Monique Bethel

End-stage renal disease in patients with rheumatoid arthritis.

OBJECTIVES To determine the frequency of end-stage renal disease (ESRD) in patients with rheumatoid arthritis (RA), the causes of ESRD, and the treatment of RA in the setting of ESRD. METHODS Cross-sectional study of RA (N = 3754) and non-RA (N = 326,776) patients in the United States Renal Data System (USRDS) during 2011 (N = 330,530). The epidemiology of ESRD in RA was determined and the etiology of ESRD in patients with and without RA was compared. The frequency of patients with RA with at least one filled prescription for prednisone/prednisolone, a DMARD, and/or a biologic in 2011 was determined. RESULTS The prevalence of RA with ESRD in the USRDS in 2011 was 1.1%. There were significant differences in age, race, sex, and BMI category between the groups (p < 0.01). Diabetes (33.5%) and hypertension (30.6%) were the most common primary causes of ESRD in patients with RA. Amyloidosis, vasculitis, and analgesic nephropathy combined accounted for less than 10% of cases of ESRD. Prednisone was the most commonly filled medication that could be used to treat RA (45.9% of RA patients). Hydroxychloroquine was the most frequently filled DMARD (13.5%); biologics were uncommon (etanercept 2.5%, adalimumab 1.5%; golimumab, infliximab, anakinra, and abatacept <1%). CONCLUSIONS The co-occurrence of RA with ESRD was 1.1% in the USRDS by 2011. Physicians should be aware of the critical impact of the comorbidities of diabetes and hypertension in causing ESRD in RA patients. Use of DMARDS other than hydroxychloroquine and biologics to treat RA in the setting of ESRD appears to be infrequent. Further prospective studies of treatment strategies for RA in ESRD are needed.

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative.

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Womens Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis.

Sodium Intake and Osteoporosis. Findings From the Women's Health Initiative.

In this large, prospective, observational cohort study of postmenopausal women in the WHI, Cox proportional hazard regression models showed that sodium intake at or near recommended levels is not likely to impact bone metabolism.

Association of Plasma SDF-1 with Bone Mineral Density, Body Composition, and Hip Fractures in Older Adults: The Cardiovascular Health Study

Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures. In 1536 CHS participants, SDF-1 plasma levels were significantly associated with increasing age (p < 0.01) and male gender (p = 0.04), but not with race (p = 0.63). In multivariable-adjusted models, higher SDF-1 levels were associated with lower total hip BMD (p = 0.02). However, there was no significant association of SDF-1 with hip fractures (p = 0.53). In summary, circulating plasma levels of SDF-1 are associated with increasing age and independently associated with lower total hip BMD in both men and women. These findings suggest that SDF-1 levels are linked to bone homeostasis.

A historical study of appendicular fractures in veterans with traumatic chronic spinal cord injury: 2002-2007.

Objective: Describe the incidence and distribution of appendicular fractures in a cohort of veterans with spinal cord injury (SCI). Design: Retrospective, observational study of fractures in veterans with a chronic traumatic SCI. Setting: The Veterans Health Administration (VA) healthcare system. Participants: Veterans included in the VA Spinal Cord Dysfunction Registry from Fiscal Years (FY) FY2002–FY2007. Interventions: Not applicable. Main Outcome Measures: Description of fractures by site and number. Mortality at one year following incident fracture among men with single vs. multiple fractures. Results: Male and female veterans sustained incident fractures with similar observed frequency (10.5% vs 11.5%). The majority of fractures occurred in the lower extremities for both men and women. In men, a complete extent of injury (compared to incomplete) was associated with 41% greater relative risk (RR) of incident fracture (RR 1.41, 95% confidence interval [1.17, 1.70]) among those with tetraplegia, but not paraplegia. Furthermore, many men (33.9%, n = 434) sustained multiple fractures over the course of the study. There were no differences in mortality between men who sustained a single fracture and those who had multiple fractures. Conclusions: The extent of injury may be an important predictor of fracture risk for male veterans with tetraplegia. Once a fracture occurs, male veterans with SCI appear to be at high risk for additional fractures.

Hydroxychloroquine in patients with systemic lupus erythematosus with end-stage renal disease

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.

Urinary Tract Stones and Osteoporosis

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Womens Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis.

Response to Sabour: Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal cord injuries and disorders: methodological issues

Dear Editor, We oppose the points made in Dr. Sabour’s letter “Dualenergy X-ray absorptiometry and fracture prediction in patients with spinal cord injuries and disorders: methodological issues” [1]. The goal of predictive modeling is not to formulate the best possible model to explain a phenomenon under consideration but to construct a useful and statistically defensible model in predicting future outcomes for a given set of observed and/or measured covariates. The model should be able to predict future outcomes under a well-defined statistical form that ideally reflects the features of the study design, effects of interest, and accessible resources that are utilized in the data collection process, among many other things. Yes, the significance of terms that appear in the model may not translate to, or align with, the predictive power of a model as to identifying how outcomes behave in similar observational or controlled settings. The prediction notion and its associated procedures are typically more complicated than what statistical significance arguments suggest. The sky is the limit in terms of the definition of a good predictive model: A formulation that encompasses all the important relationships among variables; that has high statistical power (probability of correctly detecting an effect), low type I error (probability of inventing a non-existing effect or false positives), and low type II error (probability of inadvertently including an unimportant effect or false negatives); that yields small standard errors, narrow confidence, and prediction intervals, etc. One can complicate the statistical model as much as s/he wants to by considering quadratic, cubic, and higherorder polynomials, qualitative factors, interactive effects, and non-linear relationships. Ideally, one may want to have a cross-validation sample for better substantiated inferences. However, none of these good predictive modeling practices hinders the use of the word “predictive.” Even a poorly constructed regression model can be used as a prediction tool. Obviously, this is not desirable and it usually leads to large standard errors, wide intervals, and inaccurate, incoherent, suboptimal, and imprecise conclusions. However, such factors do not nullify or invalidate the predictive nature of the model.

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative: URINARY TRACT STONES AND OSTEOPOROSIS

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Womens Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis.