Association of serum levels of phenylalanine and tyrosine with hip fractures and frailty in older adults: The cardiovascular health study.

This study examined if the amino acids phenylalanine or tyrosine contribute to risk of hip fracture or frailty in older adults. We determined that neither phenylalanine nor tyrosine are important predictors of hip fracture or frailty. We suggest advice on protein intake for skeletal health consider specific amino acid composition. PURPOSE: Protein is essential for skeletal health, but the specific amino acid compositions of protein may have differential associations with fracture risk. The aim of this study was to determine the association of serum levels of the aromatic amino acids phenylalanine and tyrosine with risk for incident hip fractures over twelve years of follow-up and cross sectional associations with frailty. METHODS: We included 131 older men and women from the Cardiovascular Health Study (CHS) who sustained a hip fracture over twelve years of follow-up and 131 men and women without an incident hip fracture over this same period of time. 42% of this cohort were men and 95% were Caucasian. Weighted multivariable Cox hazards molecules were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher serum level of phenylalanine or tyrosine. Relative risk regression was used to determine the cross-sectional association of these amino acids with Freid's frailty index. RESULTS: Neither serum levels of phenylalanine (HR 0.85 (95% CI 0.62-1.16) or tyrosine (HR 0.82 (95% CI 0.62-1.1) were significantly associated with incident hip fractures or cross sectionally with frailty (frail compared with prefrail/not frail) (HR 0.92 (95% CI 0.48-1.76) and HR (0.86 (95% CI 0.46-1.61) respectively. CONCLUSION: Phenylalanine and tyrosine are not significant contributors to hip fractures or frailty in older men and women.

The Association of Tryptophan and Its Metabolites With Incident Hip Fractures, Mortality, and Prevalent Frailty in Older Adults: The Cardiovascular Health Study.

Amino acids are the building blocks of proteins, and sufficient protein intake is important for skeletal health. We utilized stored serum from the Cardiovascular Health Study in 1992-1993 to examine the relationship between levels of the essential amino acid tryptophan (trp) and its oxidized and nonoxidized metabolites to risk for incident hip fractures and mortality over 12 years of follow-up. We included 131 persons who sustained a hip fracture during this time period and 131 without a hip fracture over these same 12 years of follow-up; 58% female and 95% White. Weighted multivariable Cox hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher trp or its metabolites exposure. Relative risk regression was used to evaluate the cross-sectional association of trp and its metabolites with frailty. Higher serum levels of trp were significantly associated with lower risk of incident hip fractures (HR = 0.75 per SD of trp (95% CI 0.57-0.99) but were not significantly associated with mortality or frailty status by Freid's frailty index. There were no statistically significant associations between any of the oxidized or nonoxidized products of trp with incident hip fractures (p ≥ 0.64), mortality (p ≥ 0.20), or cross-sectional frailty status (p ≥ 0.13) after multiple testing adjustment. Randomized clinical trials examining whether increasing trp intake is beneficial for osteoporosis are needed. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Association of Immune Cell Subsets with Incident Hip Fracture: The Cardiovascular Health Study.

In this study, we aimed to evaluate the association of innate and adaptive immune cell subsets in peripheral blood mononuclear cells (PBMCs) with hip fracture. To conduct this study, we used data from the Cardiovascular Health Study (CHS), a U.S. multicenter observational cohort of community-dwelling men and women aged ≥ 65 years. Twenty-five immune cell phenotypes were measured by flow cytometry from cryopreserved PBMCs of CHS participants collected in 1998-1999. The natural killer (NK), γδ T, T helper 17 (Th17), and differentiated/senescent CD4+CD28- T cell subsets were pre-specified as primary subsets of interest. Hip fracture incidence was assessed prospectively by review of hospitalization records. Multivariable Cox hazard models evaluated associations of immune cell phenotypes with incident hip fracture in sex-stratified and combined analyses. Among 1928 persons, 259 hip fractures occurred over a median 9.7 years of follow-up. In women, NK cells were inversely associated with hip fracture [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.60-0.99 per one standard deviation higher value] and Th17 cells were positively associated with hip fracture [HR 1.18, 95% CI 1.01-1.39]. In men, γδ T cells were inversely associated with hip fracture [HR 0.60, 95% CI 0.37-0.98]. None of the measured immune cell phenotypes were significantly associated with hip fracture incidence in combined analyses. In this large prospective cohort of older adults, potentially important sex differences in the associations of immune cell phenotypes and hip fracture were identified. However, immune cell phenotypes had no association with hip fracture in analyses combining men and women.

