Biomedical subjects

Sara J Achenbach

Publications and source records attributed to Sara J Achenbach.

28 records · Page 2Linked to original sources

PubMed2003

Long-term fracture risk following renal transplantation: a population-based study.

Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965-1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject's complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected ( P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6-6.4] and vertebral (SIR, 23.1; 95% CI, 12.3-39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1-12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.

Adolescent↗

PubMed2003

Incidence of childhood distal forearm fractures over 30 years: a population-based study.

CONTEXT: The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth. Changes in physical activity or diet may therefore influence risk of forearm fracture. OBJECTIVE: To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years. DESIGN, SETTING, AND PATIENTS: Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001. MAIN OUTCOME MEASURE: Estimated incidence of distal forearm fractures in 4 time periods. RESULTS: Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001. Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P =.01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001). The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls. CONCLUSIONS: There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present. Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.

Adolescent↗

PubMed2003

Role of parathyroid hormone in mediating age-related changes in bone resorption in men.

Osteoporosis in men is an important and growing public health problem. While there has been extensive work done on defining the mechanism(s) of the age-related increase in bone resorption in women, our knowledge regarding the pathogenesis of bone loss in elderly men is still incomplete. We previously demonstrated that the age-related increase in serum PTH contributes substantially to the increased bone resorption in elderly women, since suppression of PTH levels by an intravenous calcium infusion decreased bone resorption markers to a greater extent in elderly compared to premenopausal women. In the present study, we tested the hypothesis that the comparable increase in PTH levels in elderly men (age 70-78 years) was driving bone resorption to a greater extent in these men than in younger men (age 40-50 years). PTH secretion was suppressed by an intravenous calcium infusion and the corresponding changes in the bone resorption marker, urine N-telopeptide of type I collagen (NTx) were assessed. In contrast to our previous findings in pre- versus postmenopausal women, suppression of PTH secretion in elderly men did not result in a greater decrease in urine NTx excretion than in the younger men (change in NTx excretion in the elderly men, -2.79+/-1.99 nmol/mmol Cr, versus that in the younger men, -5.07+/-1.39 nmol/mmol Cr, P=0.356). Collectively, these data suggest that the relationship between the age-related increase in serum PTH levels and bone resorption differs between elderly men and women. Since both estrogen and testosterone can attenuate the bone resorbing effects of PTH, it is possible that this difference may be due to the much milder degree of sex steroid deficiency in elderly men as compared to postmenopausal women.

Adult↗

PubMed2003

CTLA4 is associated with susceptibility to multiple sclerosis.

We comprehensively screened CTLA4 for novel genetic variations in patients with MS. We studied genetic variations by association methods in a population-based sample of 122 sporadic patients with MS and 244 age-, gender- and ethnicity-matched controls, and by linkage and family-based association methods in 395 individuals from 59 American multiplex pedigrees with 141 affected individuals. Being homozygous for AT(8) (common) allele of the 3'(514) microsatellite (OR: 1.69; CI: 0.99-2.86) and for the common 5'(318)*C/E1(49)*A/3'(514*AT(8) haplotype (OR: 1.96; CI: 1.13-3.39) was associated with increased susceptibility to MS in Olmsted County. The genotype frequencies of other individual polymorphisms were not significantly different between cases and controls. A pooled analysis of association studies revealed an odds ratio of 1.28 (95% CI: 1.01-1.63; p=0.043) for 5'(-318)*C homozygotes and 1.28 (95% CI: 1.08-1.51; p=0.005) for the 3'(514)*AT(8) allele. We did not detect linkage with MS susceptibility in multiplex families. We did not find a strong association with age at onset, disease course or severity. CTLA-4 is associated with susceptibility to MS.

Abatacept↗

PubMed2003

A population-based study of IL4 polymorphisms in multiple sclerosis.

Previous studies have suggested a role for interleukin-4 gene (IL4) in susceptibility to multiple sclerosis (MS) as well as other autoimmune diseases. We screened the promoter region, exons 1-4 and their splice sites for polymorphisms and tested the association between novel polymorphisms E1(33)*C-->T and I3(2580)*C-->A, and the established 5'(-523)*C-->T and I3(709)*VNTR polymorphisms with susceptibility to, age of onset in, and course and severity of MS in sporadic cases. I3(709)*VNTR was associated with susceptibility to MS (p=0.004) due to a dearth of heterozygotes in patients (29/122; 23.8%) compared to controls (91/244; 37.3%). Homozygotes for the uncommon I3(709)*allele-2 may have increased susceptibility (p=0.044; OR=5.17, 95% CI: 0.83-54.95) as might carriers for the extended haplotypes 5'(-523)*T/E1(33)*T/I3(709)*allele-2/I3(2580)*C (p=0.003; OR: 3.75, 95% CI: 1.18-11.93) or 5'(-523)*C/E1(33)*C/I3(709)*allele-1/I3(2580)*A (p=0.004; OR: 4.22, 95% CI: 1.22-14.54). We could not confirm the previously reported association between carriage of I3(709)*allele-2 and older age of onset. However, we found a trend for association between the homozygous state for this allele and older age of onset.

