Association of covert brain infarcts and white matter hyperintensities with risk of hip fracture in older adults: the Cardiovascular Health Study.

Covert brain infarcts and white matter hyperintensities (WMHs), incidental markers of brain microvascular disease commonly seen on brain MRIs in older adults, have been associated with falls and lower bone mineral density. We found covert infarcts and WMHs may also be associated with an increased risk of future hip fracture. INTRODUCTION: To determine whether covert infarcts and white matter hyperintensities (WMHs) are associated with increased risk of incident hip fracture. METHODS: A prospective cohort of 3373 community-dwelling adults aged ≥ 65 years enrolled in the Cardiovascular Health Study with a brain MRI (1992-1993) was analyzed. Covert infarcts were categorized by number of infarcts and largest infarct size. WMH burden was assessed by radiologists and graded qualitatively from 0 (no WMHs) to 9 (extensive). RESULTS: Participants had 465 incident hip fractures during a mean follow-up of 12.8 years. The demographic-adjusted hazard of incident hip fracture was 32% higher among participants with ≥ 1 covert infarct compared to those without infarcts (hazard ratio (HR) 1.32; 95% CI, 1.08-1.62). The hazard of incident hip fracture was similar after further adjustment for medications and medical history (HR = 1.34; 95% CI, 1.08-1.65), but attenuated following additional adjustment for functional status, frailty, and falls (HR = 1.25; 95% CI, 0.99-1.57). Fully adjusted hazard of incident hip fracture per increase in infarct number was 1.10 (95% CI, 0.98-1.23); risk in individuals whose largest infarct was ≥ 20 mm versus 3 to < 20 mm was similar. Compared with WMH grades 0-1, the demographic-adjusted hazard of hip fracture was 1.34 (95% CI, 1.09-1.66) and 1.83 (95% CI, 1.37-2.46), respectively, for WMH grades 2-3 and 4-9. The hazard was similar following adjustment for medications and medical history (grades 2-3: HR = 1.32; 95% CI, 1.05-1.64; grades 4-9: HR = 1.69; 95% CI, 1.23-2.30), but attenuated following additional adjustment for functional status, frailty, and falls (grades 2-3: HR = 1.24; 95% CI, 0.98-1.56; grades 4-9: HR = 1.34; 95% CI, 0.95-1.90). CONCLUSION: Older, community-dwelling adults with covert infarcts or WMHs may be at increased risk of hip fracture.

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.

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.

Reasons for Initiation and Discontinuation of Pharmacological Therapies for Osteoporosis in Veterans with Spinal Cord Injury and Disorders.

INTRODUCTION: Medications for osteoporosis have not been reported to reduce fracture rates in patients with spinal cord injury and disorders (SCI/D), yet these medications are still prescribed. Clinical decision-making underscoring the initiation and discontinuation of osteoporosis medications in SCI/D remains poorly understood. METHODOLOGY: Veterans with a SCI/D with at least one prescription for an osteoporosis medication (bisphosphonate, calcitonin, denosumab, raloxifene, and teriparatide) who received healthcare within Veterans Affairs (VA) from 2005 to 2015 were identified using VA administrative databases. A 10% subsample of Veterans was selected for electronic health record review. RESULTS: Two hundred and sixty-seven Veterans with 330 prescriptions underwent electronic health record review. Bisphosphonates were the most frequently prescribed medication for osteoporosis (n = 223, 67.6%). Of the 187 Veterans with prescriptions for prevention or treatment of osteoporosis, the primary reason for initiation was Dual Energy X-ray Absorptiometry (DXA) scan with osteopenia or osteoporosis (n = 119, 63.6% of Veterans), primarily at the hip (81.0% of DXAs). The majority (79.0%) of DXAs were "screening tests," with SCI/D being the sole reason for the scan. Fractures (n = 51, 27.3%) and fall risk concerns (n = 29, 15.5%) were other major reasons for initiation. On average, oral bisphosphonates were filled for <3 yr, with medication-related side effects (n = 23, 15.8% of bisphosphonates discontinued), predominately gastrointestinal (n = 17, 73.9% of reported side effects), the most common reason for discontinuation. Drug holidays occurred in 14.3% of 35 oral bisphosphonates used for ≥5 yr. No cases of osteonecrosis of the jaw were found. There was one case of an atypical femoral fracture which could not be confirmed. CONCLUSIONS: The decision to initiate pharmacological therapies in SCI/D is primarily based on osteopenia or osteoporosis at the hip by screening DXAs. Gastrointestinal side effects are the major reason for discontinuation of oral bisphosphonates. New therapies for osteoporosis in SCI/D are needed.

Factors influencing providers' decisions on management of bone health in people with spinal cord injury.

