@article{pmid38590141,

title = {The American Society for Bone and Mineral Research Task Force on clinical algorithms for fracture risk report},

author = {Sherri-Ann M Burnett-Bowie and Nicole C Wright and Elaine W Yu and Lisa Langsetmo and Gabby M H Yearwood and Carolyn J Crandall and William D Leslie and Jane A Cauley},

doi = {10.1093/jbmr/zjae048},

issn = {1523-4681},

year  = {2024},

date = {2024-04-01},

journal = {J Bone Miner Res},

abstract = {Using race and ethnicity in clinical algorithms potentially contributes to health inequities. The American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee convened the ASBMR Task Force on Clinical Algorithms for Fracture Risk to determine the impact of race and ethnicity adjustment in the US Fracture Risk Assessment Tool (US-FRAX). The Task Force engaged the University of Minnesota Evidence-based Practice Core to conduct a systematic review investigating the performance of US-FRAX for predicting incident fractures over 10 years in Asian, Black, Hispanic, and White individuals. Six studies from the Women's Health Initiative (WHI) and Study of Osteoporotic Fractures (SOF) were eligible; cohorts only included women and were predominantly White (WHI > 80% and SOF > 99%), data were not consistently stratified by race and ethnicity, and when stratified there were far fewer fractures in Black and Hispanic women vs White women rendering area under the curve (AUC) estimates less stable. In the younger WHI cohort (n = 64 739), US-FRAX without bone mineral density (BMD) had limited discrimination for major osteoporotic fracture (MOF) (AUC 0.53 (Black), 0.57 (Hispanic), and 0.57 (White)); somewhat better discrimination for hip fracture in White women only (AUC 0.54 (Black), 0.53 (Hispanic), and 0.66 (White)). In a subset of the older WHI cohort (n = 23 918), US-FRAX without BMD overestimated MOF. The Task Force concluded that there is little justification for estimating fracture risk while incorporating race and ethnicity adjustments and recommends that fracture prediction models not include race or ethnicity adjustment but instead be population-based and reflective of US demographics, and inclusive of key clinical, behavioral, and social determinants (where applicable). Research cohorts should be representative vis-à-vis race, ethnicity, gender, and age. There should be standardized collection of race and ethnicity; collection of social determinants of health to investigate impact on fracture risk; and measurement of fracture rates and BMD in cohorts inclusive of those historically underrepresented in osteoporosis research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38505529,

title = {Use of noninvasive imaging to identify causes of skeletal fragility in adults with diabetes: a review},

author = {Shannon R Emerzian and Fjola Johannesdottir and Elaine W Yu and Mary L Bouxsein},

doi = {10.1093/jbmrpl/ziae003},

issn = {2473-4039},

year  = {2024},

date = {2024-02-01},

journal = {JBMR Plus},

volume = {8},

number = {2},

pages = {ziae003},

abstract = {Diabetes, a disease marked by consistent high blood glucose levels, is associated with various complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Notably, skeletal fragility has emerged as a significant complication in both type 1 (T1D) and type 2 (T2D) diabetic patients. This review examines noninvasive imaging studies that evaluate skeletal outcomes in adults with T1D and T2D, emphasizing distinct skeletal phenotypes linked with each condition and pinpointing gaps in understanding bone health in diabetes. Although traditional DXA-BMD does not fully capture the increased fracture risk in diabetes, recent techniques such as quantitative computed tomography, peripheral quantitative computed tomography, high-resolution quantitative computed tomography, and MRI provide insights into 3D bone density, microstructure, and strength. Notably, existing studies present heterogeneous results possibly due to variations in design, outcome measures, and potential misclassification between T1D and T2D. Thus, the true nature of diabetic skeletal fragility is yet to be fully understood. As T1D and T2D are diverse conditions with heterogeneous subtypes, future research should delve deeper into skeletal fragility by diabetic phenotypes and focus on longitudinal studies in larger, diverse cohorts to elucidate the complex influence of T1D and T2D on bone health and fracture outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37865478,

title = {Racial and Ethnic Disparities in Metabolic Bone Disease},

author = {Lauren Y Maldonado and Linette Bosques and Sara J Cromer and Sharl S Azar and Elaine W Yu and Sherri-Ann M Burnett-Bowie},

doi = {10.1016/j.ecl.2023.05.004},

issn = {1558-4410},

year  = {2023},

date = {2023-12-01},

journal = {Endocrinol Metab Clin North Am},

volume = {52},

number = {4},

pages = {629--641},

abstract = {Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic bone disease, osteoporosis remains underscreened and undertreated among Black women. Skeletal-related events in metastatic cancer include bone pain, pathologic fractures, and spinal cord compression. Disparities in screening for and treating skeletal-related events disproportionately affect Black patients. Metabolic bone disease contributes significantly to morbidity in sickle cell disease; however, clinical guidelines for screening and treatment do not currently exist. Clinical care recommendations are provided to raise awareness, close health care gaps, and guide future research efforts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36314507,