Adult↗

PubMed2003

Risk of fracture in ulcerative colitis: a population-based study from Olmsted County, Minnesota.

BACKGROUND & AIMS: Osteopenia is common in patients with ulcerative colitis (UC), but less is known about fracture risk. Previously we were unable to demonstrate increased fractures in a population-based cohort with Crohn's disease. METHODS: Medical records of 273 Olmsted County, Minnesota residents initially diagnosed with UC in 1940-1993 were reviewed for evidence of subsequent fractures, as were records of a control cohort of county residents matched on age and gender. Cumulative fracture incidence after diagnosis was estimated by using the Kaplan-Meier method. The hazard ratio of fracture in cases relative to control subjects was estimated by Cox proportional hazards regression, which was also used to evaluate potential risk factors for fracture. RESULTS: Median follow-up was 13 years (range, 1 day-53 years). The cumulative incidence of any fracture from time of diagnosis was 40% at 25 years versus 42% in control subjects (P=0.615). The hazard ratio in cases compared to control subjects was 1.1 (95% confidence interval, 0.8-1.6) for any fracture and 1.3 (95% confidence interval, 0.6-2.8) for any osteoporotic fracture (hip, spine, or wrist as a result of moderate trauma). Other causes of secondary osteoporosis were associated with increased fracture risk, whereas estrogen use was protective. One hundred three cases received any corticosteroids (38%), and 34 (12%) had taken corticosteroids for 6 months or longer. Corticosteroids and bowel resection were not associated with fracture risk. CONCLUSIONS: In this population-based cohort of patients with UC, fracture risk was not elevated relative to matched community control subjects. Use of corticosteroids did not appear to significantly influence the risk of fracture.

Adolescent↗

PubMed2003

Fracture risk following bilateral orchiectomy.

PURPOSE: Bone loss has been reported in patients with prostate cancer treated with androgen deprivation therapy. We assess fracture risk following bilateral orchiectomy. MATERIALS AND METHODS: Through the Rochester Epidemiology Project we identified 429 Olmsted County, Minnesota men who underwent bilateral orchiectomy in 1956 to 2000, almost all for prostate cancer. Fractures were ascertained from comprehensive medical records and compared with expected numbers based on local incidence rates (standardized incidence ratio, SIR). Potential risk factors were assessed with proportional hazards models. RESULTS: During 1961 person-years of followup 161 men experienced 267 fractures, for a cumulative incidence after 15 years of 40% compared to 19% expected (p <0.001). However, 42 were pathological fractures and 82 were found incidentally on radiological surveys for metastasis. Overall fracture risk was increased (SIR 3.42, 95% CI 2.91-3.99) but was reduced by excluding the pathological and incidental fractures (SIR 2.04, 95% CI 1.66-2.47). The increase was largely accounted for by the moderate trauma fractures of the hip, spine and distal forearm traditionally linked with osteoporosis (SIR 3.50, 95% CI 2.71-4.43). In multivariate analyses risk factors for fractures generally included patient age, inactivity, prior radiological diagnosis of osteoporosis, chemotherapy and use of nonsteroidal antiandrogens, while independent risk factors for the traditional osteoporotic fractures included age, inactivity and diagnosis of osteoporosis. CONCLUSIONS: Fractures are common in men with prostate cancer due to advanced age, occurrence of pathological fractures and enhanced skeletal surveillance but there remains a significant increase in osteoporotic fracture risk following bilateral orchiectomy.

Adult↗

PubMed2003

Fracture risk after bilateral oophorectomy in elderly women.

