Search

Objectives To determine dosing patterns and examine predictors of filled hydroxychloroquine (HCQ) prescriptions in patients with systemic lupus erythematosus (SLE) with end-stage renal disease (ESRD). Methods This was a retrospective cohort study of patients with SLE in the US Renal Data System (USRDS) database in fiscal year 2011. All patients were Medicare Part D beneficiaries. Patients with a diagnosis of SLE were identified by the International Classification of Diseases, 9th revision code 710. The prevalence, dosing, and predictors of filled HCQ prescriptions (demographic factors, dialysis type, and provider subspecialty) were determined. Results There were 10,276 patients with SLE identified; 2048 (19.9%) had a prescription for HCQ filled. The mean daily dose of HCQ was 321 mg (range 58–2000 mg). The most common daily doses were 200 (n=768, 37.5%) and 400 mg (n=1161, 56.7%). In multivariable logistic regression analysis, significant predictors of filled HCQ prescriptions included black/African-American race (OR 1.34, 95% CI (1.17 to 1.46)), hemodialysis (1.50, 95% CI (1.29 to 1.74)), and care from a rheumatologist (5.06, 95% CI (4.56 to 5.62)). Negative predictors of filled HCQ prescriptions included male gender (OR 0.72, 95% CI (0.63 to 0.83)) and those aged 45 years or older (compared to 20 years old and younger, aged 45–64 years, OR 0.66, 95% CI (0.54 to 0.79); aged 65–74 years, OR 0.58, 95% CI (0.44 to 0.76); aged 75 years and older, OR 0.56, 95% CI (0.39 to 0.82)). Conclusions In patients with SLE with ESRD, the dosing strategies for HCQ with regard to potential toxicity and disparities in prescribing patterns need further study.

Background We investigated the effects of demographic, lifestyle (self-reported smoking status and physical activity levels), cancer-related treatment factors (radiation and chemotherapy), and diet (calcium and vitamin D intake) on bone turnover and the relationship of bone turnover to lumbar spine bone mineral density (BMD) Z-scores (LS-BMD Z-scores) determined by Quantitative Computed Tomography (QCT) in 418 ≥5-year survivors of childhood acute lymphoblastic leukemia (ALL).

In the United States, there are over 200,000 men with spinal cord injuries (SCIs) who are at risk for lower limb fractures. The risk of mortality after fractures in SCI is unknown. This was a population-based, cohort study of all male veterans (mean age 54.1; range, 20.3-100.5 years) with a traumatic SCI of at least 2 years' duration enrolled in the Veterans Affairs (VA) Spinal Cord Dysfunction Registry from FY2002 to FY2010 to determine the association between lower extremity fractures and mortality. Mortality for up to 5 years was determined. The lower extremity fracture rate was 2.14 per 100 patient-years at risk for at least one fracture. In unadjusted models and in models adjusted for demographic, SCI-related factors, healthcare use, and comorbidities, there was a significant association between incident lower extremity fracture and increased mortality (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; HR, 1.36; 95% CI, 1.15-1.61, respectively). In complete SCI, the hazard of death after lower extremity fracture was also increased (unadjusted model: HR, 1.46; 95% CI, 1.13-1.89; adjusted model: HR, 1.32; 95% CI, 1.02-1.71). In fully-adjusted models, the association of incident lower extremity fracture with increased mortality was substantially greater in older men (age ≥50 years) for the entire cohort (HR, 3.42; 95% CI, 2.75-4.25) and for those with complete SCI (HR, 3.13; 95% CI, 2.19-4.45), compared to younger men (age

Background We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation.

To identify circumstances surrounding incident lower extremity fractures (ILEFs) in patients with spinal cord injury (SCI) and to describe the impact of these fractures on service needs and provision of pharmacological therapies for osteoporosis.Retrospective medical record review.Four Veterans Affairs Medical Centers in the USA.One hundred and forty patients with traumatic SCI who sustained an ILEF from 2002 to 2007.Fracture circumstances and use of assistive devices were described using percentages, means, and standard deviations. Fisher's exact test was used to determine the relationship between fracture site, and patient age and duration of SCI. Differences in pharmacological provision of therapies for osteoporosis pre- and post-fracture were examined using exact McNemar's test.One hundred and fifty-five ILEFs were identified in 140 patients. Tibia/fibula and femur fractures were the most common fractures. Fracture site was not related to patient's age or duration of SCI. Almost one-third of all fractures occurred during transfers to and from wheelchairs. Post-fracture, the provision of new or modified assistive devices, primarily wheelchairs, was frequent, occurring in 83% of patients in the year post-fracture. Few patients transferred residence to a nursing home following the fracture. There was a significant difference in the use of pharmacological therapies for osteoporosis in the first year post-fracture compared with the year prior to the fracture (P0.01), with significant differences in the volume of prescriptions for calcium supplements (P0.01) and bisphosphonates (P = 0.02). Overall, the amount of prescriptions for osteoporosis increased the year post-fracture (56%) from the year pre-fracture (39%); this increase was secondary to increases in prescriptions for calcium supplements (pre = 13%; post = 30%) and bisphosphonates (pre = 2%; post = 7%).We have identified that wheelchair and other transfer activities are a key area that could be a focus of fracture prevention in SCI. The need for new or modified assistive devices and/or wheelchair skills retraining post-fracture should be anticipated. Examination of whether treatments for osteoporosis following a fracture can prevent future osteoporotic fractures is warranted.

Context: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis. Objective: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults. Design and Setting: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease. Participants: Participants included 2008 women and 1329 men ≥65 years from the 1996 to 1997 Cardiovascular Health Study visit. Main Outcome Measures: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants. Results: Women had higher plasma FGF23 concentrations than men (75 [56–107] vs 66 [interquartile range = 52–92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001–0.04 g/cm2, and 0.03 with 95% CI = 0.01–0.06 g/cm2). During 9.6 ± 5.1–11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95% CI = 0.78–1.15, and 1.09 with 95% CI = 0.82–1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions). Conclusions: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.