title = {Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study},

author = {Deborah M Mitchell and Vibha Singhal and Abisayo Animashaun and Amita Bose and Brian Carmine and Fatima C Stanford and Thomas H Inge and Megan M Kelsey and Hang Lee and Mary L Bouxsein and Elaine W Yu and Miriam A Bredella and Madhusmita Misra},

doi = {10.1210/clinem/dgac634},

issn = {1945-7197},

year  = {2023},

date = {2023-03-01},

journal = {J Clin Endocrinol Metab},

volume = {108},

number = {4},

pages = {847--857},

abstract = {CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health.nnOBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth.nnMETHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture.nnRESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls.nnCONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36463566,

title = {Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN)},

author = {Karen P Jakubowski and Rachel E Koffer and Karen A Matthews and Sherri-Ann M Burnett-Bowie and Carol A Derby and Elaine W Yu and Robin Green and Rebecca C Thurston},

doi = {10.1002/jts.22896},

issn = {1573-6598},

year  = {2023},

date = {2023-02-01},

journal = {J Trauma Stress},

volume = {36},

number = {1},

pages = {167--179},

abstract = {Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36368466,

title = {The PYY/Y2R-deficient male mouse is not protected from bone loss due to Roux-en-Y gastric bypass},

author = {Bita Zahedi and Eileen J Daley and Daniel J Brooks and Michael Bruce and R Leigh Townsend and Hans-Rudolf Berthoud and Mary L Bouxsein and Elaine W Yu},

doi = {10.1016/j.bone.2022.116608},

issn = {1873-2763},

year  = {2023},

date = {2023-02-01},

journal = {Bone},

volume = {167},

pages = {116608},

abstract = {BACKGROUND: Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice.nnMETHODS: We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n = 8; KO: n = 9), with sham-operated mice (Sham; WT: n = 9; KO: n = 10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n = 7; KO: n = 5). RYGB or sham surgery was performed at 15-16 weeks of age, and mice sacrificed 21 weeks later. We characterized bone microarchitecture with micro-computed tomography (μCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey's adjustments for multiple comparisons.nnRESULTS: Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44 g; these groups weighed significantly less than the Sham surgery groups: 55-57 g. Trabecular BMD was 31-43 % lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19 %-23 %), thickness (22 %-30 %) and increased trabecular spacing (25 %-34 %) in WT and KO groups (p < 0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p ≤ 0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups.nnCONCLUSIONS: RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{697766,

title = {The PYY/Y2R-deficient male mouse is not protected from bone loss due to Roux-en-Y gastric bypass},

author = {Bita Zahedi and Eileen J Daley and Daniel J Brooks and Michael Bruce and R Leigh Townsend and Hans-Rudolf Berthoud and Mary L Bouxsein and Elaine W Yu},

url = {https://pubmed.ncbi.nlm.nih.gov/36368466/},

year  = {2023},

date = {2023-01-01},

journal = {Bone},

abstract = {Background: Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice. Methods: We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n = 8; KO: n = 9), with sham-operated mice (Sham; WT: n = 9; KO: n = 10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n = 7; KO: n = 5). RYGB or sham surgery was performed at 15-16 weeks of age, and mice sacrificed 21 weeks later. We characterized bone microarchitecture with micro-computed tomography (μCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey’s adjustments for multiple comparisons. Results: Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44 g; these groups weighed significantly less than the Sham surgery groups: 55-57 g. Trabecular BMD was 31-43 % lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19 %-23 %), thickness (22 %-30 %) and increased trabecular spacing (25 %-34 %) in WT and KO groups (p < 0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p <= 0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups. 

	Conclusions: RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37867730,

title = {Vascular deficits contributing to skeletal fragility in type 1 diabetes},

author = {Adina E Draghici and Bita Zahedi and J Andrew Taylor and Mary L Bouxsein and Elaine W Yu},

doi = {10.3389/fcdhc.2023.1272804},

issn = {2673-6616},

year  = {2023},

date = {2023-01-01},

journal = {Front Clin Diabetes Healthc},

volume = {4},

pages = {1272804},

abstract = {Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and  human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{697765,

title = {Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women’s Health Across the Nation (SWAN)},

author = {Karen P Jabukowski and Rachel E Koffer and Karen A Matthews and Sherri-Ann M Burnett-Bowie and Carol A Derby and Elaine W Yu and Robin Green and Rebecca C Thurston},

url = {https://pubmed.ncbi.nlm.nih.gov/36463566/},

year  = {2022},

date = {2022-01-01},

journal = {Journal of traumatic stress},

abstract = {Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women’s Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{697767,

