Publications

2022
AS Karlamangla, A Shieh, GA Greendale, EW Yu, SM Burnett-Bowie, PM Sluss, D Martin, A Morrison, and JS Finkelstein. 2022. “Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition.” J Bone Miner Res.
Karina N Ruiz-Estevesa, Jimmitti Teysira, Daria Schatoffa, Elaine W Yu, and Sherri-Ann M Burnett-Bowie. 2022. “Disparities in Osteoporosis Care among Postmenopausal Women in the United States.” Maturitas.Abstract
Osteoporosis and fragility fractures result in significant morbidity and mortality and contribute to substantial healthcare costs. Despite being a treatable disease, osteoporosis remains both underdiagnosed and undertreated in the US general population, with significant disparities in care between non-White and White women. These disparities are evident from screening to post-fracture treatment. Non-White women are less likely to be screened for osteoporosis, to be prescribed pharmacotherapy, or to receive treatment post-fracture; furthermore, the mortality rate after fracture is higher in non-White women. Given existing diagnostic and treatment disparities, additional studies and interventions are needed to optimize the bone health of Asian, Black, Hispanic, and Native American women, and to reduce morbidity and mortality from osteoporosis and fragility fractures.
Ignacio Portales-Castillo, David B Mount, Sagar Nigwekar, Elaine W Yu, Helmut Rennke, and Shruti Gupta. 2022. “Zoledronic Acid-Associated Fanconi Syndrome in Patients with Cancer: A Report of 4 Cases.” Am J Kidney Dis.Abstract
Zoledronic acid (ZA) is an anti-resorptive agent typically used for fracture prevention in post-menopausal osteoporosis, malignancy-associated metastatic bone lesions, and as a treatment for hypercalcemia. ZA is excreted almost entirely by the kidney; as a result, a reduction in renal clearance can lead to its accumulation and potential renal toxicity. Although uncommon, AKI from intravenous bisphosphonates has been described, with different patterns including tubulointerstitial nephritis, acute tubular necrosis, as well as focal segmental glomerulosclerosis. Here we present 4 patients with an underlying malignancy who each developed evidence of generalized proximal tubular dysfunction, also known as Fanconi syndrome, approximately 1 week after receiving treatment with ZA. On presentation, all patients had acute kidney injury (AKI), low serum bicarbonate levels, abnormal urinary acidification, hypophosphatemia, hypokalemia, and increased urine amino acid excretion or renal glycosuria. Based on the temporal association between ZA infusion and the development of these electrolyte abnormalities, each case is highly suggestive of ZA-associated Fanconi syndrome. Due to the severity of presentation, all required discontinuation of ZA and ongoing electrolyte repletion. Nephrologists and oncologists should be aware of this complication and consider ZA as a possible trigger of new-onset Fanconi syndrome.
2021
Fjola Johannesdottir, Melissa S Putman, Sherri-Ann M Burnett-Bowie, Joel S Finkelstein, Elaine W Yu, and Mary L Bouxsein. 2021. “Age-related changes in bone density, microarchitecture and strength in postmenopausal Black and White women: SWAN Longitudinal HR-pQCT Study.” J Bone Miner Res.Abstract
Higher fracture risk in White versus Black women is partly explained by lower BMD and worse bone microarchitecture in White women. However, whether rates of decline in bone density, microarchitecture and strength differ between postmenopausal Black and White women is unknown. Further, factors that influence rates of age-related bone microarchitecture deterioration remain ill-defined. Thus, over 6.7 years, longitudinal changes were measured in peripheral volumetric bone mineral density (vBMD), microarchitecture, and strength at the distal radius and tibia using HR-pQCT in postmenopausal Black (n = 80) and White (n = 137) women participating in the Study of Women's Health Across the Nation. It was assessed whether age-related changes in vBMD and microarchitecture were influenced by body weight, body composition, and/or weight change. It was found that at the radius, where White women appeared to have slightly greater rates of loss in total vBMD, cortical bone volume, and porosity than Black women, those differences were attenuated after adjusting for clinical covariates. At the tibia, Black and White women had similar rates of bone loss. Independent of race and other clinical covariates, women with the lowest baseline body weight experienced the greatest decline in total and trabecular vBMD at the radius. Furthermore, women who lost weight over the follow-up period had higher rates of bone loss, particularly at the tibia, compared with those who maintained or gained weight. Higher baseline total body fat mass was also protective of bone loss at both the radius and tibia. In conclusion, these findings indicate that lower fracture risk among postmenopausal Black women is not caused by slower rates of bone deterioration, and highlight the importance for postmenopausal women to avoid lower body weight and excessive weight loss to avert rapid bone loss and subsequent fractures.
Sara J Cromer and Elaine W Yu. 2021. “Challenges and opportunities for osteoporosis care during the COVID-19 pandemic. .” J Clin Endocrinol Metab.Abstract

