Biomedical subjects

Sara J Achenbach

Publications and source records attributed to Sara J Achenbach.

At least 19 recordsLinked to original sources

PubMed2006

Long-term fracture risk among women with proven endometriosis.

OBJECTIVE: To determine whether women with pelvic endometriosis are at increased fracture risk. DESIGN: Historical cohort study. SETTING: Population-based investigation using the data resources of the Rochester Epidemiology Project. PATIENT(S): From Olmsted County, Minnesota, 987 women with endometriosis that was first surgically visualized or histologically proven in 1970-1989. INTERVENTION(S): None, observational study. MAIN OUTCOME MEASURE(S): Follow-up for fractures through complete inpatient and outpatient community medical records. RESULT(S): In 17,408 person-years of follow-up, 256 women experienced 449 different fractures. The cumulative incidence after 20 years (30.8%) was not elevated relative to that expected (30.6%). The independent predictors of any fracture included age (hazard ratio [HR] per 10 years: 1.61; 95% confidence interval [CI] 1.42-1.84]), corticosteroid use (HR: 2.78; 95% CI 1.48-5.24), prior hip, spine, or forearm fracture (HR: 1.82; 95% CI 1.10-3.02), and use of the selective estrogen receptor modulators, tamoxifen or raloxifene (HR: 4.34; 95% CI 2.14-8.81); physical activity was protective (HR: 0.40; 95% CI 0.18-0.88). There was no significant influence on fracture risk of surgery or other medical treatments for endometriosis. CONCLUSION(S): Despite reported adverse effects of treatment on bone density, there was no overall increase in long-term fracture risk in this unselected cohort of women with proven endometriosis.

Adolescent↗

PubMed2006

Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy.

CONTEXT: Despite a strong rationale for trials of somatostatin analogs in the treatment of Graves' ophthalmopathy (GO), recent studies have provided conflicting results. OBJECTIVE: The objective of the study was to determine whether octreotide long-acting release (LAR) is effective treatment for active GO. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. SETTING: The setting was a single tertiary referral center. PATIENTS: Twenty-nine consecutive euthyroid patients with active GO [clinical activity score (CAS) >or= 3] were enrolled; 25 completed the study. INTERVENTION: Patients received four monthly doses of either octreotide LAR (20 mg) or saline by im injections. MAIN OUTCOME MEASURES: Primary measure was a change in CAS; the secondary measure was changes in retrobulbar tissue volume, proptosis, lid fissure width, range of motion, and diplopia fields. RESULTS: Median (range) CAS change was 2.5 (1, 5) in the treatment and 1.0 (0, 7) in the placebo group (P = 0.02). Median lid fissure width improved in the treatment group, (decreased 1 mm on the right and 0.5 mm on the left), compared with the placebo group (no change on the right, P < 0.01; increased 1 mm on the left, P < 0.01). No other significant differences between groups were identified. CONCLUSIONS: CAS improved to a greater extent in octreotide-LAR-treated patients than the control group. However, this finding may not represent clinical benefit because patients with higher baseline CAS were overrepresented in the treatment group, and the control group was small. In contrast, treatment-related improvement in eyelid fissure width was noted, suggesting that octreotide LAR may be useful in the treatment of a subgroup of active GO patients with significant lid retraction.

Aged↗

PubMed2006

Bone turnover across the menopause transition: correlations with inhibins and follicle-stimulating hormone.

CONTEXT: Longitudinal clinical studies demonstrate that increases in bone turnover that occur in perimenopausal women correlate better with elevated serum FSH than with changes in serum estradiol (E2). This perimenopausal rise in FSH is due to a selective decrease in ovarian inhibin B (InhB). Our previous demonstration that inhibins suppress both osteoblast and osteoclast development suggests that changes in serum inhibins may regulate osteoblast and osteoclast differentiation and thereby bone turnover, independent of changes in sex steroids. OBJECTIVE: The objective of this study was to determine whether decreased serum inhibin A (InhA) and InhB levels correlate with increases in markers of bone turnover in women across the menopause transition and to evaluate serum inhibins as better predictors of bone turnover markers across the menopause transition than FSH or bioavailable E2. DESIGN: We studied a cross-sectional age-stratified population sample of 188 pre- and postmenopausal women not using oral contraceptives or hormone replacement therapy (age, 21-85 yr). RESULTS: Serum InhA and InhB levels significantly correlated inversely with markers of bone formation and bone resorption in pre- and perimenopausal women and with markers of bone formation in postmenopausal women (InhA only). FSH was not significantly correlated with bone turnover in either pre- or postmenopausal women; however, FSH was significantly correlated with bone resorption (C-terminal collagen I cross-link) in perimenopausal women (age, 45-54 yr). Using multivariate analyses, serum InhA better predicted bone formation and resorption markers in premenopausal women than either FSH or bioavailable E2. CONCLUSIONS: Decreases in inhibin levels across the menopause transition are associated with increasing bone turnover, regardless of changes in sex steroids or FSH.