Objective Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. Methods A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. Results At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. Conclusions The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways.

ObjectivesTo identify factors that predicted incident use of assistive walking devices (AWDs) and to explore whether AWD use was associated with changes in osteoarthritis of the knee.DesignProspective cohort study.SettingCommunity.ParticipantsOlder adults (N=2639) in the Health, Aging and Body Composition (Health ABC) Study including a subset of 874 patients with prevalent knee pain.InterventionsNot applicable.Main outcome measuresIncident use of AWDs, mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores, and the frequency of joint space narrowing on knee radiographs over a 3-year time period.ResultsAWD use was initiated by 9% of the entire Health ABC cohort and 12% of the knee pain subset. Factors that predicted use in both groups were age ≥73 (entire cohort: odds ratio [OR]=2.07; 95% confidence interval [CI], 1.43-3.01; knee pain subset: OR=1.87; 95% CI, 1.16-3.03), black race (entire cohort: OR=2.95; 95% CI, 2.09-4.16; knee pain subset: OR=3.21; 95% CI, 2.01-5.11), and lower balance ratios (entire cohort: OR=3.18; 95% CI, 2.21-4.59; knee pain subset: OR=3.77; 95% CI, 2.34-6.07). Mean WOMAC pain scores decreased slightly over time in both AWD and non-AWD users. Twenty percent of non-AWD users and 28% of AWD users had radiographic progression in joint space narrowing of the tibiofemoral joint in at least 1 knee. Fourteen percent of non-AWD users and 12% of AWD users had radiographic progression in joint space narrowing in the patellofemoral joint in at least 1 knee.ConclusionsAWDs are frequently used by older adults. Knee pain and balance problems are significant reasons why older adults initiate use of an AWD. In an exploratory analysis, there was no consistent relation between the use or nonuse of an AWD and WOMAC pain scores or knee joint space narrowing progression. Further studies of the relation of use of AWDs to changes in knee osteoarthritis are needed.

Background: Previous literature has shown a strong negative effect of angiotensin II (ANGII) on bone metabolism within mouse models. Additionally, psychological stress has been associated with activation of the renin-angiotensin-aldosterone system (RAAS). Stress has also been related to lower total bone mineral density (TBMD). However, there is controversy in the literature examining the relationship between the RAAS and bone metabolism within humans and stress has not been considered as a direct link between these systems. Purpose: We aimed to examine the relationship between stress-induced RAAS activation and TBMD and total bone mineral content (TBMC). Methods: Participants were placed on a sodium controlled diet for three days. Participants then underwent two hours rest, one hour mental stressor, and two hours recovery with hourly collections of blood/urine samples. Renin, ANGII, aldosterone, TBMD and TBMC were measured. Results: This study recruited 586 adolescents (mean age 16±1.116) with 51% women and 62% African-American and 38% Caucasian. Overall, relationships were observed between ANGII and aldosterone, and TBMC and TBMD controlling for age, race, and BMI. During stress, aldosterone was related to TBMD (r=-.150, p Conclusion/Interpretations: These data suggest that stress-induced RAAS activation may be associated with lower TBMD and TBMC in girls. Despite small correlations, consistency across multiple measures of RAAS activation being apparent in adolescents is significant. This observation may indicate that stress activation of RAAS contributes to bone remodeling in early life.

The purpose of this study was to characterize etiologies of spinal cord injury and disorders (SCI/D) in persons with and without cervical stenosis/spondylosis (CSS) and to describe clinical characteristics and underlying comorbidities in these populations.We reviewed administrative data for 1954 Veterans who had onset of traumatic or non-traumatic tetraplegia during FY 1999-2007. This included 1037 with a diagnosis of CSS at or in the two years prior to SCI onset of SCI/D and 917 without a diagnosis of CSS.Demographics, etiologies of SCI/D and comorbidities by CSS status.Veterans with SCI/D and CSS were older, more likely to have incomplete injuries and more likely to be Black than those with SCI/D and no CSS. Of patients with traumatic etiologies for SCI, 35.1% had a diagnosis of CSS at the time of or in the 2 years prior to SCI onset. Of those with tetraplegia due to falls, 40.0% had CSS, whereas for other known traumatic etiologies the percentages with CSS were lower: vehicular (25.0%); sports (16.1%); and acts of violence (10.2%). Total comorbidity scores measured by the Charlson co morbidity index and CMS Hierarchical Condition Category (CMS-HCC) were higher in those with CSS and SCI/D compared to those with SCI/D without CSS (P 0.0001 respectively).CSS is commonly present in patients with new traumatic tetraplegia. Falls are a particularly important potentially modifiable risk for SCI in patients with CSS.

Although heart failure (HF) and osteoporosis are common diseases, particularly in elderly populations, patients with HF have an increased risk for osteoporosis. The relationship of HF with osteoporosis is modified by gender and the severity of HF. In addition, shared risk factors, medication use, and common pathogenic mechanisms affect both HF and osteoporosis. Shared risk factors for these 2 conditions include advanced age, hypovitaminosis D, renal disease, and diabetes mellitus. Medications used to treat HF, including spironolactone, thiazide diuretics, nitric oxide donors, and aspirin, may protect against osteoporosis. In contrast, loop diuretics may make osteoporosis worse. HF and osteoporosis appear to share common pathogenic mechanisms, including activation of the renin-angiotensin-aldosterone system, increased parathyroid hormone levels, and/or oxidative/nitrosative stress. HF is a major risk factor for mortality following fractures. Thus, in HF patients, it is important to carefully assess osteoporosis and take measures to reduce the risk of osteoporotic fractures.