Elderly women with the lowest serum estrogen levels are at the greatest risk of bone loss and fractures, but it is controversial whether the ovaries contribute to estrogen production after menopause, and therefore, whether bilateral oophorectomy in postmenopausal women might have adverse skeletal effects. To address this potential problem, we estimated long-term fracture risk among 340 postmenopausal Olmsted County, MN, women who underwent bilateral oophorectomy for a benign ovarian condition in 1950-1987. In over 5632 person-years of follow-up (median, 16 years per subject), 194 women experienced 516 fractures (72% from moderate trauma). Compared with expected rates, there was a significant increase in the risk of any osteoporotic fracture (moderate trauma fractures of the hip, spine, or distal forearm; standardized incidence ratio [SIR], 1.54; 95% CI, 1.29-1.82) but almost as large an increase in fractures at other sites (SIR, 1.35; 95% CI, 1.13-1.59). In multivariate analyses, the independent predictors of overall fracture risk were age, anticonvulsant or anticoagulant use for > or = 6 months, and a history of alcoholism or prior osteoporotic fracture; obesity was protective. Estrogen replacement therapy was associated with a 10% reduction in overall fracture risk (hazard ratio [HR], 0.90; 95% CI, 0.64-1.28) and a 20% reduction in osteoporotic fractures (HR, 0.80; 95% CI, 0.52-1.23), but neither was statistically significant. The increase in fracture risk among women who underwent bilateral oophorectomy after natural menopause is consistent with the hypothesis that androgens produced by the postmenopausal ovary are important for endogenous estrogen production that protects against fractures.

Adult↗

PubMed2003

Risk of breast cancer and breast cancer characteristics in women treated with supradiaphragmatic radiation for Hodgkin lymphoma: Mayo Clinic experience.

OBJECTIVE: To evaluate the overall risk of breast cancer and breast cancer characteristics in women given supradiaphragmatic radiation therapy for Hodgkin lymphoma. PATIENTS AND METHODS: Medical records of 653 female patients who received supradiaphragmatic radiation therapy for Hodgkin lymphoma at the Mayo Clinic in Rochester, Minn, between 1950 and 1993 were abstracted, and follow-up questionnaires were mailed. In 4 patients, breast cancer was diagnosed before Hodgkin lymphoma was discovered. RESULTS: The median age of 649 patients at supradiaphragmatic radiation therapy was 31.8 years (range, 2.6-86.5 years). The median duration of follow-up was 8.7 years (range, < 1-47.9 years). In 30 patients, breast cancer developed (bilaterally in 4 patients) after supradiaphragmatic radiation therapy; the median interval was 19.9 years (range, 0.7-423 years). The median age at breast cancer diagnosis was 44.4 years (range, 27.5-70.8 years). The standardized morbidity ratio for breast cancer after supradiaphragmatic radiation therapy was 2.9 (95 % confidence interval [CI], 2.0-4.2) (P < .001). Breast cancer risk significantly increased 15 to 30 years after patients received supradiaphragmatic radiation therapy, and risk was inversely related to age at supradiaphragmatic radiation therapy until age 30 years. The standardized morbidity ratio for patients younger than 30 years at supradiaphragmatic radiation was 8.5 (95% CI, 53-13.1) vs 1.2 (95% CI, 0.5-2.2) for those aged 30 years or older (P < .001). Splenectomy increased breast cancer risk (P = .01). Breast cancer detection was by self-examination in 15 cancers, by mammography in 13, and by clinical examination in 4; in 2 cancers, the mode of detection was unknown. Modified radical mastectomy was used to treat breast cancer. CONCLUSION: The increased risk of breast cancer in survivors of Hodgkin lymphoma given supradiaphragmatic radiation therapy appears to be limited to patients who are younger than 30 years at radiation therapy or to those who have undergone splenectomy.

Adult↗

PubMedDate not supplied

Effects of duration of type 2 diabetes mellitus on insulin secretion.

OBJECTIVE: To gain insight into the effects of duration of type 2 diabetes on insulin secretion in patients with type 2 diabetes mellitus. METHODS: C-peptide concentrations were measured every 2 years before and after intravenous injection of 1 mg of glucagon in 89 patients with type 2 diabetes (51 men and 38 women) as part of the Rochester Diabetic Neuropathy Study in those subjects who participated in follow-up (median, 12 years; range, 6 to 14). RESULTS: Although insulin secretion decreased over time (P<0.001) in the group as a whole, both the pattern and the rate of decline in C-peptide concentration differed considerably among the study subjects. Insulin secretion, whether measured as fasting C-peptide, 6-minute C-peptide, or postglucagon increment in C-peptide concentrations, declined with increasing duration of diabetes in approximately half of the patients but either increased or remained essentially constant over time in the other half. The decrease in insulin secretion was not associated with a deterioration in glycemic control because hemoglobin A1c also declined (P<0.005) during the same interval. CONCLUSION: We conclude that insulin secretion decreases over time in many patients with type 2 diabetes. Because the rate of decline is variable, the predictive value of any single measurement is limited. These data indicate that although a decrease in insulin secretion over time is characteristic of type 2 diabetes mellitus, it is not inevitable.

Blood Glucose↗