Citations

AbstractIn a population-based retrospective cohort study, Rochester women aged 35–69 years who were first diagnosed with one or more vertebral fractures in 1950–1979 were followed for the development of a subsequent hip fracture. The 336 women with no history of hip fracture at the time of their vertebral fracture experienced 52 proximal femur fractures in 4788 person-years of follow-up. The standardized morbidity ratio (SMR) of observed to expected hip fractures was 1.8 (95% CI, 1.3–2.4) and was higher for intertrochanteric than cervical femoral fractures (SMR, 2.3 versus 1.3; P = 0.07). Hip fracture risk among women with symptomatic vertebral fractures was slightly less than in those with asymptomatic vertebral fractures (SMR, 1.8 versus 2.3; not significant), and younger women had no higher risk of a subsequent hip fracture than women who were ≥60 years of age at the time of their vertebral fracture (SMR, 1.4 versus 1.8; not significant). Alternative explanations are possible, but these data are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures.

Abstract To assess the influence on the risk of hip fractures in men of medical conditions associated with secondary osteoporosis or with an increased likelihood of falling, we conducted a population-based nested case-control study among the 232 Rochester, Minnesota, men with an initial hip fracture due to moderate trauma in 1965–1989 and an equal number of age-matched control men from the general population. Information on selected medical and surgical conditions and certain behavioral risk factors prior to fracture (or comparable index date for controls) was obtained from inpatient and outpatient medical records in the community that averaged over 36 years in duration. After adjusting for age, obesity, and inactivity, disorders linked with secondary osteoporosis were associated with a 2-fold increase in the risk of hip fracture in men (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.3–4.3), while conditions linked with an increased risk of falling were associated with almost a 7-fold increase in risk (OR 6.9; 95% CI 3.3–14.8). These factors together appeared to account for about 72% of the hip fractures in men. Increased attention must be paid to these conditions which, in aggregate, are very common in elderly men and lead to a substantial increase in the risk of hip fracture with its devastating sequelae of death, disability, and cost.

Abstract Increasing body weight is associated both with higher bone mass and with lower rates of bone loss. Whether the effects of body weight are mediated by lean body mass (LBM) or fat body mass (FBM) is, however, uncertain because different studies have used different measures of bone mass and arrived at contradictory conclusions. The parameter actually measured is bone mineral content (BMC). Bone mineral density (BMD), bone mineral apparent density (BMAD), and the BMD/height attempt to “correct” BMC for differences in bone or body size, but these corrections may bias the analysis of the effects of body composition on the skeleton. To resolve this issue, we measured BMC at the total body, lumbar spine, proximal femur, and forearm using dual energy X-ray absorptiometry (DXA) in a population-based sample including 138 premenopausal women (age range 21–54 years, mean 35 years) and 213 postmenopausal women (age range 34–94 years, mean 68 years). BMD, BMAD, and BMD/ height were also calculated for each site. LBM and FBM were determined from the DXA whole body scan. In a multivariate analysis that included age and height, both LBM and FBM predicted total body BMC in pre- and postmenopausal women (p < 0.002 for LBM and FBM in both groups). LBM had a dominant effect on spine and forearm BMC in both groups (p < 0.004) and hip BMC in premenopausal women (p < 0.001), whereas both LBM and FBM predicted hip BMC in postmenopausal women (p < 0.001). However, as BMC was adjusted for bone or body size using BMD, BMAD, or BMD/height, FBM tended to become more important than LBM in the analysis. This was, in part, due to the fact that each of the correction factors in the BMD and BMAD calculations, as well as height, were highly correlated with LBM (r = 0.57 and 0.52 for height versus LBM in pre- and postmenopausal women, respectively [p < 0.001]), and weakly or not at all with FBM (r = 0.08 and 0.11, respectively). Therefore, dividing BMC by these correction factors tended to bias the analysis against potential effects of LBM on bone mass. Thus, the relationship between body composition and bone mass is critically dependent on which bone mass parameter is used in the analysis. Both LBM and FBM have important effects on bone mass, depending on the bone mass parameter used, the skeletal site measured, and menopausal status.