Osteoarthritis (OA) of the knee is a major cause of disability among the elderly (1–3), and its prevalence is projected to grow substantially with the aging of the U.S. population (2,4). Despite the high prevalence of this condition and the high personal and economic impact of osteoarthritis-related disability, there are currently no specific therapies that can prevent the onset or progression of joint damage caused by OA. Medical therapies designed to control pain and swelling can be associated with side effects, and the withdrawal of certain COX-2 inhibitors from the market due to safety concerns has further limited therapeutic options (5). With limited therapeutic modalities and concerns about long-term safety of existing modalities, it is imperative to better understand the physiological and biological relationships underlying knee OA in order to devise and promote better preventive and therapeutic options. Muscle weakness, and in particular quadriceps weakness, has been implicated in knee OA and quadriceps strengthening exercises are a therapeutic approach recommended by some experts (6–9). However, reports on the relationship between muscle strength and knee OA have presented conflicting data, due in part, perhaps, to an emphasis on gross measurements of strength that do not adequately control for other intrinsic muscle properties. A generalized loss of skeletal muscle mass with aging, known as sarcopenia, contributes to muscle weakness. In OA patients as well as in aging, the decrement in strength is greater than would be expected for reduction in size of the muscle (10). This suggests that alterations in the intrinsic characteristics of muscle, reflecting a diminished muscle quality, may also contribute to impaired muscle function of the elderly and of those with knee OA. However, there is little information concerning the association of skeletal muscle composition with the prevalence of OA. Lower limb muscle composition and quality is likely related to overall body composition, and obesity has also been implicated as a risk factor for OA, particularly in women (10,11). Many patients with knee OA are obese, and will be stronger than those who are less obese because they have a higher muscle mass as part of a higher total mass. Strength is highly correlated with lean or muscle mass (12). Thus, strength differences in those with and without OA cannot be adequately examined without adjusting for lean mass. One of the most intruiging reports relating body composition and muscle strength to knee OA was that of Slemenda and colleagues (10), who showed that reduced quadriceps strength relative to body weight and lean muscle mass (measured by Dual Energy X-ray Absorptiometry (DXA)) was a risk factor for development of knee OA in women. These results suggest that the quality of muscle is impaired; however, there has been little recent literature to follow-up or confirm these provocative findings. A more recent report by Sharma and colleagues (14) suggested that in some cases greater quadriceps strength may be associated with higher risk of progressive knee OA in patients with greater laxity in their knee. Unfortunately, this study did not include any measures of muscle mass or composition and controlled for body composition only through BMI. However, these results emphasize that the relationship of muscle strength and knee OA may be modified by other factors. Advanced imaging techniques such as computed tomography (CT) can be used to give accurate estimates of lower extremity muscle mass. Lower extremity strength per unit muscle mass, or specific torque, is a measure of muscle quality. In addition, CT can be used to measure muscle attenuation, suggestive of an increased muscle fat content (15), is a marker of muscle quality that contributes to muscle weakness independent of the age-associated loss in muscle mass (16). In the current study, we examined the association of radiographic and symptomatic knee OA with muscle strength, muscle area, intermuscular fat infiltration, and muscle quality using CT in a large, biracial cohort of elderly participants. We hypothesized that both radiographic and symptomatic knee OA would be associated with poorer muscle quality and higher muscle fat content.

The relationship between anti-TNF therapy and development of lymphoma in Rheumatoid arthritis (RA) patients is controversial. However lymphomas of unusual types and sites have been reported among RA patients receiving anti-TNF therapy. Primary lymphoma of the breast is a rare entity and has never been reported to occur among RA patients taking anti-TNF therapy. This is the first case of primary lymphoma of the breast reported among RA patients on anti-TNF therapy. Rheumatoid arthritis patients currently on anti-TNF therapy should undergo routine gynecological examination.

Objectives. SSc (scleroderma) is an often fatal disease characterized by widespread tissue fibrosis. Fibroblasts play a key role in SSc-associated fibrosis. This study was designed to determine: (i) whether fibroblasts isolated from skin of patients with SSc have increased lysophosphatidic acid-activated Cl - current (ICI LPA ) activity vs healthy controls; (ii) whether myofibroblast differentiation is involved in SSc skin fibrosis; and (iii) whether SSc fibroblasts have different proliferation rates vs controls. Methods. Skin biopsies were taken from involved and uninvolved skin of SSc patients and controls. Whole-cell perforated patch-clamping was used to measure ICI LPA activity in fibroblasts isolated and cultured from these biopsies. Western blotting was used to measure α-smooth muscle actin (α-SMA). Proliferation was measured using a colorimetric assay. Results. Fibroblasts cultured from SSc skin show significantly increased ICI LPA activity following LPA exposure compared with control skin fibroblasts. α-SMA protein was significantly increased in cultured SSc skin fibroblasts vs controls. No significant differences in proliferation rates were found. Conclusions. Elevated ICI LPA activity is a hallmark of SSc skin fibroblasts. Blocking ICI LPA activation may be a new therapeutic approach for treating SSc-associated fibrosis.

Using national Medicare data from 1999-2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices.Medicare reimbursement for DXAs performed in non-facility settings (e.g., physician offices) decreased in 2007. With declining reimbursement, some DXA providers may cease providing this service, which would increase travel distance for some people. The impact of travel distance on access to DXA is unclear.Using national Medicare data, we identified claims for DXA to evaluate trends in the number and locations of DXAs performed. Travel distance was the distance from beneficiaries' residence and the nearest DXA provider. Binomial regression evaluated the relationship between travel distance and receipt of DXA.In 2006, 2.9 million DXAs were performed, a 103% increase since 1999. In 2005-2006, 8.0% of persons were tested at non-facility sites versus 4.2% at facility sites. The remainder (88%) had no DXA. Persons traveling 5-9, 10-24, 25-39, and 40-54, andor = 55 miles were less likely to receive DXA (adjusted risk ratios = 0.92, 0.79, 0.43, 0.32, and 0.26, respectively,5 miles referent). Rural residents were more dependent than urban residents on the availability of DXA from non-facility providers.Approximately two-thirds of DXAs in 2005-2006 were performed in non-facility settings (e.g., physician offices). Rural residents would have preferentially reduced access to DXA if there were fewer non-facility sites.