Purpose: The coronavirus disease 2019 (COVID-19) has both directly and indirectly affected osteoporosis diagnosis and treatment throughout the world.

Methods: This mini-review summarizes the available evidence regarding the effects of COVID-19, its treatment, and the consequences of the pandemic itself on bone health. Additionally, we review evidence and expert recommendations regarding putative effects of osteoporosis medications on COVID-19 outcomes and vaccine efficacy and summarize recommendations for continuation of osteoporosis treatment during the pandemic.

Results: The use of standard screening procedures to assess for osteoporosis and fracture risk declined dramatically early in the pandemic, while rates of fragility fractures were largely unchanged. COVID-19, its treatments, and public health measures to prevent viral spread are each likely to negatively affect bone health. Osteoporosis treatments are not known to increase risk of adverse events from COVID-19, and preclinical data suggest possible beneficial effects of some therapies. Vitamin D deficiency is clearly associated with adverse outcomes from COVID-19, but it remains unclear whether vitamin D supplementation may improve outcomes. Osteoporosis treatment should be continued whenever possible, and recommendations for substituting therapies, if required, are available.

Conclusion: The COVID-19 pandemic has decreased screening and disrupted treatment for osteoporosis. Osteoporosis medications are safe and effective during the pandemic and should be continued whenever possible. Further studies are needed to fully understand the impact of the COVID-19 pandemic on long-term bone health.

Miriam A Bredella, Nazanin Hazhir Karzar, Vibha Singhal, Amita Bose, Abisayo Animashaun, Deborah M Mitchell, Elaine W Yu, and Madhusmita Misra. 2021. “Impact of sleeve gastrectomy on bone outcomes in adolescents vs. adults with obesity. .” Bone.Abstract

Background: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgery (MBS) procedure in adolescents and adults. Only few studies have assessed bone outcomes following SG and it is unknown whether skeletal changes differ by age group. Recent studies have identified marrow adipose tissue (MAT) as a novel biomarker for bone quality with studies in adults showing high MAT in those with visceral adiposity and a reciprocal increase in MAT with bone loss.

Objective: To determine the impact of SG on volumetric BMD (vBMD) and MAT in adolescents and adults with obesity. We hypothesized that SG would lead to a decrease in vBMD and increase in MAT but that these changes would be less pronounced in adolescents compared to adults.

Materials and methods: The study was IRB-approved and HIPAA-compliant. Written informed consent/assent was obtained. We examined 10 adolescents (mean age 17.8 ± 2.5 years, mean BMI 43.5 ± 5.6 kg/m2) and 10 sex, race, and BMI-matched adults (mean age 49.5 ± 13.6 years, mean BMI 43.7 ± 5.9 kg/m2), before and 12 months after SG. At baseline and 12 months, subjects underwent quantitative CT of the lumbar spine (L1-L2) to assess trabecular vBMD, single voxel proton MR spectroscopy at 3 T (PRESS pulse sequence without water suppression) at L1-L2 to quantify MAT, and MRI of the abdomen to assess visceral (VAT) and subcutaneous adipose tissue (SAT).