title = {Secular Trends in the Pharmacologic Treatment of Osteoporosis and Malignancy-Related Bone Disease from 2009 to 2020},

author = {Sara Jane Cromer and Kristin M D’Silva and Elaine W Yu and Joan Landon and Rishi J Desai and Seoyoung C Kim},

url = {https://pubmed.ncbi.nlm.nih.gov/34100235/},

year  = {2022},

date = {2022-01-01},

journal = {Journal of general internal medicine},

volume = {37},

number = {8},

pages = {1917-1924},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688034,

title = {Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition.},

author = {A. S. Karlamangla and A Shieh and GA Greendale and E W Yu and SM Burnett-Bowie and PM Sluss and D Martin and A Morrison and J S Finkelstein},

year  = {2022},

date = {2022-01-01},

journal = {J Bone Miner Res},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688038,

title = {Disparities in Osteoporosis Care among Postmenopausal Women in the United States.},

author = {Karina N Ruiz-Estevesa and Jimmitti Teysira and Daria Schatoffa and Elaine W Yu and Sherri-Ann M Burnett-Bowie},

year  = {2022},

date = {2022-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688039,

title = {Zoledronic Acid-Associated Fanconi Syndrome in Patients with Cancer: A Report of 4 Cases.},

author = {Ignacio Portales-Castillo and David B Mount and Sagar Nigwekar and Elaine W Yu and Helmut Rennke and Shruti Gupta},

year  = {2022},

date = {2022-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{697767b,

title = {Secular Trends in the Pharmacologic Treatment of Osteoporosis and Malignancy-Related Bone Disease from 2009 to 2020},

author = {Sara Jane Cromer and Kristin M D’Silva and Elaine W Yu and Joan Landon and Rishi J Desai and Seoyoung C Kim},

url = {https://pubmed.ncbi.nlm.nih.gov/34100235/},

year  = {2022},

date = {2022-01-01},

journal = {Journal of general internal medicine},

volume = {37},

number = {8},

pages = {1917-1924},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688039b,

title = {Zoledronic Acid-Associated Fanconi Syndrome in Patients with Cancer: A Report of 4 Cases.},

author = {Ignacio Portales-Castillo and David B Mount and Sagar Nigwekar and Elaine W Yu and Helmut Rennke and Shruti Gupta},

year  = {2022},

date = {2022-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688032,

title = {Age-related changes in bone density, microarchitecture and strength in postmenopausal Black and White women: SWAN Longitudinal HR-pQCT Study.},

author = {Fjola Johannesdottir and Melissa S Putman and Sherri-Ann M Burnett-Bowie and Joel S Finkelstein and Elaine W Yu and Mary L Bouxsein},

year  = {2021},

date = {2021-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688037,

title = {Challenges and opportunities for osteoporosis care during the COVID-19 pandemic.},

author = {Sara J Cromer and Elaine W Yu},

year  = {2021},

date = {2021-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688027,

title = {Impact of sleeve gastrectomy on bone outcomes in adolescents vs. adults with obesity.},

author = {Miriam A Bredella and Nazanin Hazhir Karzar and Vibha Singhal and Amita Bose and Abisayo Animashaun and Deborah M Mitchell and Elaine W Yu and Madhusmita Misra},

year  = {2021},

date = {2021-01-01},

journal = {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%},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688029,

title = {Prescription Patterns of Osteoporosis Medications in Patients With Advanced CKD: A Retrospective Cohort Study.},

author = {Ignacio A Portales-Castillo and Cagri Aksu and Sophia Zhao and Ian Strohbehn and Meghan Sise and Elaine W Yu and Sagar U Nigwekar},

year  = {2021},

date = {2021-01-01},

journal = {Kidney Med.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688025,

title = {Risk of Incident Atrial Fibrillation with Zoledronic Acid Versus Denosumab: A Propensity Score-Matched Cohort Study},

author = {Kristin M D’Silva and Sara Jane Cromer and Elaine W Yu and Michael Fischer and Seoyoung C Kim},

year  = {2021},

date = {2021-01-01},

journal = {J Bone Miner Res},

volume = {36},

number = {1},

pages = {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. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688036,

title = {Vaccination for COVID-19 and relationship to osteoporosis care: Current evidence and suggested approaches.},

author = {Elena Tsourdi and Elaine W Yu and Suzanne M Jan Beur and Matthew T Drake},

year  = {2021},

date = {2021-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688024,

title = {Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men.},

author = {Anna Aulinas and Francisco J Guarda and Elaine W Yu and Melanie S Haines and Elisa Asanza and Lisseth Silva and Nicholas A Tritos and Joseph Verbalis and Karen K Miller and Elizabeth A Lawson},

