W. M. O'Fallon

Treatment of postmenopausal osteoporosis with transdermal estrogen.

OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING Referral-based outpatient clinic. PATIENTS Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.

Prevalence and incidence of vertebral deformities.

There is a need to identify vertebral fractures from radiographs taken at a single point in time, but considerable controversy surrounds the methods to be used. We extended a data set to comprise baseline radiographs of the thoracic and lumbar spine on an age-stratified random sample of 762 Rochester, Minnesota, women and used revised methods to define vertebral deformities morphometrically. Changes in the method of measuring vertebral heights, changes in the source of normal values for vertebral measurements and changes in the criteria for assessing vertebral deformity had little impact on estimated prevalence and incidence in this population. The prevalence of any vertebral deformity was estimated at 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3–28.2), while the incidence of a new deformity in this group was estimated at 17.8 per 1000 person-years (95% CI, 16.0–19.7). Projected nationally, these data suggest that over 500 000 white women in the United States develop vertebral deformities for the first time each year and that over 7 million white women aged 50 years and over might be affected at any given time. These estimates are limited by the absence of a reliable ‘gold standard’ with which to determine false positive and false negative rates associated with this or any other morphometric method. Information on the health consequences of vertebral deformities of various sorts would be most helpful in choosing between alternative approaches to defining them.

Relapsing polychondritis. Survival and predictive role of early disease manifestations.

To define the natural history of relapsing polychondritis, the probability of survival and causes of death were determined in 112 patients seen at one institution. By using covariate analysis, early clinical manifestations were identified that predicted mortality. The 5- and 10-year probabilities of survival after diagnosis were 74% and 55%, respectively. The most frequent causes of death were infection, systemic vasculitis, and malignancy. Only 10% of the deaths could be attributed to airway involvement by chondritis. Anemia at diagnosis was a marker for decreased survival in the entire group. There was an interaction between other disease variables and age in determining their impact on outcome. For patients less than 51 years old, saddle-nose deformity and systemic vasculitis were the worst prognostic signs. For older patients, only anemia predicted outcome. The need for corticosteroid therapy did not influence survival.

Vertebral fractures predict subsequent fractures.

Abstract: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.

Dementia after ischemic stroke A population-based study in Rochester, Minnesota (1960-1984)

Article abstract-We used the medical records linkage system for the population of Rochester, Minnesota, to identify persons in the community who had their first cerebral infarct without previous dementia. In this cohort (n = 971), the incidence of dementia in the first year was nine times greater than expected, but if we did not observe dementia in the first year, the risk of dementia in the cohort each year thereafter was about twice the risk in the population. After the first year, a 50% increase was observed in Alzheimers disease in the cohort compared with that in the community. Although the incidence of dementia increased with increasing age, the standardized morbidity ratios decreased with increasing age. Age, sex (male), and second stroke were significant independent predictors of dementia in a multivariate Cox proportional hazards model. There was no effect of location or clinical severity of infarct on the rate of occurrence of dementia. NEUROLOGY 19;: 154-159

Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980

The incidence of carpal tunnel syndrome in the population of Rochester, Minnesota, from 1961 through 1980 was determined by use of the medical records-linkage system of the Rochester Epidemiology Program Project at the Mayo Clinic; 1, 016 patients (1, 600 affected hands) were identified. Incidence (cases per 100, 000 person-years) was 99 (crude) overall, whereas the age-adjusted rates were 52 for the men, 149 for the women, and 105 for both sexes combined. Age-adjusted incidence rates increased from 88 during the 1961 to 1965 quinquennium to 125 during the 1976 to 1980 quinquennium; these rates probably reflect better recognition rather than a true increase in incidence rates. Age-specific rates generally increased with age in men, whereas in women a peak was reached in the 45 to 54 age group.

Value of Immunological Markers in Predicting Responsiveness to Influenza Vaccination in Elderly Individuals