Adult↗

PubMed2006

Fracture risk after the diagnosis of Parkinson's disease: Influence of concomitant dementia.

In an inception cohort of 196 Olmsted County, Minnesota, residents with Parkinson's disease (PD) first recognized in 1976 to 1995, we tested whether the increased risk of bone fractures is associated with concomitant dementia. Using the data resources of the Rochester Epidemiology Project, information about PD, dementia, other clinical risk factors for fracture and fracture events was obtained from review of complete inpatient and outpatient medical records spanning each subject's residence in the community. Compared to an equal number of age- and sex-matched non-PD referent subjects from the community, PD patients were at a 2.2-fold increased risk of fractures generally and a 3.2-fold greater risk of hip fractures specifically. Adjusting for age, the independent predictors of overall fracture risk in the PD subjects included female sex (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.1-2.3), dementia (HR, 1.6; 95% CI, 1.1-2.4) and chronic depression, which was associated with a reduced risk (HR, 0.4; 95% CI, 0.2-0.8). Hip fractures were predicted by dementia (HR, 2.2; 95% CI, 1.2-4.1). The increased fracture risk in patients with PD is not entirely explained by concomitant dementia, and additional study is needed to determine the relative contributions to fracture risk of falls versus bone loss in these patients.

Adult↗

PubMed2006

Hearing loss in rheumatoid arthritis.

OBJECTIVE: The objective of this study was to evaluate whether patients with rheumatoid arthritis (RA) are more likely to have subclinical hearing loss compared with persons without RA. METHODS: This is a case-control cross-sectional study of 29 patients with RA with disease duration greater than 5 years. Five males and five females were recruited into each decade category (age 40-49, 50-59, and 60-69). These cases were matched in a 1:1 ratio by sex and age to 30 control subjects. A comprehensive set of audiometric and disease severity assessments were performed. RESULTS: Seventeen (59%) of 29 patients with RA had abnormal hearing for at least one frequency (four in one ear, 13 in two ears) by audiometry as did 14 (47%) of 30 control subjects (five in one ear, nine in two ears). The percentage of patients with hearing loss (% RA vs. % control subjects) was: 45% versus 40% sensorineural, 10% versus 7% conductive, and 3% versus 0% mixed hearing loss. In RA versus control subjects, acoustic reflex threshold was abnormal in 17% versus 7%; speech reception threshold was abnormal in 10% versus 3%. Tympanometry and otoacoustic emission findings were similar in both groups. Word recognition did not differ between patients with RA and control subjects. In patients with RA/control subjects, hearing handicap, dizziness, and health assessment questionnaires were abnormal in 28%/7%, 14%/3%, and 72%/7%, respectively. CONCLUSION: There was no difference found in objective audiometric measurements in patients with RA compared with non-RA control subjects. Subjectively patients with RA were more likely to perceive themselves as having hearing disturbances, which may be related to overall disease related functional impairment.

Acoustic Impedance Tests↗

PubMed2006

Does reduced skeletal loading account for age-related bone loss?

UNLABELLED: A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21-97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging. INTRODUCTION: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail. MATERIALS AND METHODS: In a stratified random sample of Rochester, MN, women and men 21-97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (H(o)) that bone strength per unit load did not vary with age. RESULTS AND CONCLUSIONS: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p = 0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.

Adult↗

PubMed2005

Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men.