Abstract Vertebral fractures are the classic hallmark of osteoporosis, yet little is known of their epidemiology. The incidence of clinically diagnosed vertebral fractures was therefore directly assessed in the predominantly white (European descent) population of Rochester, Minnesota. Altogether, 341 Rochester residents were radiologically diagnosed for the first time with one or more vertebral fractures in the 5 year study period, 1985–1989. The overall age- and sex-adjusted incidence rate was 117 per 100,000 person-years (95% CI, 105 to 130). The age-adjusted rate in women (145 per 100,000 person-years) was almost twice that in men (73 per 100,000 person-years). Of all fractures, 47 (14%) followed severe trauma, 282 (83%) followed moderate or no trauma, and 12 (3%) were pathologic. Incidence rates for fractures following moderate trauma were higher in women than in men and rose steeply with age in both genders. In contrast, fractures following severe trauma were more frequent in men, and their incidence increased less with age. These Rochester rates are greater than those previously reported from studies in Britain and Sweden but lower than the incidence rates extrapolated from a prevalence study in this population.

Abstract Bone mineral density (BMD) was measured at the lumbar spine and cervical and intertrochanteric regions of the proximal femur by dual-photon absorptiometry and bone mineral content was assessed at the distal and midradius by single-photon absorptiometry in an age-stratified random sample of 304 Rochester, Minnesota women aged 30–94 years. Over follow-up extending to 10 years (median 8.3 years), 93 women experienced 163 new fractures. After adjusting for age, these bone mineral measurements predicted the likelihood of any incident fracture due to moderate trauma, with relative hazards varying from 1.4 to 1.6 per SD decrease in baseline bone mineral. A 1 SD decrease in lumbar spine BMD increased the risk of a new vertebral fracture comparably to a 17 year increase in age; a 1 SD decrease in femoral BMD was comparable to a 13–14 year increase in age on the risk of a hip fracture. We conclude that bone mineral measurements made at a variety of skeletal sites can predict the occurrence for at least 8–10 years of moderate trauma fractures of the sort that might be related to osteoporosis.

The severity of asthma, a disease characterized by airway hyperresponsiveness and inflammation, is enhanced in some women during the menstrual cycle and during pregnancy but relieved in others. These clinical findings suggest that sex steroids modulate airway tone. Based on well-known relaxant effects of estrogens on vascular smooth muscle, we hypothesized that estrogens relax airway smooth muscle (ASM), thus facilitating bronchodilation. In ASM tissues from female patients, Western and immunocytochemical analyses confirmed the presence of both estrogen receptor (ER) isoforms, ERα and ERβ. In fura 2-loaded, dissociated ASM cells maintained in culture, acute exposure to physiological concentrations of 17β-estradiol (E2; 100 pM to 10 nM) decreased the intracellular Ca2+ ([Ca2+]i) response to 1 μM histamine, an effect reversed by the ER antagonist ICI-182,780. The ERα-selective agonist (R,R)-THC had a greater reducing effect on [Ca2+]i responses to histamine and 1 μM ACh compared with the ERβ-selective agonist (DPN). The effects of E2 on [Ca2+]i were mediated, at least in part, via decreased Ca2+ influx through l-type channels and store-operated Ca2+ entry but not via Ca2+-activated K+ channels, receptor-operated entry, or sarcoplasmic reticulum reuptake. Overall, these data support our hypothesis that estrogens relax ASM and suggest a potentially novel therapeutic target in airway hyperresponsiveness.

Until recently, neuromyelitis optica (NMO) was considered to be a sub-type of multiple sclerosis (MS), which has a strong predilection for Caucasian populations, whereas NMO is more frequent in non-Caucasian individuals. The objective of this study was to compare the HLA-DRB profile in Brazilian Mulatto patients with NMO spectrum disorders (NMOSDs) with that observed for Mulatto MS patients and healthy Mulatto controls. Twenty seven NMOSD patients (20 women), all seropositive for NMO-IgG, 29 MS patients and 28 Mulatto healthy blood donors were evaluated for HLA-DRB allele groups. HLA-DRB1*03 allele group was overrepresented in NMO patients compared with healthy controls (p = 0.0401; OR = 3.23, 95%CI: 1.07—9.82). In contrast, the HLA-DRB1*15 allele group was overrepresented in Brazilian MS patients (OR = 15.89, 95%CI: 3.51—71.85; p < 0.0001). DRB3 was overrepresented in NMO (p = 0.0064), and DRB5 overrepresented in MS patients (p = 0.0001). The low frequency of HLA-DRB1*15 alleles was associated with the presence of long and central cord lesions at magnetic resonance. In addition, DRB1*15 alleles were associated with the fulfillment of the Barkhof criteria. In conclusion, these results indicate that the DRB profile of NMO patients is different from that observed for MS patients, further corroborating the distinction between NMO and MS.