year  = {2021},

date = {2021-01-01},

journal = {Neuroendocrinology},

volume = {111},

number = {1-2},

pages = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32663365,

title = {Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding},

author = {Katherine G Lindeman and Claire C Rushin and Michael C Cheney and Mary L Bouxsein and Matthew M Hutter and Elaine W Yu},

doi = {10.1002/jbmr.4112},

issn = {1523-4681},

year  = {2020},

date = {2020-11-01},

journal = {J Bone Miner Res},

volume = {35},

number = {11},

pages = {2132--2142},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32480409,

title = {Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men},

author = {Joel S Finkelstein and Hang Lee and Sherri-Ann M Burnett-Bowie and Karin Darakananda and Emily C Gentile and David W Goldstein and Sarah H Prizand and Laura M Krivicich and Alexander P Taylor and Kendra E Wulczyn and Benjamin Z Leder and Elaine W Yu},

doi = {10.1210/clinem/dgaa318},

issn = {1945-7197},

year  = {2020},

date = {2020-08-01},

journal = {J Clin Endocrinol Metab},

volume = {105},

number = {8},

pages = {2779--2788},

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.nnOBJECTIVE: To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men.nnDESIGN, 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).nnPRIMARY OUTCOMES: Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire.nnRESULTS: 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.nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32150549,

title = {Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial},

author = {Elaine W Yu and Liu Gao and Petr Stastka and Michael C Cheney and Jasmin Mahabamunuge and Mariam Torres Soto and Christopher B Ford and Jessica A Bryant and Matthew R Henn and Elizabeth L Hohmann},

doi = {10.1371/journal.pmed.1003051},

issn = {1549-1676},

year  = {2020},

date = {2020-03-01},

journal = {PLoS Med},

volume = {17},

number = {3},

pages = {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.nnMETHODS 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.nnCONCLUSIONS: 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.nnTRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688035,

title = {Bone Complications of Bariatric Surgery: Updates on Sleeve Gastrectomy, Fractures, and Interventions},

author = {Kristen M Beavers and Katelyn A Greene and Elaine W Yu},

year  = {2020},

date = {2020-01-01},

journal = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31090893,

title = {Fracture Risk After Roux-en-Y Gastric Bypass vs Adjustable Gastric Banding Among Medicare Beneficiaries},

author = {Elaine W Yu and Seoyoung C Kim and Daniel J Sturgeon and Katherine G Lindeman and Joel S Weissman},

doi = {10.1001/jamasurg.2019.1157},

issn = {2168-6262},

year  = {2019},

date = {2019-08-01},

journal = {JAMA Surg},

volume = {154},

number = {8},

pages = {746--753},

abstract = {IMPORTANCE: Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and may increase fracture risk, whereas substantial bone loss and increased fracture risk have not been reported after adjustable gastric banding (AGB). Previous studies have had little representation of patients aged 65 years or older, and it is currently unknown how age modifies fracture risk.nnOBJECTIVE: To compare fracture risk after RYGB and AGB procedures in a large, nationally representative cohort enriched for older adults.nnDESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort analysis used Medicare claims data from January 1, 2006, to December 31, 2014, from 42 345 severely obese adults, of whom 29 624 received RYGB and 12 721 received AGB. Data analysis was performed from April 2017 to November 2018.nnMAIN OUTCOMES AND MEASURES: The primary outcome was incident nonvertebral (ie, wrist, humerus, pelvis, and hip) fractures after RYGB and AGB surgery defined using a combination of International Classification of Diseases, Ninth Edition and Current Procedural Terminology 4 codes.nnRESULTS: Of 42 345 participants, 33 254 (78.5%) were women. With a mean (SD) age of 51 (12) years, recipients of RYGB were younger than AGB recipients (55 [12] years). Both groups had similar comorbidities, medication use, and health care utilization in the 365 days before surgery. Over a mean (SD) follow-up of 3.5 (2.1) years, 658 nonvertebral fractures were documented. The fracture incidence rate was 6.6 (95% CI, 6.0-7.2) after RYGB and 4.6 (95% CI, 3.9-5.3) after AGB, which translated to a hazard ratio (HR) of 1.73 (95% CI, 1.45-2.08) after multivariable adjustment. Site-specific analyses demonstrated an increased fracture risk at the hip (HR, 2.81; 95% CI, 1.82-4.49), wrist (HR, 1.70; 95% CI, 1.33-2.14), and pelvis (HR, 1.48; 95% CI, 1.08-2.07) among RYGB recipients. No significant interactions of fracture risk with age, sex, diabetes status, or race were found. In particular, adults 65 years and older showed similar patterns of fracture risk to younger adults. Sensitivity analyses using propensity score matching showed similar results (nonvertebral fracture: HR 1.75; 95% CI, 1.22-2.52).nnCONCLUSIONS AND RELEVANCE: This study of a large, US population-based cohort including a substantial population of older adults found a 73% increased risk of nonvertebral fracture after RYGB compared with AGB, including increased risk of hip, wrist, and pelvis fractures. Fracture risk was consistently increased among RYGB patients vs AGB across different subgroups, and to a similar degree among older and younger adults. Increased fracture risk appears to be an important unintended consequence of RYGB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30998999,