CONTEXT: Using high-resolution three-dimensional peripheral quantitative computed tomography (3D-pQCT) imaging, we recently described sex and age effects on bone microstructure at the ultradistal radius in men and women. Although bone volume/tissue volume decreased with age in both sexes, changes in trabecular number (TbN) and thickness (TbTh) in men were complex, with evidence for conversion of thick trabeculae into more numerous, thinner trabeculae in young men. OBJECTIVE: Our objective was to define the relationship between hormonal and bone turnover variables and trabecular microstructure at the ultradistal radius. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based, cross-sectional study in the general community that included 205 women and 269 men, aged 21-97 yr. MAIN OUTCOME MEASURES: We measured correlation of bone volume/tissue volume, TbN, TbTh, and trabecular separation with hormonal and bone turnover variables. RESULTS: In young men (20-39 yr), TbTh and TbN were associated with serum IGF-I levels (r = 0.31, P < 0.05 and r = -0.35, P < 0.01, respectively). No associations were found between sex steroid levels (bioavailable estradiol or testosterone) or biochemical markers of bone turnover and trabecular parameters in young men or women. By contrast, in elderly men and women (>60 yr), sex steroids were the most consistently associated with trabecular microstructure, and bone turnover markers were variably associated with these parameters. CONCLUSIONS: In young men, the apparent conversion of thick trabeculae into more numerous, thinner trabeculae is most closely associated with declining IGF-I levels. By contrast, sex steroids are the major hormonal determinants of trabecular microstructure in elderly men and women.

Adult↗

PubMed2005

CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis.

Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS.

Adult↗

PubMed2005

Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease.

UNLABELLED: We updated the incidence of primary hyperparathyroidism in Rochester, Minnesota. The lower rates previously noted persisted, whereas parathyroidectomies at our institution remained high. These data suggest an etiologic factor may be responsible for the peak incidence in the 1970s. INTRODUCTION: Automated serum calcium measurements were associated with a dramatic rise in primary hyperparathyroidism in the early 1970s, but a progressive decline in the incidence thereafter was unexpected and suggested a fundamental change in the epidemiology of the disease. Our objective was to evaluate trends in the incidence of primary hyperparathyroidism since 1992. MATERIALS AND METHODS: In this population-based descriptive study, Rochester, MN, residents who met defined diagnostic criteria for primary hyperparathyroidism from January 1993 through December 2001 were identified through the medical record linkage system of the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System. Changes in incidence were evaluated by Poisson regression. RESULTS: Altogether, 136 Rochester residents (94 women and 42 men) were newly identified with primary hyperparathyroidism in 1993-2001. Their mean age was 56 years, and 93% had definite disease. The overall age- and sex-adjusted (to 2000 U.S. whites) rate during this period was 21.6 per 100,000 person-years, which was less than the annual rate of 29.1 per 100,000 observed in 1983-1992 and 82.5 per 100,000 in July 1974-1982. Although community incidence declined, the number of parathyroidectomies performed at our institution increased during the same period. Serum calcium was deleted from the automated chemistry panel in June 1996, but most subjects remained asymptomatic at diagnosis (95%) with mild hypercalcemia. The majority of subjects were observed without parathyroid surgery (75%), and there was minimal impact on patient management from the 1990 NIH consensus conference on asymptomatic primary hyperparathyroidism. CONCLUSIONS: The lower incidence of primary hyperparathyroidism noted through 1992 has persisted in our community through 2001, whereas parathyroidectomies at our institution remained high. These data suggest that some underlying etiologic factor, in addition to the introduction of automated serum calcium testing, may have been responsible for the peak incidence in the 1970s.

Calcium↗

PubMed2005

Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women.

