Citations

To determine comparative rates of development and progression of peripheral occlusive arterial disease, 110 healthy nondiabetic control subjects, 112 patients with peripheral occlusive arterial disease (POAD), 240 patients with diabetes mellitus (DM), and 100 patientswith diabetes mellitus and peripheral occlusive arterialdisease (DM + POAD) were studied over 4 yr with noninvasive techniques. The presence of peripheral occlusive arterial disease was determined by postexercise ankle-brachial index (ABI) values; progression of peripheral occlusive arterial disease was determined by the rate of change in postexercise ABI. Patients who underwent peripheral arterial reconstructive surgery or amputation were also classified as having progression of their peripheral occlusive arterial disease. On this basis, follow-up revealed that peripheral occlusive arterial disease developed and therefore progressed in 1 (1%) of the control group and 22 (9%) of the DM. Peripheral occlusive arterial disease progressed in 31 (28%) of the POAD and 26 (26%) of the DM + POAD. The presence of peripheral occlusive arterial disease predisposes to progression of disease, and peripheral occlusive arterial disease is more likely to develop in diabetic patients who do not have peripheral occlusive arterial disease than in nondiabetic control subjects. However, the presence of diabetes mellitus in patients with peripheral occlusive arterial disease does not seem to increase the risk of progression.

Background: The relative risk of cardiovascular disease (CVD) associated with diabetes is greater for women than men, and diabetic women did not experience temporal declines in CVD mortality observed for the general population and diabetic men. Objective: To examine sex differences in CVD risk factors for persons with diabetes over time. Design: Population-based historical cohort study. Methods: The provider-linked medical records of all Rochester, MN, residents assigned a clinical diagnosis of diabetes were reviewed to confirm case status and assign diagnosis date. Data on fasting glucose, obesity, persistent proteinuria, smoking, hypertension, and dyslipidemia were obtained at diagnosis for confirmed incidence cases. Results: There were 1330 diabetes cases 1970–1989. Compared to men, women at diagnosis were older and more likely hypertensive, had similar levels of fasting glucose and persistent proteinuria, and less likely to smoke. Among persons diagnosed at younger ages, women were more likely than men to be obese. Comparison with published data for the Rochester population revealed the excess obesity and hypertension associated with diabetes were highest for women < age 55 y. Temporal trends in CVD risk factors did not differ between diabetic men and women.

Abstract Long-term fracture prediction using bone mineral density remains controversial, as does the additional contribution from assessing bone turnover or clinical risk factors. We measured bone mineral density at various sites, along with biochemical markers of bone turnover, sex steroid levels, and over 100 clinical variables, at baseline on an age-stratified sample of 304 Rochester, MN women in 1980. The 225 postmenopausal women were subsequently followed for 3146 person-years (median, 16.2 years per subject), wherein they experienced 302 new fractures: 81% resulted from minimal or moderate trauma and 60% of these involved the proximal femur, thoracic or lumbar vertebrae, or distal forearm. Accounting for multiple fractures per subject, these osteoporotic fractures together were best predicted by baseline femoral neck bone mineral density (age-adjusted hazard ratio [HR] per SD decrease, 1.37; 95% CI, 1.10–1.70); 19 moderate trauma forearm fractures were best predicted by distal radius bone mineral content, whereas 28 hip fractures and 100 vertebral fractures were best predicted by femoral neck bone mineral density. Femoral neck bone mineral density performed comparably in predicting osteoporotic fracture risk within the first decade of follow-up (HR, 1.38; 95% CI, 1.10–1.74) as well as more than 10 years after baseline (HR, 1.39; 95% CI, 1.05–1.84). The older biochemical markers were not associated with fractures, but serum “free” estradiol index was independently predictive of short- and long-term fracture risk. Consistent clinical risk factors were not identified, but statistical power was limited. Identifying patients at increased long-term risk of fracture is challenging, but it is reassuring that femoral neck bone mineral density can predict osteoporotic fractures up to 20 years later.

Abstract Although median levels of bone turnover are increased in postmenopausal women, it is unclear whether the low circulating levels of endogenous estrogen exert a regulatory role on these levels. This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age ± SD, 69 ± 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months. Letrozole treatment reduced serum estrone (E1) and estradiol (E2) to near undetectable levels (p &lt; 0.0001). This treatment did not affect bone formation markers but, as compared with the placebo group, increased bone resorption markers (urine 24-h pyridinoline [PYD] by 13.3% [p &lt; 0.05] and 24-h urine deoxypyridinoline [DPD] by 14.2% [p &lt; 0.05]) and decreased serum parathyroid hormone (PTH) by 22% (p = 0.002). These data indicate that in late postmenopausal women even the low serum estrogen levels present exert a restraining effect on bone turnover and support the concept that variations in these low levels may contribute to differences in their rate of bone loss.