Pulmonary-Renal Syndrome from Levamisole-Adulterated Cocaine-Induced Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review.

Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22-58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment.

Plasma Levels of Branched Chain Amino Acids, Incident Hip Fractures, and Bone Mineral Density of the Hip and Spine.

OBJECTIVE: Branched chain amino acids (BCAA) are building blocks for protein, an essential component of bone. However, the association of plasma levels of BCAA with fractures in populations outside of Hong Kong or with hip fractures in particular is not known. The purpose of these analyses was to determine the relationship of BCAA including valine, leucine, and isoleucine and total BCAA (SD of the sum of Z-scores for each BCAA) with incident hip fractures and bone mineral density (BMD) of the hip and lumbar spine in older African American and Caucasian men and women in the Cardiovascular Health Study. DESIGN: Longitudinal analyses of association of plasma levels of BCAA with incident hip fractures and cross-sectional BMD of the hip and lumbar spine from the Cardiovascular Health Study. SETTING: Community. PARTICIPANTS: A total of 1850 men (38% of cohort) and women; mean age 73 years. MAIN OUTCOME MEASURES: Incident hip fractures and cross-sectional BMD of the total hip, femoral neck, and lumbar spine. RESULTS: In fully adjusted models, over 12 years of follow-up, we observed no significant association between incident hip fracture and plasma values of valine, leucine, isoleucine, or total BCAA per 1 SD higher of each BCAA. Plasma values of leucine but not valine, isoleucine, or total BCAA, were positively and significantly associated with BMD of the total hip (P = .03) and femoral neck (P = .02), but not the lumbar spine (P = .07). CONCLUSIONS: Plasma levels of the BCAA leucine may be associated with higher BMD in older men and women. However, given the lack of significant association with hip fracture risk, further information is needed to determine whether BCAAs would be novel targets for osteoporosis therapies.

Mortality Following Hip Fracture in Older Adults With and Without Coronary Heart Disease.

BACKGROUND: Comorbidities like coronary heart disease are common among older people who sustain an osteoporotic hip fracture. However, their impact on short- and long-term mortality post-hip fracture is not well quantified. METHODS: We examined 4092 and 1173 older adults without and with prevalent coronary heart disease, respectively. Post-hip fracture mortality rates were computed with Poisson models and hazard ratios with Cox regression. For perspective, we compared mortality rates among participants with prevalent coronary heart disease who had either a hip fracture or incident heart failure (but no hip fracture). RESULTS: Among participants without prevalent coronary heart disease, the mortality rate post-hip fracture was 21.83 per 100 participant years, including 49.27 per 100 participant years in the first 6 months following hip fracture. Among participants with prevalent coronary heart disease, the corresponding mortality rates were 32.52 and 79.44 per 100 participant years, respectively. Participants with prevalent coronary heart disease and incident heart failure (but no hip fracture) had corresponding post-incident heart failure mortality rates per 100 participant years of 25.62 overall and 46.4 in the first 6 months. In all 3 groups, the hazard ratio for mortality was similarly elevated: 5- to 7-fold at 6 months and 1.7- to 2.5-fold beyond 5 years. CONCLUSION: As a case study in the absolute effects of a comorbidity on post-hip fracture mortality, hip fracture in a person with coronary heart disease carries an exceedingly high mortality rate, even higher than that following incident heart failure in individuals with coronary heart disease.

The associations of markers of endothelial dysfunction with hip fracture risk.

Endothelial dysfunction underlies the development of atherosclerotic vascular disease, which in turn is associated with osteoporotic fractures. Here, we examined the association of two markers of endothelial dysfunction with incident hip fracture risk in older adults but found no statistically significant associations between them. PURPOSE/INTRODUCTION: Endothelial dysfunction underlies the development of atherosclerotic vascular disease. Vascular disease, in turn, is associated with the risk of osteoporotic fractures, such as hip fractures. Here, we examine whether two measures of endothelial dysfunction are related to hip fracture risk. METHODS: Participants for this study were 2792 individuals (mean age 78.6 years) who had flow-mediated dilation (FMD) measured after ischemia in the forearm and 2255 adults (mean age 73.3 years) with measured soluble intercellular adhesion molecule (siCAM) levels, a constitutive endothelial cell membrane protein associated with the initiation of atherosclerosis. Mean follow-up was 9.7 and 11.7 years, respectively. There were 375 and 265 incident hip fractures, respectively, in each group. RESULTS: In Cox proportional hazards models, there was no significant association between FMD response and incident hip fracture (HR per 1% higher FMD was 0.98 [0.93, 1.04]; p = 0.44). In exploratory analyses, when data were examined dichotomously, participants in the lowest 80% of FMD (≤ 4.5%) had an adjusted 1.29 (0.98, 1.68; p = 0.067) higher hazard of hip fracture compared to participants in the upper 20% of FMD change. There were no significant associations between siCAM and incident hip fracture whether examined as a continuous or dichotomized variable. CONCLUSIONS: Among older adults, two measures of endothelial dysfunction were not significantly associated with hip fracture risk. There was a trend for higher fracture risk with lower FMD.

