Laura D. Carbone

Association Between Bone Mineral Density and the Use of Nonsteroidal Anti‐Inflammatory Drugs and Aspirin: Impact of Cyclooxygenase Selectivity

BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX‐2 selective NSAIDs with aspirin (COX‐2/ASA) compared with nonusers. This suggests a role for COX‐2/ASA in osteoporosis.

Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults

BACKGROUND Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture. METHODS Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline. RESULTS During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women. CONCLUSIONS Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

Longitudinal Trends in Use of Bone Mass Measurement Among Older Americans, 1999–2005

Bone mass measurement (BMM) is useful to identify persons with low bone mass who are at increased risk for fracture. Given the increased emphasis that is being placed on preventive services such as screening for osteoporosis, we evaluated trends in BMM among Medicare beneficiaries. We studied a 5% sample of Medicare beneficiaries ≥65 yr of age in 1999–2005. We identified claims for BMM tests performed in both facility and nonfacility settings, evaluated temporal trends in use of these tests, and described the proportion of tests attributable to each specialty of physicians submitting claims. We also assessed patterns of serial testing among individuals who were tested more than once. Claims data from all years were pooled to describe the proportion of persons in the population ever tested. From 1999 to 2005, use of central DXA increased by ∼50%, and use of peripheral DXA declined. The greatest increases in central DXA occurred among internists, family practitioners, and gynecologists. In 1999, the proportion of 65‐yr‐old women tested was 8.4%; this increased to 12.9% in 2005. Corresponding proportions for men were 0.6% and 1.7%, respectively. Between 40% and 73% of persons receiving central DXA were retested, most at ∼2‐yr intervals. Aggregating data across all years for whites and blacks, 30.0% of women and 4.4% of men underwent central DXA at least once. We conclude that, although use of DXA steadily increased from 1999 to 2005, only ∼30% of women and 4% of men at least 65 yr old had a central DXA study. Given the importance of central DXA to assess the risk of osteoporotic fractures, strategies to increase central DXA use to test at‐risk persons are warranted.

LACK OF EFFICACY OF ORAL BOVINE TYPE II COLLAGEN ADDED TO EXISTING THERAPY IN RHEUMATOID ARTHRITIS

OBJECTIVE To investigate the efficacy of oral type II collagen (CII) in the treatment of rheumatoid arthritis (RA), when added to existing therapy. METHODS Patients with active RA (n = 190) were randomized into a 6-month, double-blind, placebo-controlled trial. Patients continued to take their current arthritis medications. Patients received either placebo or bovine CII, 0.1 mg/day for 1 month, then 0.5 mg/day for 5 months. RESULTS There were no significant differences between the baseline characteristics of either group. The primary response parameter was the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20). There was no statistically significant difference in the ACR 20 after 6 months (20.0% of placebo patients; 16.84% of bovine CII patients). There were significant differences in several clinical variables after treatment, all favoring the placebo group. CONCLUSION Oral solubilized bovine CII, added to existing therapy, did not improve disease activity in patients with RA.

25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation

Vitamin D deficiency may have implications for cardiovascular health. The purpose of this study was to determine the relationship of 25-hydroxyvitamin D (25[OH]D) to cholesterol and lipoprotein particles and to determine whether increasing 25(OH)D through ultraviolet (UV) irradiation impacted on these parameters in healthy young men and women. This was a randomized trial of 51 adults exposed to suberythemal doses of whole-body irradiation using UV lamps that emitted UV-A and UV-B radiation, compared with a control group, twice weekly for 12 weeks. 25-Hydroxyvitamin D, cholesterol, and lipoprotein subfractions were measured at baseline and after 12 weeks. There was a significant (P < .03) positive association between 25(OH)D and apolipoprotein A-I (Apo A-I) and lipoprotein A-I (Lp A-I). The ratio of low-density lipoprotein to high-density lipoprotein was significantly (P < or = .044) negatively correlated with 25(OH)D levels. The levels of 25(OH)D increased significantly in the treated compared with control group (P < .05). Overall, there were no significant differences between the treated and control groups in any lipoproteins or apolipoproteins after administration of UV irradiation. Subgroup analysis for Apo A-II confined to those with 25(OH)D insufficiency (25[OH]D <75 nmol/L [30 ng/mL]) revealed decreases in Apo A-II in the treated group and increases in the control group that were statistically significantly different between the groups (P = .026). We found a significant positive correlation between 25(OH)D and Apo A-I and Lp A-I and a significant negative correlation between 25(OH)D and the ratio of low-density lipoprotein to high-density lipoprotein. In those with vitamin D insufficiency, we found small decreases in Apo A-II in the treated relative to the control group. Overall, though, twice weekly exposure to UV radiation resulting in an increase in serum 25(OH)D had no significant impact on lipoprotein composition.