CONTEXT: Although estrogen clearly plays a central role in regulating bone mass in women, studies in men have suggested that there may be a threshold bioavailable (bio) estradiol (E2) level below which aging men begin to lose bone and that the threshold for estrogen deficiency in cortical bone may be considerably lower than that in trabecular bone. There are no data testing this in women. OBJECTIVE: Our objective was to assess volumetric bone mineral density (vBMD) and bone geometry by quantitative computed tomography and relate these to circulating bio E2 and bio testosterone levels. DESIGN: We studied a cross-sectional, age-stratified population sample of 235 women (age, 21-97 yr). RESULTS: vBMD/structural parameters were not related to sex steroid levels in young premenopausal women (age, 20-39 yr) with a median bio E2 level of 17 pg/ml (63 pmol/liter). By contrast, bio E2 and bio testosterone levels were both significantly associated with trabecular and cortical vBMD and cortical area at multiple sites in late postmenopausal women (age > or = 60 yr) who had a median bio E2 level of 3 pg/ml (11 pmol/liter). Late premenopausal and early postmenopausal women (age, 40-59 yr) with an intermediate median bio E2 level of 11 pg/ml (42 pmol/liter) showed age-adjusted correlations of bio E2 levels with trabecular but not with cortical vBMD. CONCLUSIONS: In women, bio E2 levels are associated with vBMD and some structural bone parameters at low but not high bio E2 levels. Similar to findings in men, the threshold for estrogen deficiency in cortical bone in women appears to be lower than that in trabecular bone.

Adult↗

PubMed2005

Osteoporosis assessment by whole body region vs. site-specific DXA.

The ability of regional data from whole body scans to provide an accurate assessment of site-specific BMD, osteoporosis prevalence and fracture risk has not been fully explored. To address these issues, we measured total body (TBBD) and site-specific BMD in an age-stratified population sample of 351 women (21-93 years) and 348 men (22-90 years). We found an excellent correlation between AP lumbar spine and total body lumbar spine subregion BMD (r2=0.92), but weaker ones for total hip compared to pelvis region (r2=0.72) or between total wrist and left arm subregion from the whole body scan (r2=0.83). The error in estimating site-specific BMD from total body regions ranged from 4.3% (lumbar spine) to 11.2% (femoral neck) in women and from 4.9 to 11.1%, respectively, in men. Site-specific versus regional measurements at the lumbar spine and total hip/pelvis provided comparable overall estimates of osteoporosis prevalence, but disagreed on the status of individuals; measurements at whole body regions underestimated osteoporosis as assessed at the femoral neck or total wrist. All measurements were associated with a history of various fractures [age adjusted odds ratios (OR), 1.3 to 2.1 in women and 1.2 to 1.5 in men] and were generally interchangeable, but femoral neck BMD provided the best estimate of osteoporotic fracture risk in women (OR, 2.9; 95% CI, 1.7-5.0). Although there are strong correlations between BMD from dedicated scans of the hip, spine and distal forearm and corresponding regions on the whole body scan, the measurements provide somewhat different estimates of osteoporosis prevalence and fracture risk.

Absorptiometry, Photon↗

PubMed2005

Contributions of bone density and structure to fracture risk assessment in men and women.

Although bone mineral density (BMD) is a strong predictor of fractures, it is only a surrogate for bone strength. Bone structural parameters can now be measured on BMD scans, but it is unclear whether they would be more useful for risk assessment. We measured structural parameters using the Hip Structural Analysis Program and evaluated their association, compared with standard hip BMD, with fracture risk in a population-based sample of 213 postmenopausal women and 200 men > or =50 years of age. Altogether, 38% of the women and 27% of the men had experienced a fracture due to moderate trauma (half involved hip, spine or distal forearm), while 23% and 36%, respectively, had a previous fracture due to severe trauma. In logistic regression analyses adjusted for age, the hip BMD and structural parameters were all associated with moderate trauma fractures generally, and osteoporotic fractures specifically, in women, but the best predictor in a multivariate model was femoral neck BMD (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.9-4.0). BMD and the structural parameters were strongly correlated, however, and could be interchanged with little reduction in predictive power. These variables were less predictive of moderate trauma fractures in men. The best model included age (OR per 10 years, 1.5; 95% CI, 1.1-2.1), femoral neck section modulus (OR, 1.6; 95% CI, 1.1-2.5) and intertrochanteric buckling ratio (OR, 1.6; 95% CI, 1.3-2.0). Correction for body size did not alter these relationships. Fractures due to severe trauma were best predicted by structural parameters: in women, femoral neck buckling ratio (OR, 1.2; 95% CI, 1.04-1.5) and, in men, intertrochanteric buckling ratio (OR, 1.4; 95% CI, 1.2-1.6). These data suggest that selected structural variables as assessed by dual-energy X-ray absorptiometry would be as good as standard BMD measurements for predicting fracture risk. Because of the strong correlations, however, some judgment can be used in selecting the variables easiest to measure.