title = {Influence of soft tissue on bone density and microarchitecture measurements by high-resolution peripheral quantitative computed tomography},

author = {Signe Caksa and Amy Yuan and Sara E Rudolph and Elaine W Yu and Kristin L Popp and Mary L Bouxsein},

doi = {10.1016/j.bone.2019.04.008},

issn = {1873-2763},

year  = {2019},

date = {2019-07-01},

journal = {Bone},

volume = {124},

pages = {47--52},

abstract = {High-resolution peripheral quantitative computed tomography (HR-pQCT) is a non-invasive method of measuring volumetric bone mineral density (vBMD) and microarchitecture at the distal radius and tibia. With increasing use of this technology, it is crucial to understand the potential impact of overlying soft tissue on the accuracy of HR-pQCT measures. Thus, we examined the effects of a simulated increase in adiposity (via 6- and 12-mm thick layers of overlying circumferential fat) on HR-pQCT measures of a hydroxyapatite (HA) phantom and in women (n = 20, aged 18-75 years). In the phantom, increasing the amount of overlying fat tissue led to a corresponding decrease in the mean measured density for each HA rod. In women, fat-layering led to a decrease in total vBMD (-2.9 to -3.7%, p < 0.001), cortical vBMD (-1.4% to -5.5%, p < 0.001), and estimated failure load (-1.4 to -5.7%, p = 0.002) at the radius, with similar changes in the tibia. Trabecular microarchitectural measurements were also impacted by simulated adiposity, with fat-layering leading to decreased trabecular thickness and separation and increased trabecular number at the radius (Δ's = 5 to 12%) with more pronounced differences at the tibia (Δ's = 14 to 40%). At the tibia, fat-layering also led to decreased cortical thickness and increased cortical porosity. Altogether, these results demonstrate that overlying adipose tissue can lead to artifacts in bone measurements by HR-pQCT, resulting in an underestimation of vBMD and generally, an overestimation of bone microarchitecture impairment. Therefore, soft tissue artifact should be considered when interpreting HR-pQCT results, particularly in those with high BMI and/or marked changes in adiposity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30817009,

title = {Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant/restrictive food intake disorder},

author = {Melanie Schorr and Anne Drabkin and Micol S Rothman and Erinne Meenaghan and Gillian T Lashen and Margherita Mascolo and Ashlie Watters and Tara M Holmes and Kate Santoso and Elaine W Yu and Madhusmita Misra and Kamryn T Eddy and Anne Klibanski and Philip Mehler and Karen K Miller},

doi = {10.1111/cen.13960},

issn = {1365-2265},

year  = {2019},

date = {2019-06-01},

journal = {Clin Endocrinol (Oxf)},

volume = {90},

number = {6},

pages = {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.nnDESIGN: Cross-sectional: two centres.nnPATIENTS: A total of 103 men, 18-63 years: AN (n = 26), ARFID (n = 11), ATYP (n = 18), healthy controls (HC) (n = 48).nnMEASUREMENTS: 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.nnRESULTS: 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).nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30935764,

title = {Comparative effectiveness of gastric bypass versus gastric banding on acute care use for cardiovascular disease in adults with obesity},

author = {Y J Shimada and T Goto and Y Tsugawa and E W Yu and K Yoshida and S Homma and D F M Brown and K Hasegawa},