Initial presentation of granulomatosis with polyangiitis as urethral mass mimicking urethral cancer: A case report.

Granulomatosis with polyangiitis (GPA) is a type of vasculitis in which granulomas deposit in small and medium-size vessels causing inflammation. It frequently affects the respiratory tract, both upper and lower tracts. Glomerulonephritis commonly occurs as well, and other systems can be affected such as the integumentary system and peripheral nervous system. Rarely, urogenital signs and symptoms are present. This report describes a case of a 19-year-old woman who presented with lower urinary tract symptoms and a urethral mass and was subsequently diagnosed with GPA. She responded well to treatment with corticosteroids, rituximab, and avacopan. This case highlights the importance of considering alternative diagnoses when a young woman presents with refractory urinary symptoms. It also highlights fertility issues relative to treatment of GPA that are of interest to the practicing obstetrician/gynecologist.

Predictors of lower extremity fracture-related amputation in persons with traumatic spinal cord injury: a case-control study.

STUDY DESIGN: This is a retrospective case-control study. OBJECTIVES: To identify predictors of lower extremity (LE) long bone fracture-related amputation in persons with traumatic spinal cord injury (tSCI). SETTING: US Veterans Health Administration facilities (2005-2015). METHODS: Fracture-amputation sets in Veterans with tSCI were considered for inclusion if medical coding indicated a LE amputation within 365 days following an incident LE fracture. The authors adjudicated each fracture-amputation set by electronic health record review. Controls with incident LE fracture and no subsequent amputation were matched 1:1 with fracture-amputation sets on site and date of fracture (±30 days). Multivariable conditional logistic regression determined odds ratios (OR) and 95% confidence intervals (CI) for potential predictors (motor-complete injury; diabetes mellitus (DM); peripheral vascular disease (PVD); smoking; primary (within 30 days) nonsurgical fracture management; pressure injury and/or infection), controlling for age and race. RESULTS: Forty fracture-amputation sets from 37 Veterans with LE amputations and 40 unique controls were identified. DM (OR = 26; 95% CI, 1.7-382), PVD (OR = 30; 95% CI, 2.5-371), and primary nonsurgical management (OR = 40; 95% CI, 1.5-1,116) were independent predictors of LE fracture-related amputation. CONCLUSIONS: Early and aggressive strategies to prevent DM and PVD in tSCI are needed, as these comorbidities are associated with increased odds of LE fracture-related amputation. Nonsurgical fracture management increased the odds of LE amputation by at least 50%. Further large, prospective studies of fracture management in tSCI are needed to confirm our findings. Physicians and patients should consider the potential increased risk of amputation associated with non-operative management of LE fractures in shared decision making.

Sex and Racial Differences in Systemic Lupus Erythematosus Among US Adults in the All of Us Research Program.

OBJECTIVE: Men with systemic lupus erythematosus (SLE) are an understudied population. The present study characterized differences between men and women with SLE. METHODS: We examined cross-sectionally participants with SLE in the All of Us Research Program, a US cohort with a participant survey at enrollment (May 2018 to June 2022) and linked electronic health record (EHR) data. We described and compared characteristics of men and women with SLE encompassing disease manifestations and prescribed medications from EHR data and socioeconomic factors, including health literacy and health care access and utilization, from surveys. We reported racial variations stratified by sex. RESULTS: Of 1,462 participants with SLE, 126 (9%) were male. Men reported lower educational attainment and less fatigue than women. Myocardial infarction was significantly more common in men. Men had significantly less confidence in completing medical forms than women and exhibited a trend toward requiring more help in reading health-related materials. Barriers to health care access and utilization were common in both men and women (40% versus 47%, respectively, reporting some reason for delay in care; P = 0.35). Women of race other than Black or African American or White more often reported delaying care due to cultural differences between patient and provider. CONCLUSION: Our study demonstrated major clinical and health literacy differences in men and women with SLE. Socioeconomic factors were significant barriers to health care in both sexes. Our study suggests men have disproportionately poorer health literacy, which may exacerbate preexisting disparities. Further large prospective studies, focusing on recruiting men, are needed to better characterize racial differences in men with SLE.