The BONEII study is a large two-phase study. The baseline study (Study 1) aims to estimate the prevalence of diminished bone mineral density (BMD) in patients treated for childhood acute lymphoblastic leukemia (ALL) and identify risk factors for BMD deficits. The interventional phase (Study 2) of BONEII has a placebo-controlled double-blind randomized longitudinal design to evaluate the effects of nutritional counseling and calcium and vitamin D supplementation on changes in BMD and serum and urine markers of bone metabolism. The extensive information being collected through this large study will serve as a repository of relational data about BMD and bone turnover and will support further investigations to assess the association of calcium metabolism, bone turnover, nutritional intake, lifestyle factors (such as exercise and the use of alcohol and tobacco), and the specific agents used in ALL therapy in this rapidly increasing population of childhood cancer survivors.

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.

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

As a consequence of cost-cutting changes, termed "TennCare reform," to Tennessee's state-funded health care plan, a number of beneficiaries have either had their benefits substantially reduced or have been disenrolled entirely. The purpose of this study was to determine the impact of these reforms on the health of patients with chronic rheumatic diseases.We determined differences with adherence to scheduled appointments in an urban academic rheumatology clinic in the 3 months before and in the 3 months after TennCare reform. A telephone survey was conducted to determine plans for future rheumatic care among those patients scheduled to be seen in this clinic in the 3 months after TennCare reform.Overall, 402 of the 601 patients scheduled for a rheumatology clinic appointment before TennCare reform (67%) adhered to their scheduled rheumatology appointment, compared with 362 of 595 patients (61%) scheduled for an appointment after TennCare reform, a difference that was statistically significant (P = 0.034). After TennCare reform, patients who did not adhere with clinic follow-up were more likely to have been disenrolled from TennCare (P0.001). By telephone survey, among those who were disenrolled from TennCare, almost half indicated that they did not know where they were going to receive future rheumatic disease care. Among those who retained TennCare, less than half indicated that they could afford to purchase all of their medications.TennCare reform has significantly limited care for patients with rheumatic diseases. The long-term consequences of this merit future study.

Factors contributing to heart failure (HF) in African Americans (AA) are under investigation. Reduced 25(OH)D confers increased cardiovascular risk, including HF.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 ofor=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).Serum 25(OH)Dor=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)D30 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 PTH65 pg/mL was found in all AA with decompensated HF ofor=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.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.

Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture. Few studies to date have comprehensively addressed clinical risk factors for fracture in persons with spinal cord injury (SCI). The purpose of this study was to identify risk factors for incident osteoporotic fractures in persons with a SCI that can be easily determined at the point of care. The Veteran’s Affairs Spinal Cord Dysfunction Registry, a national database of persons with a SCI, was used to examine clinical and SCI-related risk factors for fracture. Incident fractures were identified in a cohort of persons with chronic SCI, defined as SCI present for at least 2 years. Cox regression models were used to estimate the risk of incident fractures. There were 22,516 persons with chronic SCI included in the cohort with 3365 incident fractures. The mean observational follow-up time for the overall sample was 6.2 years (median 6.0, IQR 2.9–11.0). The mean observational follow-up time for the fracture group was 3.9 years (median 3.3, IQR 1.4–6.1) and 6.7 years (median 6.7, IQR 3.1–11.0) for the nonfracture group. By the end of the study, which included predominantly older Veterans with a SCI observed for a relatively short period of time, the absolute (i.e., cumulative hazard) for incident fractures was 0.17 (95%CI 0.14–0.21). In multivariable analysis, factors associated with an increased risk of fracture included White race, traumatic etiology of SCI, paraplegia, complete extent of SCI, longer duration of SCI, use of anticonvulsants and opioids, prevalent fractures, and higher Charlson Comorbidity Indices. Women aged 50 and older were also at higher risk of sustaining an incident fracture at any time during the 11-year follow-up period. There are multiple clinical and SCI-related risk factors which can be used to predict fracture in persons with a SCI. Clinicians should be particularly concerned about incident fracture risk in persons with a SCI who have had a previous fracture.

The objective of this study was to evaluate the role of serum levels of 25(OH)D and PTH on the accumulation of whole body bone mass in a cohort of children.This was a longitudinal study (1.98 +/- 0.07 y) of sixty-nine children (89% Caucasian, 44% male) enrolled in a calcium supplementation trial. Bone area, bone mineral content (BMC) and density (BMD) of the whole body and radius were assessed using a QDR 2000 (Hologic, Inc) dual energy x-ray absorptiometer. Serum PTH and 25(OH)D were measured using radioimmunoassays.Vitamin D stores were inversely related gain in bone area (p0.002), BMC (p0.002) BMD (p0.027), as well as to PTH levels (p0.0001). Compared to those with adequate vitamin D stores (34 ng/ml), those who had consistently low vitamin D stores (18 ng/ml) had a 8% larger gain in bone area (p0.05); 11% in BMC (p0.05) and no differences in gain in BMD; after adjusting for baseline bone measurements, race, gender, season measured, Tanner stage, and calcium intake.High normal PTH with low-normal 25(OH)D stores and moderate to high calcium intake may be beneficial to accruing larger bone size and BMC during puberty.