Abstract Localized disruption of bone architecture leads to an increased risk of pathological fractures in patients with Paget's disease, but the impact of the disease on overall fracture risk is unknown. We addressed this issue among 236 Olmsted County, Minnesota residents (107 women and 129 men) first diagnosed with Paget's disease from 1950 through 1994. These subjects (mean ± SD age at diagnosis, 69.6 ± 12.2 years) were followed subsequently for 2798 person-years. During this period of observation, 33 pathological fractures were attributed to Paget's disease (1 skull, 11 vertebra, 1 shaft/distal humerus, 1 pelvis, 6 proximal femur, 2 shaft/distal femur, and 11 tibia/fibula). Excluding the fractures through pagetic bone, there was no increase in overall fracture risk in this cohort (standardized incidence ratio [SIR], 1.2; 95% CI, 0.9-1.4). However, there was a statistically significant increase in the risk of subsequent vertebra (SIR, 3.0; 95% CI, 2.2-4.1) and rib fractures (SIR, 1.7; 95% CI, 1.1-2.4) but not fractures of the proximal femur (SIR, 0.6; 95% CI, 0.3-1.1) or distal forearm (SIR, 1.4; 95% CI, 0.7-2.5). Thus, unselected patients with Paget's disease in the community, who mostly have mild disease, have a significantly increased risk of vertebral fractures, although this may relate partly to increased surveillance. Additional work is needed to clarify the relationship between Paget's disease and vertebral fractures and to identify individuals at increased risk for more aggressive therapy.

Abstract An age-stratified sample of 304 women from Rochester, Minnesota, aged 30–94 years (median 60 years) at baseline underwent measurement of femoral neck bone mineral density (BMD) over a follow-up period extending to 16 years. The average rate of change in femoral neck BMD was −1.0% per year (range −10.0% to +13.4%) and did not vary significantly with age. Because there was no marked increase in the rate of loss around the time of menopause, nor convincing evidence of there being a subset of fast losers, there was fairly good tracking of individual values over time; the correlation of baseline with femoral neck BMD values 16 years later was 0.83. Although a large number of potential determinants was assessed, the only consistent predictor of femoral neck bone loss in women of different ages was baseline femoral neck BMD (r = −0.15; p = 0.023). Otherwise, different sets of risk factors were identified for premenopausal women, women within 20 years of menopause, and women 20 years or more postmenopausal, but the predictive power of these different multivariate models was modest. Nonetheless, these data indicate that femoral neck BMD is quite predictable for extended periods of time. This is reassuring with respect to the use of statistical models that incorporate such data to estimate future fracture risk.

Abstract We report a 4-year randomized, double-blind, placebo-controlled clinical trial in 236 normal postmenopausal women (mean age ± SE, 66.3 ± 0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p &lt; 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: −18.9% (p = 0.002) for parathyroid hormone (PTH), −11.9% (p = 0.026) for serum osteocalcin, and −32.2% (p = 0.003) for urine free pyridinoline. We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Abstract Bone mass is purportedly reduced by an endogenous or exogenous excess of thyroid hormone or, perhaps, by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects, yet their practical implications in terms of fracture risk are poorly defined. Interpretation is further hampered by the focus on women, where results may be influenced by involutional osteoporosis. Consequently, we assessed the potential for fractures among the 136 Rochester, Minnesota men who underwent thyroidectomy between 1935 and 1979, relative to a group of age-matched control men from the community. With 2194 person-years of follow-up in each group, survival free of any fracture of vertebra, proximal humerus, distal forearm, pelvis, or proximal femur was similar in the two groups (p = 0.23), and the relative risk of any of these fractures for thyroidectomized patients versus their controls was increased only 1.5-fold (95% CI, 0.7–3.2). The difference was entirely accounted for by a statistically significant excess of proximal femur fractures in the men with thyroidectomy. Risk factors for fractures among men with thyroidectomy included greater age at surgery, greater extent of surgery, and the presence of risk factors for secondary osteoporosis. Thus, thyroidectomy, performed mainly for adenoma or goiter, seems to have little overall influence on the risk of age-related fractures in men. However, the association with hip fractures requires further evaluation.

Abstract To assess the influence of bone turnover on bone density and fracture risk, we measured serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal propeptide of type I procollagen (PICP), as well as 24-h urine levels of cross-linked N-telopeptides of type I collagen (NTx) and the free pyridinium cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), among 351 subjects recruited from an age-stratified random sample of Rochester, Minnesota women. PICP, NTx, and Dpd were negatively associated with age among the 138 premenopausal women. All of the biochemical markers were positively associated with age among the 213 postmenopausal women, and the prevalence of elevated turnover (&gt;1 standard deviation [SD] above the premenopausal mean) varied from 9% (PICP) to 42% (Pyd). After adjusting for age, most of the markers were negatively correlated with bone mineral density (BMD) of the hip, spine, or forearm as measured by dual-energy X-ray absorptiometry, and women with osteoporosis were more likely to have high bone turnover. A history of osteoporotic fractures of the hip, spine, or distal forearm was associated with reduced hip BMD and with elevated Pyd. After adjusting for lower BMD and increased bone resorption, reduced bone formation as assessed by OC was also associated with prior osteoporotic fractures. These data indicate that a substantial subset of elderly women has elevated bone turnover, which appears to adversely influence BMD and fracture risk. Combined biochemical and BMD screening may provide better prediction of future fracture risk than BMD alone.