"Pathological" fractures in spinal cord injuries and disorders: Insight into International classification of diseases, ninth revision coding.

OBJECTIVE: Analyses of osteoporosis-related fractures in persons with Spinal Cord Injury or Disorder (SCID) using administrative data often exclude pathological fractures (International Classification of Diseases, Ninth Revision (ICD-9) codes 733.1x). We examined how often lower extremity "pathological" fractures were secondary to osteoporosis. DESIGN: Retrospective case-control study, fiscal years 2005-2015. SETTING: Veterans Health Administration. PARTICIPANTS: Veterans with SCID and an ICD-9 code for lower extremity fracture. OUTCOME MEASURES: Clinical and SCID-related characteristics were compared in pathological and non-pathological fractures. A subset of Veterans with lower extremity fracture had data on fracture etiology from prior electronic health record (eHR) review. Of these, all with eHR-confirmed pathological fractures were considered cases. For each case, four unmatched controls with non-pathological fractures from this subset were randomly selected. Fracture etiology was compared between subsample cases and controls. We sought expert opinion from specialists who care for these fractures to understand their perspectives on what constitutes a pathological fracture and narrate our findings. RESULTS: 6,397 Veterans sustained 16,279 lower extremity fractures, including 314 (1.93%) pathological fractures in 264 Veterans. Ten of 13 (76.9%) cases of pathological fracture (76.9%) and 82.4% of non-pathological fractures were secondary to osteoporosis. Of the 19 experts surveyed, only two coded osteoporotic fractures as pathological. CONCLUSION: Most pathological lower extremity fractures by ICD-9 codes in SCID are secondary to osteoporosis. Pathological fractures can be considered for inclusion in epidemiologic studies of osteoporosis in SCID when the risk-benefit profile for the study favors capturing all osteoporotic fractures at the expense of some misclassification.

The Association of Lipids and Lipoproteins with Hip Fracture Risk: The Cardiovascular Health Study.

BACKGROUND: It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels and lipoprotein levels and sizes was examined. METHODS: We followed 5832 participants aged ≥65 years from the Cardiovascular Health Study for hip fracture for a mean of 13.5 (SD 5.7) years. Standard enzymatic methods were used to determine lipid levels (ie, high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], and triglycerides). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein fractions (ie, very-low-density lipoprotein-particle [VLDL-P], low-density lipoprotein-particle [LDL-P], high-density lipoprotein-particle [HDL-P]) in a subset of 1849 participants. RESULTS: We documented 755 incident hip fractures among women (1.19 fractures per 100 participant years [95% confidence interval, 1.04, 1.35]) and 197 among men (0.67 fractures per 100 participant years [95% CI, 0.41, 1.10]) over an average follow-up. HDL-c and LDL-c levels had statistically significant nonlinear U-shaped relationships with hip fracture risk (HDL-c, P = .009; LDL-c, P = .02). Triglyceride levels were not significantly associated with hip fracture risk. In fully adjusted conjoint models, higher VLDL-P concentration (hazard ratio [HR] per 1 standard deviation [SD] increment 1.47 [1.13, 1.91] and size [HR per 1 SD increment 1.24 [1.05, 1.46]) and higher high-density lipoprotein particle size (HR per 1 SD increment 1.81 [1.25, 2.62]) were all associated with higher hip fracture risk. CONCLUSIONS: Lipids and lipoproteins are associated with hip fracture risk in older adults. The associations are complex. Mechanistic studies are needed to understand these findings.

Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study.

CONTEXT: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain. OBJECTIVE: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. DESIGN AND SETTING: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study. PARTICIPANTS: 5019 U.S. adults aged ≥65 years. EXPOSURE: Plasma TMAO. MAIN OUTCOME MEASURES: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400). RESULTS: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm2*100 [-0.34,1.17] per TMAO doubling; men: 0.19[-1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P < 0.01). Higher TMAO was significantly associated with risk of hip fracture in adults with overweight or obesity (BMI ≥ 25) (HR [95% CI]:1.17[1.05,1.31]), but not normal or underweight. CONCLUSIONS: Among older US men and women, TMAO was not significantly associated with risk of hip fracture or BMD overall. Exploratory analyses suggested a significant association between higher TMAO and hip fracture when BMI was elevated, which merits further study.