Heart failure is thought to be more common and of greater severity in African-Americans (AAs). Potential mechanisms remain uncertain. The importance of micronutrient deficiencies in the pathophysiologic expression of congestive heart failure (CHF) in AAs remains to be explored, including hypovitaminosis D, which can promote secondary hyperparathyroidism (SHPT), together with hypozincemia and hyposelenemia, the 2 most crucial trace minerals integral to diverse biologic functions. Serum parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), Zn, and Se were monitored in 30 AAs hospitalized during June through December 2005, with decompensated failure and reduced ejection fraction (EF) (35%) of predominantly nonischemic origin treated with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), furosemide, and spironolactone. Based on their symptomatic status before hospitalization, 15 patients were stratified as having protracted (or=4 weeks) CHF, whereas 15 patients had short-term (1-2 weeks) CHF. These hospitalized patients were compared with 10 AA outpatients with stable, similarly treated compensated failure and comparable EF, and 9 AA normal volunteers without cardiovascular disease. Serum PTH was elevated in all patients with protracted CHF and in 60% of patients with short-term CHF, but not in compensated patients or normal volunteers. However, serum 25(OH)D was reduced in all patients withor=4 weeks and 80% with either 1-2 weeks CHF or compensated failure compared with volunteers. Serum Zn was below normal in 11 of 15 patients with protracted CHF, in 8 of 15 patients with shorter duration CHF, and in 5 of 10 patients with compensated failure. Serum Se was reduced in all patients withor=4 weeks, 60% with short-term CHF, and 90% of compensated patients. Concomitant to hypovitaminosis D, hypozincemia, and hyposelenemia, SHPT is a covariant of CHF in housebound AAs.

Summary A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-γ, interleukin (IL)-10, transforming growth factor (TGF)-β1, tumour necrosis factor (TNF)-α and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-γ and TNF-α and reduced levels of TGF-β1 for up to 24 weeks after the infusion. γδ T cells from patients with SSc were activated in vitro and produced increased IFN-γ. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study.

An emerging body of evidence suggests secondary hyperparathyroidism (SHPT) may be an important covariant of congestive heart failure (CHF), especially in African-Americans (AA) where hypovitaminosis D is prevalent given that melanin, a natural sunscreen, mandates prolonged exposure of skin to sunlight and where a housebound lifestyle imposed by symptomatic CHF limits outdoor activities and hence sunlight exposure. In addition to the role of hypovitaminosis D in contributing to SHPT is the increased urinary and fecal losses of macronutrients Ca(2+) and Mg(2+) associated with the aldosteronism of CHF and their heightened urinary losses with furosemide treatment of CHF. Thus, a precarious Ca(2+) balance seen with reduced serum 25(OH)D is further compromised when AA develop CHF with circulating RAAS activation and are then treated with a loop diuretic. SHPT accounts for a paradoxical Ca(2+) overloading of diverse tissues and the induction of oxidative stress at these sites which spills over to the systemic circulation. In addition to SHPT, hypozincemia and hyposelenemia have been found in AA with compensated and decompensated heart failure and where an insufficiency of these micronutrients may have its origins in inadequate dietary intake, altered rates of absorption or excretion and/or tissue redistribution, and treatment with an ACE inhibitor or AT(1) receptor antagonist. Zn and Se deficiencies, which compromise the activity of several endogenous antioxidant defenses, could prove contributory to the severity of heart failure and its progressive nature. These findings call into question the need for nutriceutical treatment of heart failure and which is complementary to today's pharmaceuticals, especially in AA.

INTRODUCTIONThe skeletal health of the rapidly growing population ofsurvivors of childhood cancer may be compromised by theeffects of disease and therapy [1–3]. Maximal peak bonemass, an important determinant of osteoporosis and fractureassociated with aging, may not be achieved. In normalindividuals, bone mass rises rapidly during puberty [4] andusually reaches its peak at the end of sexual development.Therefore,childrenwhoundergocancertreatmentduringthenormal period of maximal bone-mass accrual are at risk forfuture deficits in bone mineral density (BMD) and itssequelae. Consequently, an accurate and consistent assess-ment of bone mass in this population is important. Theleading methods of assessing BMD are quantitative com-puted tomography (QCT) and dual X-ray absorptiometry(DXA), although DXA is more widely used [3,4]. Bothmethods are used clinically sometimes in the same patient,making it difficult to interpret longitudinal changes in BMDand assess treatment efficacy.We tested the relationship between BMD values obtainedusing both DXA and QCT in the same young patients. Bothmethods provide rapid assessment; each has strengths andweaknesses. For the reason that DXA BMD assessmentdepends partially on bone size, its use in growing children isespecially challenging [3–6]. With both methods, clinicaltreatment decisions in pediatrics typically are based onstandard deviation or Z-scores, which, despite their limita-tions, allow comparison of individual BMD values to age-and sex-matched normative values. DXA also defines bonemineral status by comparing to race-matched references.Bone mineral density values determined by QCT inchildren are volumetric and independent of bone size [3,4].QCT also can differentiate trabecular from cortical bone,providing additional information regarding bone health.Affordable QCT software can be installed on most CTscanners, but the initial cost of CT scanners and support stafflimits its availability.Dual X-ray absorptiometry is available worldwide andcan assess the BMD of thewhole body or ofindividual areas.This two-dimensional method produces values of ‘‘areal’’BMD; changes in the third dimension are not accountedfor, which leads to underestimation of BMD of smallersized bones by DXA. This disadvantage is an important

The purposes of this study were to determine, by state, the requirements for dual-energy X-ray absorptiometry(DXA) operators' training, knowledge of these state requirements, and factors that predicted state and International Society of Clinical Densitometry (ISCD) certification of DXA technologists. Seventeen states required registered technologist (RT) certification or authorized/licensed limited certification for DXA operators, 16 had no certification requirements, 12 required RT certification, and 5 had state-specific requirements. There were 9745 surveys mailed toDXA users including 50% Hologic Inc., 50% GE Lunar, and 100% Norland; 3148 surveys are included in this analysis. Among responders who indicated that their state did not have any certification requirements (n=1673), 1095(65.5%) were incorrect; there were requirements. Possession of state and ISCD certification was significantly correlated with the number of patients scanned per week (por=0.05), the number of technologists employed within a center (p0.01), and the subspecialty of the practitioner (por=0.02). Our study uncovered a lack of uniformity amongstates with respect to central DXA operator training requirements. Additionally, in those states with requirements, DXA operators were often unaware of these requirements. Uniform national training requirements for central DXA operators to ensure adequate DXA scan quality are urgently needed.

Objective To examine the cross-sectional association between use of medications that have a bone antiresorptive effect (estrogen, raloxifene, and alendronate) and both the structural features of knee osteoarthritis (OA), assessed by magnetic resonance imaging (MRI) and radiography, and the symptoms of knee OA in elderly women. Methods Women in the Health, Aging and Body Composition Study underwent MRI and radiography of the knee if they reported symptoms of knee OA, and women without significant knee symptoms were selected as controls. MR images of the knee were assessed for multiple features of OA using the Whole-Organ MRI scoring method, and radiographs were read for Kellgren and Lawrence grade and individual features of OA. Concurrent medication use and knee symptoms were assessed by interview, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results There were 818 postmenopausal women from whom we obtained MR images of the knee and data on medication use. Among these women, 214 (26.2%) were receiving antiresorptive drugs. We found no significant association between overall use of antiresorptive drugs and the presence of knee pain and radiographic changes of OA of the knee. Use of alendronate, but not estrogen, was associated with less severity of knee pain as assessed by WOMAC scores. Both alendronate use and estrogen use were associated with significantly less subchondral bone attrition and bone marrow edema–like abnormalities in the knee as assessed by MRI, as compared with women who had not received these medications. Conclusion Elderly women being treated with alendronate and estrogen had a significantly decreased prevalence of knee OA–related subchondral bone lesions compared with those reporting no use of these medications. Alendronate use was also associated with a reduction in knee pain according to the WOMAC scores.

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. Introduction: The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway. Materials and Methods: NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men; 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of >1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of

Background: An increasing number of studies have examined the use of information technology to improve diabetes care and patient self-management. The goal of the current study was to determine the number of veterans seen for diabetes at a large medical center in the southeastern region of the U.S. and to examine whether they had registered for VA’s My HealtheVet patient web portal according to selected characteristics. Methods: Existing patient records were reviewed including My HealtheVet web portal registration by veterans treated for diabetes (ICD-10 code for type 2 diabetes) at the Charlie Norwood VAMC. Number of outpatient clinic patients seen for diabetes who had or had not registered for My HealtheVet were examined by age categories, sex, race, Hispanic ethnicity, and era of military service. Results: A total of 49,341 veterans receive care at the Charlie Norwood VAMC. Of those patients, 10,950 have been seen for diabetes. Of the 49,341 patients, 21,372 patients (43.3%) are using My HealtheVet and 10,465 patients (21.2%) have used secure messages. Of 10,950 diabetic patients, only 1,256 (11.5%) have registered for My HealtheVet. Women with diabetes were more likely to be registered for My HealtheVet than their male counterparts [13.92% vs. 11.24%; odds ratio (OR)=1.28; 95% confidence interval (CI): 1.05–1.55). Veterans with diabetes who served during WW II or the Korean War were less likely to use My HealtheVet than those who served during more recent eras (OR=0.33; 95% CI: 0.24–0.44). Use of the patient portal was highest among diabetic patients ages 51–55 years (15.6%). Conclusions: A low percentage of Veterans with diabetes are active users of My HealtheVet. Studies are needed to identify My HealtheVet portal design features and veteran characteristics that will increase use of this patient portal which may improve diabetes care.

Ehlers-Danlos Syndrome (EDS) is the most common inherited disorder of connective tissue recognized. The objectives of the present study were to determine bone mineral density (BMD) and biochemical markers of bone metabolism in EDS. Twenty-three subjects with Type III EDS and 23 matched controls underwent BMD measurement by dual-Energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. Health history questionnaires and biochemical markers of bone and connective tissue metabolism were also assessed. No significant differences in BMD at the lumbar spine or differences in biochemical markers of bone and connective tissue metabolism were found between EDS subjects and controls. EDS subjects had a significantly decreased BMD at the femoral neck compared with controls, but this difference disappeared after adjustment for body height, weight and physical activity levels.

WITH SURVIVAL RATES for childhood cancers now approaching 70%, there is an urgent need to assess the nature, prevalence, and risk factors for long-term treatment sequelae. Survival rates for pediatric malignancies increased from 20% in 1965 to 66% in 1995. As a result, it is anticipated that by the year 2000, 1 in every 900 individuals between the ages of 15 and 45 years will be a survivor of childhood cancer. This growing population of long-term childhood cancer survivors represents a new group at risk for early onset osteoporosis. Adverse late effects resulting from impaired bone mineral density (BMD) (i.e., increased risk of early onset osteoporosis, fracture, and other bone defects) have been observed in cohorts of childhood cancer survivors of several primary tumor types. The frequency of diminished lumbar spine BMD has ranged from 8–23% of survivors who received chemotherapy prior to physeal closure. The wide range of reported frequencies probably reflects the study of relatively small numbers of patients with diverse primary tumor types and treatments. The imprecise information about the prevalence, risk factors for, and treatment approaches for diminished BMD in pediatric patients further emphasizes the need for prospective study in these patients.

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.