doi = {10.1016/j.numecd.2019.02.001},

issn = {1590-3729},

year  = {2019},

date = {2019-05-01},

journal = {Nutr Metab Cardiovasc Dis},

volume = {29},

number = {5},

pages = {518--526},

abstract = {BACKGROUND AND AIMS: Gastric bypass is known to have larger effects on weight and metabolism than gastric banding. However, scarce data exist as to whether the differences are translated into differential risks of cardiovascular disease (CVD)-related morbidities. The objective was to examine whether adults with obesity and CVD who underwent gastric bypass have a lower rate of acute care use (emergency department [ED] visit or unplanned hospitalization) for CVD than those with gastric banding.nnMETHODS AND RESULTS: We performed a comparative effectiveness study of gastric bypass versus banding among adults with obesity and CVD who underwent either surgery, using population-based [ED] and inpatient samples in California, Florida, and Nebraska from 2005 through 2011. The primary outcome was acute care use for CVD during a two-year postoperative period. We constructed negative binomial regression models to compare the event rate during sequential 6-month periods, using gastric banding group as the reference. We identified 11,229 adults with obesity and CVD who underwent gastric bypass and 3896 adults who had gastric banding. Patients with gastric bypass had significantly lower rate of the outcome compared to those with banding in the 7-12 months postoperative period (adjusted rate ratio [aRR] 0.77; 95% confidence interval [CI], 0.61-0.98; P = 0.03). The significant reduction in the rate persisted during 13-18 months (aRR 0.71; 95% CI, 0.57-0.90; P = 0.005) and 19-24 months (aRR 0.66; 95% CI, 0.52-0.82; P < 0.001) after bariatric surgery.nnCONCLUSION: In this population-based comparative effectiveness study of adults with obesity and CVD, the rate of acute care use for CVD was lower after gastric bypass compared to gastric banding.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30357327,

title = {Bariatric surgery is associated with lower risk of acute care use for cardiovascular disease in obese adults},

author = {Yuichi J Shimada and Koichiro Gibo and Yusuke Tsugawa and Tadahiro Goto and Elaine W Yu and Hiroyasu Iso and David F M Brown and Kohei Hasegawa},

doi = {10.1093/cvr/cvy266},

issn = {1755-3245},

year  = {2019},

date = {2019-03-01},

journal = {Cardiovasc Res},

volume = {115},

number = {4},

pages = {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.nnMETHODS 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).nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30281863,

title = {Cortical Bone Material Strength Index and Bone Microarchitecture in Postmenopausal Women With Atypical Femoral Fractures},

author = {Kristin L Popp and Signe Caksa and Adriana Martinez-Betancourt and Amy Yuan and Joy Tsai and Elaine W Yu and Mary L Bouxsein},

doi = {10.1002/jbmr.3590},

issn = {1523-4681},

year  = {2019},

date = {2019-01-01},

journal = {J Bone Miner Res},

volume = {34},

number = {1},

pages = {75--82},

abstract = {Atypical femoral fractures are rare fractures that occur in the subtrochanteric or diaphyseal region of the femur with minimal or no trauma. Though the association of atypical femoral fractures (AFFs) and bisphosphonate (BP) use is a growing concern in the management of osteoporosis, currently there is little knowledge about which patients may be at risk for an atypical femoral fracture. Given that these fractures initiate in the femoral cortex, we aimed to determine whether cortical bone tissue properties (bone material strength index; BMSi), as measured by in vivo impact microindentation, are altered in atypical fracture patients. We also aimed to identify factors associated with the BMSi measurements. We enrolled postmenopausal women with recent AFFs (n = 15) or hip fractures (Hip Fxs; n = 20), long-term (>5 years) BP users (n = 30), and treatment naïve controls (n = 88). We measured total hip and femoral neck BMD by DXA, cortical bone microstructure at the distal tibia by HR-pQCT, and BMSi at the midtibia by impact microindentation. BMSi values were similar in all groups, with no effects of long-term BP use or lower values in patients with AFFs or Hip Fxs, even after multivariable adjustment. BMSi measurements were independent of age, femoral BMD, duration of BP treatment, vitamin D level, and cortical bone microstructure, including cortical porosity and cortical tissue mineral density. In conclusion, impact microindentation values are not negatively affected by long-term BP use and do not appear to discriminate individuals who suffer AFFs. Thus, our results do not support clinical use of impact microindentation to identify those at risk for AFFs. This remains to be verified in larger studies. © 2018 American Society for Bone and Mineral Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30219833,

title = {Longitudinal 5-Year Evaluation of Bone Density and Microarchitecture After Roux-en-Y Gastric Bypass Surgery},

author = {Katherine G Lindeman and Logan B Greenblatt and Caroline Rourke and Mary L Bouxsein and Joel S Finkelstein and Elaine W Yu},

doi = {10.1210/jc.2018-01496},

issn = {1945-7197},

year  = {2018},

date = {2018-11-01},

journal = {J Clin Endocrinol Metab},

volume = {103},

number = {11},

pages = {4104--4112},

abstract = {CONTEXT: Bone health declines in the initial years after Roux-en-Y gastric bypass (RYGB), but long-term skeletal effects are unclear.nnOBJECTIVE: To document longitudinal changes in bone mineral density (BMD) and microarchitecture 5 years after RYGB.nnDESIGN, SETTING, AND PARTICIPANTS: Prospective 5-year observational study of 21 adults with severe obesity receiving RYGB at an academic medical center.nnMAIN OUTCOME MEASURES: Spine and hip areal BMD were measured by dual-energy X-ray absorptiometry, and trabecular volumetric BMD (vBMD) of the spine was assessed by quantitative CT (QCT). We measured vBMD and microarchitecture of the distal radius and tibia by high-resolution peripheral QCT in a subset of subjects. Serum type I collagen C-terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (P1NP) were also measured.nnRESULTS: Areal BMD declined by -7.8% ± 7.6% at the spine and -15.3% ± 6.3% at the total hip by 5 years after RYGB (P ≤ 0.001), although the rate of bone loss slowed in later years. Trabecular spine vBMD decreased by -12.1% ± 12.3% by 5 years (P ≤ 0.001). At peripheral sites, vBMD continued to decrease steadily throughout 5 years, with parallel declines in cortical and trabecular microarchitecture, leading to decreases in estimated failure load of -20% and -13% at the radius and tibia, respectively (P < 0.001). Five years after RYGB, CTX and P1NP were 150% and 34% above baseline (P < 0.001 and P = 0.017, respectively).nnCONCLUSIONS: Sustained high-turnover bone loss and bone microarchitectural deterioration occur in the 5 years after RYGB. Adults receiving RYGB warrant assessment of bone health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29603359,

title = {Bariatric Surgery: Weighing In on Bone Loss},

author = {Elaine W Yu},

doi = {10.1002/jbmr.3432},

issn = {1523-4681},

year  = {2018},

date = {2018-06-01},

journal = {J Bone Miner Res},

volume = {33},

number = {6},

pages = {973--974},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29115684,

title = {Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures},

author = {Tamara D Rozental and Kempland C Walley and Serkalem Demissie and Signe Caksa and Adriana Martinez-Betancourt and Amber M Parker and Joy N Tsai and Elaine W Yu and Mary L Bouxsein},

doi = {10.1002/jbmr.3338},

issn = {1523-4681},

year  = {2018},

date = {2018-04-01},

journal = {J Bone Miner Res},

volume = {33},

number = {4},

pages = {621--626},

abstract = {We tested whether cortical bone tissue properties assessed by in vivo impact microindentation would distinguish postmenopausal women with recent distal radius (DRF) or hip fracture (HF) from nonfracture controls (CONT). We enrolled postmenopausal women with recent DRF (n = 57), HF (n = 41), or CONT (n = 93), and used impact microindentation to assess bone material strength index (BMSi) at the anterior surface of the mid-tibia diaphysis. Areal bone mineral density (aBMD) (g/cm ) of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). HF and DRF subjects had significantly lower BMD than CONT at all sites (-5.6% to -8.2%, p < 0.001 for all). BMSi was 4% lower in DRF compared to CONT (74.36 ± 8.77 versus 77.41 ± 8.79, p = 0.04). BMSi was similarly lower in HF versus CONT, but the difference did not reach statistical significance (74.62 ± 8.47 versus 77.41 ± 8.79, p = 0.09). Lower BMSi was associated with increased risk of DRF (unadjusted OR, 1.43; 95% CI, 1.02 to 2.00, per SD decrease, p = 0.04), and remained statistically significant after adjustment for age, age and BMI, and age, BMI, and FN BMD (OR = 1.48 to 1.55). Lower BMSi tended to be associated with HF, but only reached borderline significance (unadjusted OR = 1.39; 95% CI, 0.96 to 2.01, p = 0.08). These results provide strong rationale for future investigations aimed at assessing whether BMSi can predict fracture in prospective studies and improve identification of women at risk for fragility fractures. © 2017 American Society for Bone and Mineral Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28780520,

title = {Bone microarchitecture and estimated bone strength in men with active acromegaly},

author = {Paula P B Silva and Fatemeh G Amlashi and Elaine W Yu and Karen J Pulaski-Liebert and Anu V Gerweck and Pouneh K Fazeli and Elizabeth Lawson and Lisa B Nachtigall and Beverly M K Biller and Karen K Miller and Anne Klibanski and Mary Bouxsein and Nicholas A Tritos},

doi = {10.1530/EJE-17-0468},

issn = {1479-683X},

year  = {2017},

date = {2017-11-01},

journal = {Eur J Endocrinol},

volume = {177},

number = {5},

pages = {409--420},

abstract = {CONTEXT: Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA).nnOBJECTIVE: To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls.nnDESIGN AND SUBJECTS: Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls).nnOUTCOME MEASURES: Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia.nnRESULTS: aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( < 0.0001), cortical thickness ( = 0.0038), cortical pore volume ( < 0.0001) and cortical porosity ( = 0.0008), but lower trabecular bone density ( = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density ( = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD.nnCONCLUSIONS: Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28251687,

title = {Fracture Risk After Bariatric Surgery: Roux-en-Y Gastric Bypass Versus Adjustable Gastric Banding},

author = {Elaine W Yu and Moa P Lee and Joan E Landon and Katherine G Lindeman and Seoyoung C Kim},