Risk Factors and Consequences of Lower Extremity Fracture Nonunions in Veterans With Spinal Cord Injury.

We used Veterans Health Administration (VHA) national administrative data files to identify a cohort (fiscal years 2005-2014) of veterans with spinal cord injuries and disorders (SCID) to determine risk factors for and consequences of lower extremity fracture nonunions. Odds ratios (OR) for fracture nonunion were computed using multivariable-adjusted logistic regression models. We identified three risk factors for nonunion: (i) older age (OR = 2.29; 95% confidence interval [CI] 1.21-4.33), (ii) longer duration of SCID (OR = 1.02; 95% CI 1.00-1.04), and (iii) fracture site (distal femur), with OR (comparison distal femur) including distal tibia/fibula (OR = 0.14; 95% CI 0.09-0.24), proximal tibia/fibula (OR = 0.19; 95% CI 0.09-0.38), proximal femur (OR = 0.10; 95% CI 0.04-0.21), and hip (OR = 0.13; 95% CI 0.07-0.26). Nonunions resulted in multiple complications, with upwards of 1/3 developing a pressure injury, 13% osteomyelitis, and almost 25% requiring a subsequent amputation. Our data have identified a high-risk population for fracture nonunion of older veterans with a long duration of SCID who sustain a distal femur fracture. In view of the serious complications of these nonunions, targeted interventions in these high-risk individuals who have any signs of delayed union should be considered. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Lower extremity fracture prevention and management in persons with spinal cord injuries and disorders: The patient perspective.

CONTEXT/OBJECTIVE: To describe patient experiences with fracture prevention and management among persons with spinal cord injuries/disorders (SCI/D). DESIGN: Qualitative data collected via semi-structured telephone interviews. SETTING: Veterans Health Administration (VA) SCI/D System of Care. PARTICIPANTS: Veterans with SCI/D (n = 32) who had experienced at least one lower-extremity fracture in the prior 18 months. INTERVENTIONS: N/A. OUTCOME MEASURES: Interview questions addressed patients': pre-fracture knowledge of osteoporosis and bone health, diagnosis and management of osteoporosis, history and experiences with fracture treatment, and post-fracture care and experiences. RESULTS: Participants expressed concerns about bone health and fractures in particular, which for some, limited activities and participation. Participants recalled receiving little information from providers about bone health or osteoporosis and described little knowledge about osteoporosis prevention prior to their fracture. Few participants reported medication management for osteoporosis, however many reported receiving radiographs/scans to confirm a fracture and most reported being managed non-operatively. Some reported preference for surgical treatment and believed their outcomes would have been better had their fracture been managed differently. Many reported not feeling fully included in treatment decision-making. Some described decreased function, independence and/or participation post-fracture. CONCLUSION(S): Our results indicate that persons with SCI/D report lacking substantive knowledge about bone health and/or fracture prevention, and following fracture, feel unable and/or hesitant to resume pre-fracture participation. In addition, our findings indicate that individuals with SCI/D may not feel as engaged as they would like to be in establishing fracture treatment plans. As such, persons with SCI/D may benefit from ongoing discussions with providers about risks and benefits of fracture treatment options and consideration of subsequent function and participation, to ensure patients preferences are considered.

Cardiovascular autonomic nervous system function and hip fracture risk: the Cardiovascular Health Study.

Among 1299 older adults with 24-h Holter monitoring data at baseline, followed for approximately 15 years, 190 incident hip fractures occurred. Increased heart rate variability was independently associated with reduced risk of hip fracture among female participants. PURPOSE: Autonomic nervous system function modulates bone remodeling in rodent osteoporosis models. We tested whether cardiovascular autonomic function is associated with hip fracture risk in humans. METHODS: Participants were 1299 subjects from the Cardiovascular Health Study (mean age 72.8 years). Eight heart rate variability (HRV) measures (time and frequency domains, detrended fluctuation analysis variables, and heart rate turbulence) were derived from 24-h Holter monitor scans in sinus rhythm. Median follow-up for incident hip fracture was 14.7 years [IQR 9.1, 20.2]. Cox proportional hazards models were used to calculate hazard ratios (95% confidence intervals, CI). RESULTS: There were 144 hip fractures among 714 women (1.31 [1.06, 1.61] per 100-person years) and 46 among 585 men (0.62 [0.43, 0.90] per 100 person-years). From among HRV variables examined, a one standard deviation (SD) higher variation between normal heart beats over 24 h (the SD of NN intervals [SDNN]) was associated with a multivariable-adjusted lower hip fracture risk (HR [Formula: see text] 0.80; 95% CI 0.65-0.99; p = 0.04) in women. The adjusted association between very low frequency power, and hip fracture was borderline statistically significant in women (HR [Formula: see text] 0.82; 95% CI, 0.66-1.00; p = 0.06). When the 8 HRV variables were considered conjointly and adjusted for each other's association with hip fracture risk, a 1 SD higher SDNN value was significantly associated with reduced hip fracture risk in women (HR 0.74; 95% CI, 0.50-0.99; p = 0.05). No HRV variables were associated with hip fracture in men. CONCLUSIONS: In older women, increased heart rate variation is associated with hip fracture risk.