Results: At baseline, adolescents had lower MAT (p = 0.0002) and higher vBMD (p = 0.050) compared to adults. Adolescents and adults lost 27.9 ± 6.5 vs. 25.0 ± 11.2% of body weight (p < 0.0001 for within group change), while there was no significant difference between groups (p = 0.455). There was a significant reduction in vBMD in adults (-3.9 ± 3.9%, p = 0.005) and a trend for a reduction in adolescents (-3.7 ± 7.5%, p = 0.119), with no significant difference between groups (p = 0.944). Lumbar MAT content increased in both adults and adolescents (p ≤ 0.034), while the difference was not significant between groups (p = 0.281). In adolescents and adults, 12-month percent change in weight and BMI was positively associated with % change in MAT (p ≤ 0.042). 12-month percent change in MAT was positively associated with 12-month % change in SAT in adolescents and 12-month percent change in VAT in adults (p ≤ 0.045).

Conclusion: SG in adolescents and adults with severe obesity is associated with a reduction in lumbar vBMD and an increase in lumbar MAT, although the reduction in adolescents did not reach statistical significance, with no significant differences in these endpoints between groups. Our results suggest detrimental effects of bariatric surgery on bone for patients across the life span.

Ignacio A Portales-Castillo, Cagri Aksu, Sophia Zhao, Ian Strohbehn, Meghan Sise, Elaine W Yu, and Sagar U Nigwekar. 2021. “Prescription Patterns of Osteoporosis Medications in Patients With Advanced CKD: A Retrospective Cohort Study. .” Kidney Med.
Kristin M D'Silva, Sara Jane Cromer, Elaine W Yu, Michael Fischer, and Seoyoung C Kim. 2021. “Risk of Incident Atrial Fibrillation with Zoledronic Acid Versus Denosumab: A Propensity Score-Matched Cohort Study.” J Bone Miner Res, 36, 1, Pp. 52-60.Abstract
Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy-related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. To examine the risk of incident AF among patients receiving ZA compared with denosumab in the first year of treatment, we performed a new-user, active comparator cohort study including privately insured Americans between January 1, 2010, and June 30, 2019. Individuals aged ≥50 years without known arrhythmia or advanced kidney disease who initiated ZA were 1:1 propensity score (PS)-matched to individuals initiating denosumab in separate osteoporosis and malignancy cohorts. The primary outcome was incident diagnosis of AF (≥1 inpatient or ≥2 outpatient diagnostic codes) over 1 year. Secondary outcomes included stroke/transient ischemic attack (TIA) and nonvertebral fracture. In the osteoporosis cohort (n = 16,235 pairs), mean age was 71 years, and 93% were female. There was higher risk of AF with ZA compared with denosumab over 1 year (incidence rate [IR] = 18.6 versus 14.9 per 1000 person-years; hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.04 to 1.50). In the malignancy cohort (n = 7732 pairs), mean age was 70 years, and 66% were female. There was a numerically higher, albeit not statistically significant, risk of AF with ZA compared with denosumab over 1 year (IR = 46.9 versus 39.0 per 1000 person-years; HR = 1.19; 95% CI 1.00 to 1.43; p = 0.06). No difference in stroke/TIA rates occurred. In the malignancy cohort, ZA was less effective than denosumab at preventing nonvertebral fractures (HR = 1.32; 95% CI 1.01 to 1.74). Compared with denosumab, ZA treatment for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk of incident AF in the first year of treatment. 
Sara Jane Cromer, Kristin M D'Silva, Elaine W Yu, Joan Landon, Rishi J Desai, and Seoyoung C Kim. 2021. “Secular Trends in the Pharmacologic Treatment of Osteoporosis and Malignancy-Related Bone Disease from 2009 to 2020. .” J Gen Intern Med.Abstract

Background: New bone-directed therapies, including denosumab, abaloparatide, and romosozumab, emerged during the past decade, and recent trends in use of these therapies are unknown.

Objective: To examine temporal trends in bone-directed therapies.

Design: An open cohort study in a US commercial insurance database, January 2009 to March 2020.

Participants/interventions: All-users of bone-directed therapies age >50 years, users with osteoporosis, users with malignancies, and patients with recent (within 180 days) fractures at key osteoporotic sites.

Main measures: The percentage of each cohort with prescription dispensing or medication administration claims for each bone-directed therapy during each quarter of the study period.

Key results: We analyzed 15.48 million prescription dispensings or medication administration claims from 1.46 million unique individuals (89% women, mean age 69 years). Among all users of bone-directed therapies, alendronate, and zoledronic acid use increased modestly (49 to 63% and 2 to 4%, respectively, during the study period). In contrast, denosumab use increased rapidly after approval in 2010, overtaking use of all other medications except alendronate by 2017 and reaching 16% of users by March 2020. Similar trends were seen in cohorts of osteoporosis, malignancy, and recent fractures. Importantly, use of any bone-directed therapy after fractures was low and declined from 15 to 8%.

Conclusions: Rates of denosumab use outpaced growth of all other bone-directed therapies over the past decade. Treatment rates after osteoporotic fractures were low and declined over time, highlighting major failings in osteoporosis treatment in the US.

Elena Tsourdi, Elaine W Yu, Suzanne Jan M de Beur, and Matthew T Drake. 2021. “Vaccination for COVID-19 and relationship to osteoporosis care: Current evidence and suggested approaches.” J Bone Miner Res.Abstract
The development of coronavirus disease 2019 (COVID-19) vaccines has proceeded at an unprecedented pace, with numerous trials conducted simultaneously across the world as a result of massive technological and financial resource expenditures. With multiple vaccines having now received regulatory approval, public health efforts to promote widespread vaccine dissemination are currently underway. There has been particular emphasis placed on vaccination of older populations, the age group in which COVID-19 infection has been most lethal. However, such widespread vaccination approaches have necessarily raised important questions related to potential interactions with underlying diseases and concomitant treatments among persons to be vaccinated. Osteoporosis is a chronic condition marked by reduced bone strength and an associated increased risk for fracture that generally requires sustained medical intervention(s). Osteoporosis is neither associated with a higher risk of COVID-19 infection nor by more pronounced disease severity following infection, such that individuals with osteoporosis need not be more highly prioritized for COVID-19 vaccination. Osteoporosis therapies do not interfere with the efficacy or side effect profiles of COVID-19 vaccines and should not be stopped or indefinitely delayed because of vaccination. Depending on the specific drug profile within an anti-osteoporosis medication category, minor adjustments to the timing of drug administration may be considered with respect to the patient's COVID-19 vaccination schedule. Herein we provide practical recommendations for the care of patients requiring treatment for osteoporosis in the setting of COVID-19 vaccination.
Yi Liu, Maya M Côté, Michael C Cheney, Katherine G Lindeman, Claire C Rushin, Matthew M Hutter, and Elaine W Yu. 2021. “Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. .” Bone Reports.Abstract

Purpose: Bariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery.

Methods: We performed an open-label pilot study of pre-operative ZOL in postmenopausal women with obesity who were planning RYGB (n = 4). A single dose of zoledronic acid 5 mg was given intravenously prior to RYGB. Serum bone biochemistries including C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at multiple timepoints throughout the 24-week study. BMD was also obtained at the spine and hip by dual-energy x-ray absorptiometry (DXA) and at the trabecular spine by quantitative computed tomography (QCT) at pre-operative baseline and 24 weeks. Results were compared against pre-operative baseline and against changes among RYGB historical controls (n = 10).

Results: At 2 weeks after RYGB, there was a nonsignificant trend for CTX and P1NP levels to be lower than baseline levels in the ZOL group. By 24 weeks after RYGB, however, participants who received ZOL had a significant increase in CTX above pre-operative baseline (+0.228 ± 0.117 ng/dL, p = 0.030) but this CTX rise was less than that observed in the controls (+0.601 ± 0.307 ng/dL, p = 0.042 between groups). Despite ZOL use, participants had significant areal BMD loss at the total hip as compared to pre-operative baseline (-4.2 ± 1.5%, p = 0.012) that was similar in magnitude to total hip BMD loss in the controls (-5.5 ± 3.9%, p = 0.005). There was a suggestion that the ZOL group might be protected against trabecular spine volumetric bone loss as compared to the control group (+4.8 ± 8.0% vs. -5.9 ± 7.0%, p = 0.075 between groups). Serum calcium, 25-hydroxyvitamin D, and parathyroid hormone did not change in either group. No hypocalcemia or serious adverse events were reported after ZOL.