Absorptiometry, Photon↗

PubMed2005

Long-term trends in thyroid carcinoma: a population-based study in Olmsted County, Minnesota, 1935-1999.

OBJECTIVE: To determine whether there was a significant increase in the incidence of thyroid carcinoma in Olmsted County, Minnesota, that may be attributed to the widespread use of therapeutic head and neck irradiation between 1920 and the 1950s or to exposure to atomic fallout at the Nevada Test Site in the 1960s. METHODS: Rochester Epidemiology Project resources were used to identify potential cases of thyroid carcinoma among residents of Olmsted County between 1935 and 1984. We extended this earlier study through 1999. RESULTS: During the study period, thyroid carcinoma was newly diagnosed in 263 residents. In women, the age-adjusted incidence increased from 2.7 per 100,000 person-years (p-y) in 1935-1949 to 9.2 per 100,000 p-y in 1990-1999 (P = .001); In men, the rate increased from 0.8 to 5.0 per 100,000 p-y (P = .007). However, most of the increase occurred before 1965 and remained relatively stable thereafter. Similar trends were observed for papillary carcinoma alone. CONCLUSION: Although the Incidence of thyroid carcinoma increased significantly between 1935 and 1964, no significant Increases have been seen since 1965, suggesting that neither atmospheric atomic fallout from the Nevada Test Site nor use of ionizing radiation to treat conditions of the head and neck significantly affected the incidence of thyroid carcinoma in Olmsted County.

Adolescent↗

PubMed2004

Long-term fracture risk among children with asthma: a population-based study.

UNLABELLED: Fracture risk among patients diagnosed with asthma in childhood is greater in males and oral corticosteroid users, but most fractures are of the appendicular skeleton and may relate to impaired skeletal development. INTRODUCTION: There are no population-based data on fracture outcomes among the growing number of patients with asthma diagnosed in childhood. MATERIALS AND METHODS: We conducted a population-based retrospective (historical) cohort study among 279 Rochester, Minnesota, residents who were <35 years of age (mean, 6.2 years) when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and cases were compared directly with age- and sex-matched controls in a stratified proportional hazards model. Risk factors for fractures among the asthma cases were assessed using Andersen-Gill time-to-fracture regression models. RESULTS: During 6649 person-years of follow-up (median, 24.3 years/subject), 107 asthma patients experienced 189 fractures, for a crude fracture incidence rate of 2.8 per 100 person-years. The actuarially estimated cumulative fracture incidence after 20 years was 40% compared with 34% among controls (p = 0.122). There was no significant increase in overall fracture risk among cases compared to their age- and sex-matched controls (hazard ratio [HR], 1.3; 95% CI, 0.9-1.9), but males with asthma had a 2.6-fold greater risk of hand and finger fractures than control males. The independent predictors of overall fracture risk among the asthma patients included male gender (HR, 2.2; 95% CI, 1.5-3.2) and use of oral corticosteroids (HR, 2.0; 95% CI, 1.2-3.1) or anti-cholinergic agents (HR, 3.9; 95% CI, 1.5-10). CONCLUSIONS: Rather than osteoporotic fractures of the axial skeleton, oral corticosteroid therapy was associated here with limb fractures, suggesting a relationship with impaired development of a biomechanically competent skeleton. Additional studies are needed to assess this possibility.

Adolescent↗

PubMed2004

Fracture risk with multiple myeloma: a population-based study.