ABSTRACT Elderly individuals are at high risk for morbidity and mortality when infected with influenza virus. Vaccinations with inactivated virus are less effective in the elderly due to the declining competency of the aging immune system. We have explored whether immunological parameters predict poor anti-influenza virus vaccine responses and can be used as biological markers of immunosenescence. One hundred fifty-three residents of community-based retirement facilities aged 65 to 98 years received a trivalent influenza vaccine. Vaccine-induced antibody responses were determined by comparing hemagglutination inhibition titers before and 28 days after immunization. The composition of the T-cell compartment was analyzed by flow cytometry and the sizes of three T-cell subsets, CD4+CD45RO+ cells, CD4+ CD28null cells, and CD8+ CD28null cells, were determined. Only 17% of the vaccine recipients were able to generate an increase in titers of antibody to all three vaccine components, and 46% of the immunized individuals failed to respond to any of the three hemagglutinins. The likelihood of successful vaccination declined with age and was independently correlated with the expansion of a particular T-cell subset, CD8+ CD28null T cells. The sizes of the CD4+ CD45RO+ memory T-cell and CD4+ CD28null T-cell subsets had no effect on the ability to mount anti-influenza virus antibody responses. Frequencies of CD8+ CD28null T cells are useful biological markers of compromised immunocompetence, identifying individuals at risk for insufficient antibody responses.

Survival and recurrence after first cerebral infarction : A population-based study in Rochester, Minnesota, 1975 through 1989

We used the Kaplan-Meier product limit method to estimate rates and Cox proportional hazards regression analysis with bootstrap validation to model significant independent predictors of and temporal trends in survival and recurrent stroke among 1,111 residents of Rochester, MN, who had a first cerebral infarction from 1975 through 1989. The risk of death after first cerebral infarction was 7% ± 0.7% at 7 days, 14% ± 1.0% at 30 days, 27% ± 1.3% at 1 year, and 53% ± 1.5% at 5 years. Independent risk factors for death after first cerebral infarction were age(p < 0.0001), congestive heart failure (p < 0.0001), persistent atrial fibrillation (p < 0.0001), recurrent stroke (p < 0.0001), and ischemic heart disease (p< 0.0001 for age ≤70, p > 0.05 for age >70). The risk of recurrent stroke after first cerebral infarction was 2% ± 0.4% at 7 days, 4% ± 0.6% at 30 days, 12% ± 1.1% at 1 year, and 29%± 1.7% at 5 years. Age (p = 0.0002) and diabetes mellitus(p = 0.0004) were the only significant independent predictors of recurrent stroke. Neither the year nor the quinquennium of the first cerebral infarction was a significant determinant of survival or recurrence. The temporal trend toward improving survival after first cerebral infarction documented in Rochester, MN, in the decades before 1975 has ended.

Fracture Incidence in Olmsted County, Minnesota: Comparison of Urban with Rural Rates and Changes in Urban Rates Over time

Abstract: Using the data resources of the Rochester Epidemiology Project, we carried out a descriptive study of fracture incidence among the residents of Olmsted County, Minnesota. During the 3-year period 1989–91, 2901 County residents ≥ 35 years of age experienced 3665 separate fractures. The age- and sex-adjusted (to 1990 United States whites) incidence of any fracture was 2205 per 100 000 person-years (95% CI, 2123 to 2286) and that of all fractures was 2797 per 100 000 (95% CI, 2705 to 2889). Age-adjusted fracture rates were 40% greater among women. Incidence rates increased with age in both sexes. One-third of the fractures involved the hip, spine or distal forearm – the skeletal sites traditionally associated with osteoporosis. The age- and sex-adjusted incidence of fractures due to moderate trauma (2205 per 100 000 person-years; 95% CI, 2106 to 2303) was twice that of fractures due to more severe trauma (1164 per 100 000; 95% CI, 1106 to 1223) and 12 times that of pathological fractures (178 per 100 000; 95% CI, 133 to 222). Overall fracture rates were 15% greater among residents of the central city of Rochester compared with the rural portion of Olmsted County. The incidence of limb fractures among Rochester residents was 14% higher than comparable rates documented for this community 20 years earlier in 1969–71, due mainly to a substantial increase in the incidence of leg fractures.

Incidence rates of stroke in the eighties: the end of the decline in stroke?

Studies of the population of Rochester, Minnesota, have provided the only data on temporal trends for the incidence of stroke in North America. Among the residents of Rochester, the average annual incidence rate of stroke declined by 46%, from 213 to 115 per 100,000 population, between 1950-1954 and 1975-1979. The decline occurred in all age and sex groups, but it occurred earlier in women than in men. The rates stabilized in the 1970s, and did so earlier in women. For 1980-1984, the incidence rate of stroke was 17% higher than that for 1975-1979. The onset of the decline in incidence rates coincided with the introduction of effective antihypertensive therapy, but stabilized and increased rates were associated with continuing improvement in the control of hypertension. The increase in the incidence rates of stroke coincided with the introduction of computed tomography, which appeared to increase the detection of less severe strokes.