The Association of Methotrexate, Sulfasalazine, and Hydroxychloroquine Use With Fracture in Postmenopausal Women With Rheumatoid Arthritis: Findings From the Women's Health Initiative.

This study was conducted to evaluate the extent to which disease-modifying antirheumatic medications (DMARDs) used as part of a triple therapy for the treatment of rheumatoid arthritis (RA) including methotrexate, sulfasalazine, and hydroxychloroquine are associated with fractures in postmenopausal women with RA. Incident fractures following use of methotrexate, sulfasalazine, and/or hydroxychloroquine in postmenopausal women with RA in the Women's Health Initiative were estimated by Cox proportional hazards using hazard ratios (HRs) and 95% CIs after consideration of potential confounders. There were 1201 women with RA enrolled in the Women's Health Initiative included in these analyses, of which 74% were white, 17% were black, and 9% were of other or unknown race/ethnicity. Of the women with RA, 421 (35%) had not used methotrexate, sulfasalazine, or hydroxychloroquine, whereas 519 (43%) women had used methotrexate, 83 (7%) sulfasalazine, and 363 (30%) hydroxychloroquine alone or in combination at some time during study follow-up. Over a median length of 6.46 years of follow-up, in multivariable adjusted models, no statistically significant association was found between methotrexate (HR, 1.1; 95% CI, 0.8-1.6), sulfasalazine (HR, 0.6; 95% CI, 0.2-1.5), or hydroxychloroquine (HR, 1.0; 95% CI, 0.7-1.5) use and incident fractures or between combination therapy with methotrexate and sulfasalazine or methotrexate and hydroxychloroquine use (HR, 0.9; 95% CI, 0.5-1.6) and incident fractures. In conclusion, postmenopausal women with RA receiving any component of triple therapy should not be expected to have any substantial reduction in fracture risk from use of these DMARDs. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fractures in patients with rheumatoid arthritis and end-stage renal disease.

Having rheumatoid arthritis (RA) or end-stage renal disease (ESRD) can lead to fractures. RA independently increases the risk of hip or other femur fracture in dialysis patients. Use of corticosteroids is a potentially modifiable risk factor for fractures among persons with RA and ESRD on dialysis. PURPOSE: Rheumatoid arthritis (RA) and end-stage renal disease (ESRD) both independently increase fracture risk; however, how RA and ESRD interplay to affect fracture risk is unknown. We aim to determine the association of RA with fracture in ESRD and identify risk factors for fracture in patients with RA and ESRD. METHODS: A retrospective cohort study was conducted using the United States Renal Data System (USRDS) to identify ESRD adults with and without a history of RA who initiated dialysis in 2005-2008. International Classification of Diseases, 9th Revision (ICD-9) codes were used to identify fractures following start of dialysis. Risk for incident fracture was compared between those with and without RA. Potential risk factors for fracture among persons with RA and ESRD were analyzed. RESULTS: There were 754 persons with ESRD and RA, of whom 126 (17%) had any incident fracture. In multivariable adjusted final models, among ESRD patients, RA was an independent risk factor for hip/femur fracture (RR 1.28, 95% CI 1.01-1.64). Among persons with RA and ESRD, in final models, only corticosteroid use was a significant risk factor for both any incident (RR 2.00, 95% CI 1.40-2.87) and hip/femur (RR 1.97, 95% CI 1.24-3.11) fracture. Those with higher body mass index had a lower relative risk of hip/femur fracture (RR 0.95, 95% CI 0.91-0.99). CONCLUSION: Among ESRD patients, those with RA have a 28% increased risk for hip or other femur fracture. Use of corticosteroids is a potentially modifiable risk factor for fractures among persons with RA and ESRD.