Fracture Risk in Men With Congestive Heart Failure: Risk Reduction With Spironolactone

OBJECTIVES The purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF). BACKGROUND In rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known. METHODS The medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of having a fracture associated with spironolactone use were estimated using conditional logistic regression. RESULTS We identified 167 cases with a single-incident fracture and matched these by age and race to 668 control subjects without fractures. After adjustment for covariates, spironolactone use was inversely associated with total fracture (odds ratio: 0.575; 95% confidence interval: 0.346 to 0.955, p = 0.0324). CONCLUSIONS The use of spironolactone is inversely associated with fractures in men with CHF.

Hypovitaminosis D in African Americans residing in Memphis, Tennessee with and without heart failure

Background:Factors contributing to heart failure (HF) in African Americans (AA) are under investigation. Reduced 25(OH)D confers increased cardiovascular risk, including HF. Methods:We monitored serum 25(OH)D, 1,25(OH)2D3, parathyroid hormone (PTH), and creatinine clearance in 102 AA residing in Memphis: 58 hospitalized with decompensated HF of ≥4 weeks in 34 (21 men; 53.3 ± 1.8 years) or of 1 to 2 weeks in 24 (17 men; 49.6 ± 2.4 years) and associated with a dilated cardiomyopathy and reduced ejection fraction (<35%); 19 outpatients with compensated HF (14 men; 52.6 ± 2.7 years) with comparable ejection fraction; 16 outpatients (9 men; 55.4 ± 2.9 years) with heart disease, but without HF; and 9 healthy volunteers (3 men; 35.8 ± 3.5 years). Results:Serum 25(OH)D ≤30 ng/mL was found in 96% and 90% with protracted or short-term decompensated HF, where it was of moderate to marked severity (<20 ng/mL) in 83% and 76%, respectively. In patients with either compensated or no HF, 25(OH)D <30 ng/mL was found in 95% and 100%, respectively, and in 30% of volunteers. Normal serum 1,25(OH)2D3 did not differ between patients. Serum PTH >65 pg/mL was found in all AA with decompensated HF of ≥4 weeks (132.4 ± 12.0 pg/mL) and 67% with 1 to 2 weeks duration (82.3 ± 7.9 pg/mL), but only 11% with compensated HF (45.8 ± 6.1 pg/mL), 12% without HF (29.6 ± 5.4 pg/mL), and none of the volunteers (31.1 ± 3.9 pg/mL). Creatinine clearance did not differ between patient groups. Conclusions:Hypovitaminosis D is prevalent amongst AA residing in Memphis, with or without HF. Elevations in serum PTH in keeping with secondary hyperparathyroidism are only found in AA with decompensated HF, where hypovitaminosis D and other factors are contributory.

Hip fractures and heart failure: findings from the Cardiovascular Health Study

AIMS The aim of the study was to find the epidemiology of hip fractures in heart failure. The increasing survival rate for patients with heart failure places them at risk for other diseases of ageing, including osteoporosis. METHODS AND RESULTS We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95% CI 1.2-2.93) and 1.59 (95% CI 0.93-2.72), respectively. Respective HRs for women were 1.75 (95% CI 1.27-2.4) and 1.41 (95% CI 0.98-2.03). Mortality hazard was approximately 2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone. CONCLUSION Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure.

Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: Findings from the Women's Health Initiative (WHI)

Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a number of conditions. However, the relationship between the use of these medications, particularly the newer AEDs, and fracture risk has not been well characterized. We used data from the Womens Health Initiative (WHI) to determine the relationship bewteen the use of AEDs and falls, fractures, and bone mineral density (BMD) over an average of 7.7 years of follow‐up. We included 138,667 women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this longitudinal cohort analyses. After adjustment for covariates, use of AEDs was positively associated with total fractures [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.30–1.61], all site‐specific fractures including the hip (HR = 1.51, 95% CI 1.05–2.17), clinical vertebral fractures (HR = 1.60, 95% CI 1.20–2.12), lower arm or wrist fractures (HR = 1.40, 95% CI 1.11–1.76), and other clinical fractures (HR = 1.46, 95% CI 1.29–1.65) and two or more falls (HR = 1.62, 95% CI 1.50–1.74) but not with baseline BMD or changes in BMD (p ≥ .064 for all sites). Use of more than one and use of enzyme‐inducing AEDs were significantly associated with total fractures (HR = 1.55, 95% CI 1.15–2.09 and HR = 1.36, 95% CI 1.09–1.69, respectively). We conclude that in clinical practice, postmenopausal women who use AEDs should be considered at increased risk for fracture, and attention to fall prevention may be particularly important in these women.

Muscle strength, mass, and quality in older men and women with knee osteoarthritis

To examine the relationship between knee osteoarthritis (OA) and muscle parameters in a biracial cohort of older adults.