STUDY DESIGN: Survey. OBJECTIVES: Managing osteoporosis in persons with chronic spinal cord injury (SCI) is difficult as little evidence exists regarding effective strategies. We examined the effect of key factors on providers' bone health management decisions in persons with SCI. SETTING: USA. METHODS: Providers reviewed blocks of 9 hypothetical cases that varied on four factors: osteoporosis, osteopenia, or normal bone mineral density using dual-energy X-ray absorptiometry (DXA); DXA region of interest (lumbar spine, hip, knee), prior lower extremity fracture; and no or limited ambulation. They indicated how likely they would recommend pharmacological management, what treatment(s) they would recommend, and whether they would request another DXA before treatment. RESULTS: Eighty-two healthcare providers completed the survey. Treatment recommendations for bisphosphonates and Vitamin D/calcium supplements, respectively, were more likely if there was a prior fracture (OR: 2.65, 95%CI: 1.76-3.99, p < 0.0001; OR: 2.96, 95%CI: 1.40-6.26, p = 0.004) and if a DXA scan found osteopenia (OR: 2.23, 95%CI: 1.41-3.54, p = 0.001; OR: 6.56, 95%CI: 2.71-15.85, p < 0.0001) or osteoporosis (OR: 12.08, 95%CI: 7.09-20.57, p < 0.0001; OR: 4.54, 95%CI: 2.08-9.90, p < 0.0001). Another DXA scan was more likely to be requested if there was a prior fracture (OR: 1.75, 95%CI: 1.10-2.78, p = 0.02) but less likely if the person was nonambulatory (OR: 0.41, 95%: 0.19-0.90, p = 0.03). CONCLUSIONS: Prior fracture and DXA findings influenced treatment recommendations for bone health management in SCI. Reliance on lumbar spine scans to determine bone loss and treatment identifies a knowledge gap for which future education is required.

Association of Bisphosphonate Therapy With Incident of Lower Extremity Fractures in Persons With Spinal Cord Injuries or Disorders.

OBJECTIVE: To investigate the association between prescriptions for bisphosphonates; calcium and vitamin D supplements; and receipt of dual-energy x-ray absorptiometry (DXA) screening, and incident fracture risk in men and women with a spinal cord injury (SCI) or disorder (SCID). DESIGN: Propensity-matched case-control analyses. SETTING: United States Veterans Affairs (VA) facilities. PARTICIPANTS: A total of 7989 men and 849 women with an SCID included in VA administrative databases between October 1, 2005 and October 1, 2015 were identified (N=8838). Cases included 267 men and 59 women with a bisphosphonate prescription propensity matched with up to 4 controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incident lower extremity fractures. RESULTS: There was no significant association between prescriptions for bisphosphonates and incident lower extremity fractures in men (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.62-1.77) or women (OR, 1.02; 95% CI, 0.28-3.75). In men, similar null associations were seen among those who were adherent to bisphosphonate therapy (OR, 1.25; 95% CI, 0.73-2.16), were concomitant users of vitamin D and calcium and a bisphosphonate (OR, 1.05; 95% CI, 0.57-1.96), had more than 1 fracture on different dates during the study period (OR, 0.13; 95% CI, 0.02-1.16) and in those who had undergone DXA testing prior to the date of the bisphosphonate prescription and incident fracture (OR, 1.26; 95% CI, 0.69-2.32). CONCLUSIONS: In men with a traumatic SCI and women with a traumatic SCID, bisphosphonate therapies for osteoporosis do not appear to significantly affect fracture risk. Adequately powered randomized controlled trials are needed to definitively demonstrate efficacy of bisphosphonates for fracture prevention in this population. There is a compelling need to identify new medications to prevent fractures in this high-risk population.

The Association of Aromatic Amino Acids with Incident Hip Fracture, aBMD, and Body Composition from the Cardiovascular Health Study.

In 5187 persons from the Cardiovascular Health Study, there was no significant association of dietary intakes of aromatic amino acids (AAA) with areal BMD of the hip or body composition. However, those who had the lowest dietary intakes of AAA were at increased risk for incident hip fractures. Prior studies of the association of protein intake with osteoporosis are conflicting and have not directly examined the relationship of aromatic amino acids (AAA) with fractures, areal bone mineral density (aBMD), and body composition. We sought to determine the relationship of dietary intakes of AAA with osteoporosis parameters in elderly men and women. 5187 men and women aged ≥ 65 years from the Cardiovascular Health Study (CHS) with dietary intakes of AAA (tryptophan, phenylalanine, tyrosine) estimated by food frequency questionnaire (FFQ) were included. We examined the relationship between a one-time estimate of daily dietary AAA intake with risk of incident hip fractures over a median of 13.2 years of fracture follow-up. A subset (n = 1336) who had dual energy X-ray absorptiometry (DXA) performed were included in a cross-sectional analysis of the association of dietary AAA intake with aBMD of the total hip and measurements of body composition. In multivariable models adjusted for demographic and clinical variables, medication use, and diet, higher dietary AAA intake was not significantly associated with incident hip fractures. All hazard ratios (HR) were less than one (tryptophan, HR 0.14, 95% CI 0.01 to 1.89; phenylalanine, HR 0.60, 95% CI 0.23 to 1.55; tyrosine, HR 0.59, 95% CI 0.27 to 1.32), but confidence intervals were wide and included no difference. However, in post hoc analyses, the lowest quartile of intake for each AAA was associated with an increased risk for hip fracture compared to higher quartiles (p ≤ 0.047 for all). Dietary AAA intakes were not significantly associated with total hip aBMD or any measurements of body composition. Overall, there was no significant association of dietary AAA intake with hip fractures, aBMD of the hip, or body composition. However, there may be a subset of elderly individuals with low dietary intakes of AAA who are at increased for hip fractures.