Conclusion: In this proof of concept study, a single dose of ZOL prior to RYGB appeared to transiently mitigate but not fully prevent high bone turnover in the acute postoperative period. At 24 weeks after RYGB, our preliminary data suggest that ZOL was not sufficient to prevent bone loss at the hip, although it may preserve bone density at the trabecular spine. Further prospective, controlled studies are needed to confirm our findings and to identify the best strategies for preventing bone loss in bariatric patients receiving RYGB.

Anna Aulinas, Francisco J Guarda, Elaine W Yu, Melanie S Haines, Elisa Asanza, Lisseth Silva, Nicholas A Tritos, Joseph Verbalis, Karen K Miller, and Elizabeth A Lawson. 2021. “Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men.” Neuroendocrinology, 111, 1-2, Pp. 87-98.Abstract

Introduction: Hypopituitary patients are at risk for bone loss. Hypothalamic-posterior pituitary hormones oxytocin and vasopressin are anabolic and catabolic, respectively, to the skeleton. Patients with hypopituitarism may be at risk for oxytocin deficiency. Whether oxytocin and/or vasopressin contribute to impaired bone homeostasis in hypopituitarism is unknown.

Objectives: To determine the relationship between plasma oxytocin and vasopressin levels and bone characteristics (bone mineral density [BMD] and hip structural analysis [HSA]) in patients who have anterior pituitary deficiencies only (APD group) or with central diabetes insipidus (CDI group).

Methods: This is a cross-sectional study. Subjects included 37 men (17 CDI and 20 APD), aged 20-60 years. Main outcome measures were fasting plasma oxytocin and vasopressin levels, and BMD and HSA using dual X-ray absorptiometry.

Results: Mean BMD and HSA variables did not differ between the CDI and APD groups. Mean BMD Z-scores at most sites were lower in those participants who had fasting oxytocin levels below, rather than above, the median. There were positive associations between fasting oxytocin levels and (1) BMD Z-scores at the spine, femoral neck, total hip, and subtotal body and (2) favorable hip geometry and strength variables at the intertrochanteric region in CDI, but not APD, participants. No associations between vasopressin levels and bone variables were observed in the CDI or ADP groups.

Conclusions: This study provides evidence for a relationship between oxytocin levels and BMD and estimated hip geometry and strength in hypopituitarism with CDI. Future studies will be important to determine whether oxytocin could be used therapeutically to optimize bone health in patients with hypopituitarism.

