recurrences. Between 1980 and 2006, the incidence of a first-ever hip fracture declined by 1.37%/year for women (p < 0.001) and 0.06%/year for men (p = 0.917). Among 2,434 residents with a first-ever hip fracture, the cumulative incidence of a second hip fracture after 10 years was 11% in women and 6% in men with death treated as a competing risk. Age and calendar year of fracture were independently associated with hip fracture recurrence. Accounting for the reduction in first-ever hip fracture rates over time, hip fracture recurrence appeared to decline after 1997. Conclusion A recent reduction in hip fracture recurrence is somewhat greater than expected from the declining incidence of hip fractures generally. Additional research is needed to determine the extent to which this can be attributed to improved patient management.
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.
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.
This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During ...4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2-5.3) than women (SIR, 2.7; 95% CI, 2.4-3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11-14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8-2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01-2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip.
In a population‐based cross‐sectional study, we examined effects of sex and age on bone microstructure at the wrist using high‐resolution 3‐D pQCT. Compared with women, men had thicker trabeculae in ...young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age‐related increases in wrist fractures.
Introduction: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population‐based studies.
Materials and Methods: We used high‐resolution 3‐D pQCT imaging (voxel size, 89 μm) to define, in a random sample of women (n = 324) and men (n = 278) 21–97 years of age, sex and age effects on bone microstructure at the wrist.
Results: Relative to young women (age, 20–29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross‐sectional decreases in BV/TV were similar in women (−27%) and in men (−26%), but whereas women had significant decreases in TbN (−13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and −2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (−24%) than in women (−18%; p = 0.010 versus men).
Conclusions: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life‐long risk of fractures in men, and specifically, their virtual immunity to age‐related increases in distal forearm fractures.
There is increasing laboratory evidence for a neuroprotective effect of estrogen on the nigrostriatal pathway; however, the epidemiologic evidence remains limited and conflicting. We studied the ...association of oophorectomy performed before the onset of menopause with the risk of subsequent parkinsonism.
We included all women who underwent either unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987 while residing in Olmsted County, MN. Each member of the oophorectomy cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed through death or end of study using a combination of direct or proxy interviews, neurologic examinations, medical records in a records-linkage system, and death certificates.
Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with referent women (HR 1.68; 95% CI 1.06 to 2.67; p = 0.03), and the risk increased with younger age at oophorectomy (test for linear trend; p = 0.01). The findings were similar regardless of the indication for the oophorectomy, and for unilateral or bilateral oophorectomy considered separately. The findings were also consistent for Parkinson disease alone, but did not reach significance.
Both unilateral and bilateral oophorectomy performed prior to menopause may be associated with an increased risk of parkinsonism and the effect may be age-dependent. However, our findings await independent replication.
To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly ...diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as kappa/lambda (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint kappa/lambda FLC ratio of <0.03 or >32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of <0.03 or >32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin <3.5 g/dl and serum beta(2)-microglobulin >or=3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.
Chronic hyperglycemia relates to the occurrence of diabetic polyneuropathy (DPN), but has not yet been shown to relate to its overall severity In addition, the degree and duration of hyperglycemia, ...which measure of chronic hyperglycemia is most predictive of defined levels of severity of DPN, and which other putative risk factors are involved remain unknown.
In a longitudinal study of 264 diabetic individuals in Rochester, MN, risk factors and other diabetic complications assessed at regular intervals during an average of approximately 7 years were tested for their association with a composite score of severity of DPN at the last examination.
In multivariate analysis, diabetic retinopathy severity level (at last examination), mean ln(24-h proteinuria x duration of diabetes), and mean GHb were the main covariates for severity of DPN (R2 = 0.33). Excluding markers of microvessel and macrovessel disease, the independent risk factors were mean In(GHb x duration of diabetes), GHb, and type of diabetes (R2 = 0.23).
We found that diabetic microvessel disease, chronic hyperglycemia exposure, and type of diabetes are associated with severity of DPN, and we believe these factors are implicated in its cause. Each of the five markers of microvessel disease was a strong covariate for severity of DPN. Mean GHb predicts severity of DPN better than duration of diabetes, and the latter predicts severity of DPN better than mean fasting plasma glucose. Knowing the severity of microvessel disease, the degree of chronic hyperglycemia exposure, and the type of diabetes provides useful information to evaluate whether a coexisting polyneuropathy and its severity is probably due to diabetes.
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