This study investigated whether there were differences in quantitative ultrasound (QUS) of the calcaneus between African-American and Caucasian females. QUS-1X TM , an ultrasonometer by Metra Biosystems Inc., was used to determine broadband ultrasound attenuation (UBI-4) using Burg Spectral Estimation in decibels/megahertz. The average transit time through the heel (TTH) in microseconds was used to estimate bone size. A multiple factor index taking into account bone size, UBI-4T, was calculated by dividing UBI-4 by TTH in decibels/(Megahertz-microseconds). Results showed that premenopausal Caucasian females ( n = 37) have approx 6-8% lower values ( p n = 54) counterparts. However, after adjusting for bone size, the differences in attenuation disappeared. Pilot data for males (Caucasian: n = 16, African-American: n = 18) suggest that the differences in QUS appear to be related to bone size. The limited scope of our study supports the fact that there are differences in QUS between premenopausal Caucasian and African-American females, but not with the same magnitude as evidenced by dual X-ray absorptiometry. We recommend that more data be collected on ethnic differences across all age ranges, to help understand how QUS may be used to assess bone mass and determine its value either as a screening tool to diagnose low bone mass or as a tool to predict osteoporotic fracture within various ethnic groups.

We investigated the effects of demographic, lifestyle (self-reported smoking status and physical activity levels), cancer-related treatment factors (radiation and chemotherapy), and diet (calcium and vitamin D intake) on bone turnover and the relationship of bone turnover to lumbar spine bone mineral density (BMD) Z-scores (LS-BMD Z-scores) determined by quantitative computed tomography (QCT) in 418 ≥5-year survivors of childhood acute lymphoblastic leukemia (ALL).Bone turnover was assessed by biomarkers including serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), and urinary N-telopeptide of type I collagen indexed to creatinine (NTX/Cr). The 215 males ranged in age from 9 to 36 years (median age 17 years).Age and tanner score were inversely associated with all biomarkers (BALP, OC, NTX/Cr) (P 0.001). Males had higher BALP and OC than females (P 0.001). Body mass index (BMI) was inversely associated with OC and NTX/Cr (P 0.001). There was no significant association of biomarkers with lifestyle related factors, ALL treatment-related factors, dietary calcium, vitamin D, or LS-BMD Z-score.In this population of long-term survivors of ALL, bone turnover was significantly associated with age, gender, tanner stage, and BMI. ALL-related treatments did not influence bone turnover and bone turnover was not predictive of volumetric LS-BMD Z-score.

Traditional assessments of bone properties have utilized densitometry techniques such as Dual Energy X-ray Absorptiometry (DXA). Recently, quantitative ultrasound (QUS) has been introduced as an alternative method of assessing bone properties. Advantages of QUS over X-ray techniques include low costs, portability, and nonionizing radiation. Proponents of QUS have claimed that this technology can provide information not only about the density but also about the structure and mechanical properties of bone. There are two major questions that need to be answered for those who seek to diagnose bone disorders with ultrasound: (1) what does quantitative ultrasound actually measure, and, even more importantly, (2) what is its clinical utility? In this review we will briefly examine the first question and will focus on the utility of ultrasound in clinical trials to discriminate between fractures and non-fractures and to predict the risk of fractures. J Am Geriatr Soc 45:1382–1394, 1997.

Epidemiological studies of the association of sodium and potassium intake with cardiovascular disease risk have almost exclusively relied on self-reported dietary data. Here, 24-hour urinary excretion assessments are used to correct the dietary self-report data for measurement error under the assumption that 24-hour urine recovery provides a biomarker that differs from usual intake according to a classical measurement model. Under this assumption, dietary self-reports underestimate sodium by 0% to 15%, overestimate potassium by 8% to 15%, and underestimate sodium/potassium ratio by ≈20% using food frequency questionnaires, 4-day food records, or three 24-hour dietary recalls in Women’s Health Initiative studies. Calibration equations are developed by linear regression of log-transformed 24-hour urine assessments on corresponding log-transformed self-report assessments and several study subject characteristics. For each self-report method, the calibration equations turned out to depend on race and age and strongly on body mass index. After adjustment for temporal variation, calibration equations using food records or recalls explained 45% to 50% of the variation in (log-transformed) 24-hour urine assessments for sodium, 60% to 70% of the variation for potassium, and 55% to 60% of the variation for sodium/potassium ratio. These equations may be suitable for use in epidemiological disease association studies among postmenopausal women. The corresponding signals from food frequency questionnaire data were weak, but calibration equations for the ratios of sodium and potassium/total energy explained ≈35%, 50%, and 45% of log-biomarker variation for sodium, potassium, and their ratio, respectively, after the adjustment for temporal biomarker variation and may be suitable for cautious use in epidemiological studies. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00000611.

OBJECTIVE: The aim of this study was to determine whether anticonvulsants, including the benzodiazepine subclass, are associated with an increased risk for lower extremity fractures in male patients with spinal cord injury. DESIGN: All male patients with a history of a traumatic spinal cord injury of 2 yrs' duration or longer in the Veterans Affairs Spinal Cord Disease Registry from 2002 to 2007 were included. Incident lower extremity fractures during this period and anticonvulsant use were identified. The association of anticonvulsant use, overall, by type (enzyme inducing, non-enzyme inducing), by number (monotherapy vs. polytherapy), by benzodiazepine subclass, and by individual medication used was determined. RESULTS: In this cohort, 892 veterans sustained a fracture, and 6555 did not. Compared with nonusers of anticonvulsants, there was a significant positive relationship with fractures by overall use of anticonvulsants (HR, 1.17 [95% CI, 1.01-1.36]), by users of the benzodiazepine subclass (HR, 1.28 [95% CI, 1.11-1.47]), and by polytherapy compared with monotherapy (HR, 1.20 [95% CI, 1.00-1.42]) but not by anticonvulsant type (HR, 0.92 [95% CI, 0.58-1.47]). Temazepam (HR, 1.28 [95% CI, 1.01-1.62]), alprazolam (HR, 1.54 [95% CI, 1.04-2.29]), and diazepam (HR, 1.23 [95% CI, 1.06-1.41]) were significantly positively associated with fractures. CONCLUSIONS: Attention to fracture prevention is important when anticonvulsants are prescribed in spinal cord injury, particularly when more than one anticonvulsant is used. Language: en

This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT).This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women's Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density.Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density.Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.