2020
Kristen M Beavers, Katelyn A Greene, and Elaine W Yu. 2020. “Bone Complications of Bariatric Surgery: Updates on Sleeve Gastrectomy, Fractures, and Interventions.” Eur J Endocrinol.Abstract
Despite well recognized improvements in obesity-related comorbidities, increasing evidence implicates bariatric surgery in the onset of adverse skeletal health outcomes. The purpose of this review is to provide a focused update in three critical areas: (i) emergent data on sleeve gastrectomy and bone loss, (ii) evidence linking bariatric surgery to incident fracture, and (iii) intervention strategies designed to mitigate surgical bone loss. Better understanding of these issues will inform our treatment of skeletal health for patients planning bariatric surgery.
Katherine G Lindeman, Claire C Rushin, Michael C Cheney, Mary L Bouxsein, Matthew M Hutter, and Elaine W Yu. 2020. “Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding.” J Bone Miner Res.Abstract
Roux-en-Y gastric bypass (RYGB) instigates high-turnover bone loss in the initial 5 years after surgery, whereas skeletal changes after adjustable gastric banding (AGB) are less pronounced. Long-term skeletal data are scarce, and the mechanisms of bone loss remain unclear. We sought to examine bone density and microarchitecture in RYGB and AGB patients a decade after surgery and to determine whether prior published reports of bone loss represent an appropriate adaptation to new postsurgical weight. In this cross-sectional study, 25 RYGB and 25 AGB subjects who had bariatric surgery ≥10 years ago were matched 1:1 with nonsurgical controls for age, sex, and current body mass index (BMI). We obtained bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), volumetric BMD and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular morphology by individual trabecular segmentation, and metabolic bone laboratory results. As compared with BMI-matched controls, RYGB subjects had significantly lower hip BMD, and lower total volumetric BMD at the distal radius and tibia. Substantial deficits in cortical and trabecular microarchitecture were observed in the RYGB group compared to controls, with reduced trabecular plate bone volume fraction and estimated failure load at both the radius and tibia, respectively. Bone turnover markers CTX and P1NP were 99% and 77% higher in the RYGB group than controls, respectively, with no differences in serum calcium, 25-hydroxyvitamin D, or parathyroid hormone. In contrast, the AGB group did not differ from their BMI-matched controls in any measured bone density, microarchitecture, or laboratory parameter. Thus, RYGB, but not AGB, is associated with lower than expected hip and peripheral BMD for the new weight setpoint, as well as deleterious changes in bone microarchitecture. These findings suggest that pathophysiologic processes other than mechanical unloading or secondary hyperparathyroidism contribute to bone loss after RYGB, and have important clinical implications for the long-term care of RYGB patients. © 2020 American Society for Bone and Mineral Research.
Joel S Finkelstein, Hang Lee, Sherri-Ann M Burnett-Bowie, Karin Darakananda, Emily C Gentile, David W Goldstein, Sarah H Prizand, Laura M Krivicich, Alexander P Taylor, Kendra E Wulczyn, Benjamin Z Leder, and Elaine W Yu. 2020. “Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men.” J Clin Endocrinol Metab, 105, 8.Abstract
CONTEXT: Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations. OBJECTIVE: To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men. DESIGN, PARTICIPANTS, AND INTERVENTION: 177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls). PRIMARY OUTCOMES: Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire. RESULTS: Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL. CONCLUSION: Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.
Elaine W Yu, Liu Gao, Petr Stastka, Michael C Cheney, Jasmin Mahabamunuge, Mariam Torres Soto, Christopher B Ford, Jessica A Bryant, Matthew R Henn, and Elizabeth L Hohmann. 2020. “Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.” PLoS Med, 17, 3, Pp. e1003051.Abstract
BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.
Elaine W Yu, Elena Tsourdi, Bart L Clarke, Douglas C Bauer, and Matthew T Drake. 2020. “Osteoporosis Management in the Era of COVID-19.” J Bone Miner Res, 35, 6, Pp. 1009-1013.Abstract
Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.
Michael E Lewiecki, John P Bilezikian, Risa Kagan, Deborah Krakow, Michael R McClung, Paul D Miller, Eric T Rush, Christopher R Shuhart, Nelson B Watts, and Elaine W Yu. 2020. “Proceedings of the 2019 Santa Fe Bone Symposium: New Concepts in the Care of Osteoporosis and Rare Bone Diseases.” J Clin Densitom, 23, 1, Pp. 1-20.Abstract