UNLABELLED: Pathologic fractures, especially of the axial skeleton, are extremely common in patients with multiple myeloma and cluster around the time of diagnosis. Osteoporotic fractures seem to be less of a problem in these patients. INTRODUCTION: It is generally believed that fractures are common in patients with multiple myeloma as a result of lytic bone lesions, generalized bone loss, and/or elevated bone turnover from excessive cytokine production, but the actual risk of pathologic versus osteoporotic fractures has not been quantified. MATERIALS AND METHODS: In a population-based retrospective cohort study, 165 Olmsted County, MN, residents with myeloma diagnosed from 1945 to 2001 (55% men; mean age, 70.7 +/- 11.1 years) were followed for 537 person-years. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS: Altogether, 134 patients experienced 463 fractures. In the year before diagnosis, 16 times more fractures were observed than expected, mostly pathologic fractures of the vertebrae and ribs. Subsequently, there was a 9-fold increase in fracture risk. However, 69% of these fractures were pathologic, and another 11% were found incidentally on myeloma monitoring. With the latter two groups excluded, subsequent fracture risk was elevated 3-fold, with a 2-fold increase in the risk of an osteoporotic fracture. In multivariate analyses, the predictors of overall fracture risk were oral corticosteroid use and elevated serum calcium levels, whereas pathologic fractures were additionally predicted by use of chemotherapy. CONCLUSION: There is a dramatic increase in fractures around the time of diagnosis of myeloma, most of which are pathologic fractures. The most important predictor of overall fracture risk is oral corticosteroid use.

Adrenal Cortex Hormones↗

PubMed2004

Long-term fracture risk following adult-onset asthma: a population-based study.

There are few data on skeletal outcomes in the growing population of patients with adult-onset asthma. We conducted a population-based retrospective (historical) cohort study among 226 residents of Rochester, Minnesota, USA, who were 35 years of age or older when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and observed fractures were compared with expected numbers based on incidence rates in the local population (standardized incidence ratios, SIR). During 4,022 person-years of follow-up, 100 patients experienced 211 fractures, for an actuarially estimated cumulative incidence of 63% after 30 years compared with 59% expected ( p=0.004). Statistically significant increases were seen for moderate trauma fractures of the vertebrae (SIR, 2.9; 95% CI, 2.1 to 3.8) and ribs (SIR, 2.0; 95% CI, 1.2 to 3.2), as well as the proximal femur (SIR, 1.8; 95% CI, 1.02 to 2.8). As assessed by proportional hazards models, the only independent predictors of any subsequent moderate trauma fracture were age (hazard ratio [HR] per 10-year increase, 1.7; 95% CI, 1.5 to 2.1) and cumulative corticosteroid dose greater than the median of 1,775 mg (HR, 1.8; 95% CI, 1.1 to 3.0). In another multivariate analysis, the predictors of a moderate trauma vertebral fracture were older age (HR, 1.6; 95% CI, 1.3 to 2.1), concomitant chronic obstructive pulmonary disease (HR, 2.4; 95% CI, 1.2 to 4.9), cigarette smoking (HR, 2.3; 95% CI, 1.2 to 4.8), and cumulative corticosteroid dose greater than the median (HR, 2.6; 95% CI, 1.4 to 5.0). Other asthma therapies did not contribute significantly to these models. Thus, a 70% increase in overall fracture risk among unselected community patients with adult onset asthma was mainly confined to the subset who also had chronic obstructive pulmonary disease and was influenced by substantial corticosteroid use.

Accidental Falls↗

PubMed2004

CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS.

CD95/CD95L interaction results in activation-induced apoptosis thereby regulating clonal expansion of T cells outside the thymus. Genetic defects in this system result in autoimmune lymphoproliferation in mice and men. CD95-induced cell death may be defective in MS. We studied the association of CD95 and CD95L polymorphisms with MS in 221 unique patients representing 79% ascertainment in Olmsted County, MN, and 442 gender-, age- and ethnicity-matched controls. Being a homozygote for the G allele of CD95 5'(-670)*A-->G SNP (p=0.034; OR: 1.59, 95% CI: 1.06-2.38) and for the C allele of CD95 E7(74)*C-->T SNP (p=0.007; OR: 1.73, 95% CI: 1.17-2.56) increased susceptibility to MS exclusively in women. There was strong but incomplete linkage disequilibrium between the two markers (p<0.001; D'=0.546). Homozygosity for 5'(-670)*A or E7(74)*C explained 28% of risk of MS in women but 0% of the risk in men in Olmsted County, MN. Our results agree with the previously published studies and highlight that the association of the polymorphisms is restricted to women with MS. We did not find an association between CD95L and susceptibility to MS nor CD95 or CD95L and age of onset, disease course and disease severity.

Cohort Studies↗

PubMed2004

Fracture risk in monoclonal gammopathy of undetermined significance.

UNLABELLED: To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.

Accidental Falls↗