The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men.The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (30 mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78 years.From the Cardiovascular Health Study (41 % male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5 years. BMD was performed in a subset of 1,208 participants.There were 313 hip fractures during follow-up (7.7 % of men; 11.7 % of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95 % CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009 g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women.In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

To determine the association between opioid use and lower extremity fracture risk in men with spinal cord injury (SCI).Retrospective cohort study.Veterans Affairs Healthcare System.In total, 7447 male Veterans with a history of a traumatic SCI identified from the Veterans Affairs (VA) Spinal Cord Dysfunction Registry (SCD) from September 2002 through October 2007 and followed through October 2010.Incident lower extremity fractures by use of opioids.In individuals identified from the VA SCD Registry 2002-2007, opioid use was quite common, with approximately 70% of the cohort having received a prescription for an opioid. Overall, there were 892 incident lower extremity fractures over the time period of this study (597 fractures in the opioid users and 295 fractures in the non-opioid users). After adjusting for covariates, there was a statistically significant relationship between opioid use and increased risk for lower extremity fractures (hazard ratio 1.82 (95% confidence interval 1.59-2.09)). Shorter duration of use (6 months) and higher doses were positively related to fracture risk (P0.0001).Opioid use is quite common in SCI and is associated with an increased risk for lower extremity fractures. Careful attention to fracture prevention is warranted in patients with SCI, particularly upon initiation of an opioid prescription and when higher doses are used.

In the United States, there are over 200,000 men with spinal cord injuries (SCIs) who are at risk for lower limb fractures. The risk of mortality after fractures in SCI is unknown. This was a population-based, cohort study of all male veterans (mean age 54.1; range, 20.3-100.5 years) with a traumatic SCI of at least 2 years' duration enrolled in the Veterans Affairs (VA) Spinal Cord Dysfunction Registry from FY2002 to FY2010 to determine the association between lower extremity fractures and mortality. Mortality for up to 5 years was determined. The lower extremity fracture rate was 2.14 per 100 patient-years at risk for at least one fracture. In unadjusted models and in models adjusted for demographic, SCI-related factors, healthcare use, and comorbidities, there was a significant association between incident lower extremity fracture and increased mortality (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; HR, 1.36; 95% CI, 1.15-1.61, respectively). In complete SCI, the hazard of death after lower extremity fracture was also increased (unadjusted model: HR, 1.46; 95% CI, 1.13-1.89; adjusted model: HR, 1.32; 95% CI, 1.02-1.71). In fully-adjusted models, the association of incident lower extremity fracture with increased mortality was substantially greater in older men (age ≥50 years) for the entire cohort (HR, 3.42; 95% CI, 2.75-4.25) and for those with complete SCI (HR, 3.13; 95% CI, 2.19-4.45), compared to younger men (age50 years) (entire cohort: HR, 1.42; 95% CI, 0.94-2.14; complete SCI: HR, 1.71; 95% CI, 0.98-3.01). Every additional point in the Charlson comorbidity index was associated with a 10% increase in the hazard of death in models involving the entire cohort (HR, 1.11; 95% CI, 1.09-1.13) and also in models limited to men with complete SCI (HR, 1.10; 95% CI, 1.06-1.15). These data support the concept that both the fracture itself and underlying comorbidities are drivers of death in men with SCI.

Importance Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. Objective To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. Design, Setting, and Participants Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women’s Health Initiative (WHI) observational study. Participants in the prospective cohort included 93 676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. Main Outcomes and Measures Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. Results Of the 93 676 participants, 90 014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28 718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. Conclusions and Relevance Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.

Background Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse. Objective To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Women's Health Initiative randomized, placebo-controlled, clinical trial. Design In post hoc analyses, the results of the Women's Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups. Results At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [ P =0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [ P =0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P =0.02). Conclusions Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms.

The Veterans Affairs Spinal Cord Dysfunction Registry from 2002 to 2007 was reviewed to determine whether men with spinal cord injury (SCI) and lower extremity fractures had an increased risk of complications compared to those without fractures. We determined that fractures are associated with significant consequences, particularly during the first month postfracture.Despite increasing longevity, patients with SCI have a substantial number of illnesses and comorbid conditions. Lower extremity fractures are frequent events in these patients. However, whether these fractures are associated with any increased risk of complications in SCI is not certain. The purpose of this report was to determine the impact of lower extremity fractures on morbidities in men with SCI.A population-based, nested, case-control (1,027 cases and 1,027 propensity-matched controls) of men enrolled in the Veterans Affairs Spinal Cord Dysfunction Registry from fiscal years 2002 to 2007 was reviewed to determine whether lower extremity fractures were associated with an increased risk for complications.In propensity score models matched for demographic (age, race) and SCI-related injury factors (level/completeness of SCI), Veterans Affairs-service connection status, and comorbidities, at 1 month following the fracture, there was an increased risk for respiratory infections, pressure ulcers, urinary tract infections, thromboembolic events, depression, and delirium (p ≤ 0.03 for all). Over 12 months, the only complication more common in fracture cases was pressure ulcers (p 0.01), with an absolute difference of less than 2 % when compared to controls. There was no significant increased risk of cardiac arrhythmias at any time examined following fracture (≥0.12).Lower extremity fractures are associated with significant consequences in men with SCI during the first month postfracture, but they do not persist for a long term, except for pressure ulcers. Targeted interventions to prevent complications should be considered following lower extremity fractures in SCI, particularly in the first month following fracture.