The 20th annual Santa Fe Bone Symposium was held August 9-10, 2019, in Santa Fe, New Mexico, USA. This is an annual meeting devoted to clinical applications of recent advances in skeletal research that impact the care of patients with osteoporosis, metabolic bone diseases, and inherited bone diseases. Participants included practicing and academic physicians, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. The symposium consisted of lectures, case presentations, and panel discussions, with an emphasis on learning through interaction of all attendees. Topics included new approaches in the use of anabolic agents for the treatment osteoporosis, a review of important events in skeletal health over the past year, new and emerging treatments for rare bone diseases, the use of genetic testing for bone diseases in clinical practice, medication-associated causes of osteoporosis, new concepts in the use of estrogen therapy for osteoporosis, new Official Positions of the International Society for Clinical Densitometry, skeletal consequences of bariatric surgery, and update on the progress and potential of Bone Health TeleECHO, a virtual community of practice using videoconferencing technology to link healthcare professionals for advancing the care of osteoporosis worldwide. Sessions on rare bone diseases were developed in collaboration with the Rare Bone Disease Alliance. Symposium premeetings included an FLS workshop by the National Osteoporosis Foundation and others devoted to the use of new therapeutic agents for the care of osteoporosis and related disorders.
2019
Yuichi J Shimada, Koichiro Gibo, Yusuke Tsugawa, Tadahiro Goto, Elaine W Yu, Hiroyasu Iso, David FM Brown, and Kohei Hasegawa. 2019. “Bariatric surgery is associated with lower risk of acute care use for cardiovascular disease in obese adults.” Cardiovasc Res, 115, 4, Pp. 800-806.Abstract
AIMS: Studies have suggested relationships between obesity and cardiovascular disease (CVD) morbidity. However, little is known about whether substantial weight reduction affects the risk of CVD-related acute care use in obese patients with CVD. The objective of this study was to determine whether bariatric surgery is associated with decreased risk of CVD-related acute care use. METHODS AND RESULTS: We performed a self-controlled case series study of obese adults with CVD who underwent bariatric surgery, using population-based emergency department (ED), and inpatient samples in California, Florida, and Nebraska from 2005 to 2011. The primary outcome was ED visit or unplanned hospitalization for CVD. We used conditional logistic regression to compare the risk during sequential 12-month periods, using pre-surgery months 13-24 as the reference period. We identified 11 106 obese adults with CVD who underwent bariatric surgery. During the reference period, 20.6% [95% confidence interval (CI), 19.8-21.3%] of patients had an ED visit or unplanned hospitalization for CVD. The risk did not significantly change in the subsequent 12-month pre-surgery period [adjusted odds ratio (aOR) 0.98; 95% CI, 0.93-1.04; P = 0.42]. By contrast, in the first 12-month period after bariatric surgery, the risk significantly decreased (aOR 0.91; 95% CI, 0.86-0.96; P = 0.002). The risk remained reduced in the subsequent 13-24 months post-bariatric surgery (aOR 0.84; 95% CI, 0.79-0.89; P < 0.001). There was no reduction in the risk in separate obese populations that underwent non-bariatric surgery (i.e. cholecystectomy, hysterectomy). By CVD category, the risk of acute care use for coronary artery disease (CAD), heart failure (HF), and hypertension decreased after bariatric surgery, whereas that of dysrhythmia and venous thromboembolism transiently increased (Bonferroni corrected P < 0.05 for all comparisons). CONCLUSION: Bariatric surgery is associated with a lower risk of overall CVD-related ED visit or unplanned hospitalization. The decline was mainly driven by reduced risk of acute care use for CAD, HF, and hypertension after bariatric surgery.
Melanie Schorr, Anne Drabkin, Micol S Rothman, Erinne Meenaghan, Gillian T Lashen, Margherita Mascolo, Ashlie Watters, Tara M Holmes, Kate Santoso, Elaine W Yu, Madhusmita Misra, Kamryn T Eddy, Anne Klibanski, Philip Mehler, and Karen K Miller. 2019. “Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant/restrictive food intake disorder.” Clin Endocrinol (Oxf), 90, 6, Pp. 789-797.Abstract
OBJECTIVE: Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders. DESIGN: Cross-sectional: two centres. PATIENTS: A total of 103 men, 18-63 years: AN (n = 26), ARFID (n = 11), ATYP (n = 18), healthy controls (HC) (n = 48). MEASUREMENTS: Body composition, BMD and estimated hip strength (section modulus and buckling ratio) by DXA (Hologic). Serum 25OH vitamin D was quantified, as was daily calcium intake in a subset of subjects. RESULTS: Mean BMI was lowest in AN and ARFID, higher in ATYP and highest in HC (AN 14.7 ± 1.8, ARFID 15.3 ± 1.5, ATYP 20.6 ± 2.0, HC 23.7 ± 3.3 kg/m ) (P < 0.0005). Mean BMD Z-scores at spine and hip were lower in AN and ARFID, but not ATYP, than HC (postero-anterior (PA) spine AN -2.05 ± 1.58, ARFID -1.33 ± 1.21, ATYP -0.59 ± 1.77, HC -0.12 ± 1.17) (P < 0.05). 65% AN, 18% ARFID, 33% ATYP and 6% HC had BMD Z-scores <-2 at ≥1 site (AN and ATYP vs HC, P < 0.01). Mean section modulus Z-scores were lower in AN than HC (P < 0.01). Lower BMI, muscle mass and vitamin D levels (R = 0.33-0.64), as well as longer disease duration (R = -0.51 to -0.58), were associated with lower BMD (P < 0.05). CONCLUSIONS: Men with AN, ARFID and ATYP are at risk for low BMD. Men with these eating disorders who are low weight, or who have low muscle mass, long illness duration and/or vitamin D deficiency, may be at particularly high risk.

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