Bone Mineral Density Testing in Spinal Cord Injury: 2019 ISCD Official Position.

Spinal cord injury (SCI) causes rapid osteoporosis that is most severe below the level of injury. More than half of those with motor complete SCI will experience an osteoporotic fracture at some point following their injury, with most fractures occurring at the distal femur and proximal tibia. These fractures have devastating consequences, including delayed union or nonunion, cellulitis, skin breakdown, lower extremity amputation, and premature death. Maintaining skeletal integrity and preventing fractures is imperative following SCI to fully benefit from future advances in paralysis cure research and robotic-exoskeletons, brain computer interfaces and other evolving technologies. Clinical care has been previously limited by the lack of consensus derived guidelines or standards regarding dual-energy X-ray absorptiometry-based diagnosis of osteoporosis, fracture risk prediction, or monitoring response to therapies. The International Society of Clinical Densitometry convened a task force to establish Official Positions for bone density assessment by dual-energy X-ray absorptiometry in individuals with SCI of traumatic or nontraumatic etiology. This task force conducted a series of systematic reviews to guide the development of evidence-based position statements that were reviewed by an expert panel at the 2019 Position Development Conference in Kuala Lumpur, Malaysia. The resulting the International Society of Clinical Densitometry Official Positions are intended to inform clinical care and guide the diagnosis of osteoporosis as well as fracture risk management of osteoporosis following SCI.

Associations of Biomarker-Calibrated Sodium and Potassium Intakes With Cardiovascular Disease Risk Among Postmenopausal Women.

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium.

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.

Bone turnover in long-term survivors of childhood acute lymphoblastic leukemia.

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). PROCEDURE: 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). RESULTS: 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. CONCLUSIONS: 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.

Thiazide use is associated with reduced risk for incident lower extremity fractures in men with spinal cord injury.

OBJECTIVE: To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI). DESIGN: Cohort study from fiscal years 2002 to 2007. SETTING: Medical centers. PARTICIPANTS: Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides. INTERVENTION: Thiazide use versus nonuse. MAIN OUTCOME MEASURE: Incident lower extremity fractures. RESULTS: Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95). CONCLUSIONS: Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures.

Assistive walking device use and knee osteoarthritis: results from the Health, Aging and Body Composition Study (Health ABC Study).

OBJECTIVES: To 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. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: Older adults (N=2639) in the Health, Aging and Body Composition (Health ABC) Study including a subset of 874 patients with prevalent knee pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incident 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. RESULTS: AWD 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. CONCLUSIONS: AWDs 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.

The association of opioid use with incident lower extremity fractures in spinal cord injury.

OBJECTIVE: To determine the association between opioid use and lower extremity fracture risk in men with spinal cord injury (SCI). DESIGN: Retrospective cohort study. SETTING: Veterans Affairs Healthcare System. PARTICIPANTS: 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. OUTCOME MEASURES: Incident lower extremity fractures by use of opioids. RESULTS: 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 (P < 0.0001). CONCLUSIONS: 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.

The Pathophysiology, Identification and Management of Fracture Risk, Sublesional Osteoporosis and Fracture among Adults with Spinal Cord Injury.

BACKGROUND: The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). METHODS: Established best practices and guideline recommendations are articulated in recent international consensus documents from the International Society of Clinical Densitometry, the Paralyzed Veterans of America Consortium for Spinal Cord Medicine and the Orthopedic Trauma Association. RESULTS: This review is a synthesis of the aforementioned consensus documents, which highlight the pathophysiology of lower extremity bone mineral density (BMD) decline after acute SCI. The role and actions treating clinicians should take to screen, diagnose and initiate the appropriate treatment of established low bone mass/osteoporosis of the hip, distal femur or proximal tibia regions associated with moderate or high fracture risk or diagnose and manage a lower extremity fracture among adults with chronic SCI are articulated. Guidance regarding the prescription of dietary calcium, vitamin D supplements, rehabilitation interventions (passive standing, functional electrical stimulation (FES) or neuromuscular electrical stimulation (NMES)) to modify bone mass and/or anti-resorptive drug therapy (Alendronate, Denosumab, or Zoledronic Acid) is provided. In the event of lower extremity fracture, the need for timely orthopedic consultation for fracture diagnosis and interprofessional care following definitive fracture management to prevent health complications (venous thromboembolism, pressure injury, and autonomic dysreflexia) and rehabilitation interventions to return the individual to his/her pre-fracture functional abilities is emphasized. CONCLUSIONS: Interprofessional care teams should use recent consensus publications to drive sustained practice change to mitigate fracture incidence and fracture-related morbidity and mortality among adults with chronic SCI.

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.

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.

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.

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.

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.