doi = {10.1002/jbmr.3101},

issn = {1523-4681},

year  = {2017},

date = {2017-06-01},

journal = {J Bone Miner Res},

volume = {32},

number = {6},

pages = {1229--1236},

abstract = {The long-term consequences of bariatric surgery on fracture risk are unclear but are likely to vary by procedure type. In physiologic studies, Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) have differential effects on rates of bone loss. Therefore, our objective was to compare fracture risk in obese adults after RYGB and AGB procedures. Using claims data from a US commercial health plan, we analyzed rates of nonvertebral fractures within a propensity score-matched cohort (n = 15,032) of morbidly obese adults who received either RYGB or AGB surgery between 2005 and 2013. A total of 281 nonvertebral fractures occurred during a mean follow-up time of 2.3 ± 1.9 years. RYGB patients had an increased risk of nonvertebral fracture (hazard ratio [HR] = 1.43, 95% confidence interval [CI] 1.13-1.81) compared with AGB patients. In fracture site-specific analyses, RYGB patients had increased risk of fracture at the hip (HR = 1.54, 95% CI 1.03-2.30) and wrist (HR = 1.45, 95% CI 1.01-2.07). Nonvertebral fracture risk associated with RYGB manifested >2 years after surgery and increased in subsequent years, with the highest risk in the fifth year after surgery (HR = 3.91, 95% CI 1.58-9.64). In summary, RYGB is associated with a 43% increased risk of nonvertebral fracture compared with AGB, with risk increasing >2 years after surgery. Fracture risk should be considered in risk/benefit discussions of bariatric surgery, particularly among patients with high baseline risk of osteoporosis who are deciding between RYGB and AGB procedures. © 2017 American Society for Bone and Mineral Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27958659,

title = {Differences in Trabecular Microstructure Between Black and White Women Assessed by Individual Trabecular Segmentation Analysis of HR-pQCT Images},

author = {Melissa S Putman and Elaine W Yu and David Lin and Karin Darakananda and Joel S Finkelstein and Mary L Bouxsein},

doi = {10.1002/jbmr.3060},

issn = {1523-4681},

year  = {2017},

date = {2017-05-01},

journal = {J Bone Miner Res},

volume = {32},

number = {5},

pages = {1100--1108},

abstract = {Black women have lower fracture risk compared with white women, which may be partly explained by improved volumetric bone mineral density (vBMD) and bone microarchitecture primarily within the cortical bone compartment. To determine if there are differences in trabecular microstructure, connectivity, and alignment according to race/ethnicity, we performed individual trabecular segmentation (ITS) analyses on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia in 273 peri- and postmenopausal black (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation in Boston. Unadjusted analyses showed that black women had greater trabecular plate volume fraction, plate thickness, plate number density, and plate surface area along with greater axial alignment of trabeculae, whereas white women had greater trabecular rod tissue fraction (p < 0.05 for all). Adjustment for clinical covariates augmented these race/ethnicity-related differences in plates and rods, such that white women had greater trabecular rod number density and rod-rod connectivity, whereas black women continued to have superior plate structural characteristics and axial alignment (p < 0.05 for all). These differences remained significant after adjustment for hip BMD and trabecular vBMD. In conclusion, black women had more plate-like trabecular morphology and higher axial alignment of trabeculae, whereas white women had more rod-like trabeculae. These differences may contribute to the improved bone strength and lower fracture risk observed in black women. © 2016 American Society for Bone and Mineral Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28043896,

title = {Marrow adipose tissue composition in adults with morbid obesity},

author = {Elaine W Yu and Logan Greenblatt and Alireza Eajazi and Martin Torriani and Miriam A Bredella},

doi = {10.1016/j.bone.2016.12.018},

issn = {1873-2763},

year  = {2017},

date = {2017-04-01},

journal = {Bone},

volume = {97},

pages = {38--42},

abstract = {Patients with type 2 diabetes mellitus (T2DM) have increased fracture risk despite normal or increased bone mineral density (BMD). Elevations in marrow adipose tissue (MAT) and declines in MAT unsaturation are both associated with increased skeletal fragility. The objective of our study was to characterize the quantity and composition of MAT in adults with morbid obesity and T2DM, and to evaluate determinants of MAT. We studied 21 adults with morbid obesity prior to bariatric surgery, 8 of whom had T2DM. All subjects underwent 1H-MR spectroscopy of the lumbar spine and femur for assessment of MAT and dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) of the lumbar spine and hip for assessment of areal BMD (aBMD) and volumetric BMD (vBMD). Visceral (VAT) and subcutaneous adipose tissue (SAT) were quantified by CT at L1-L2. Subjects with T2DM had higher vBMD of the femoral neck and higher total MAT at the lumbar spine and femoral metaphysis compared to non-diabetic controls (p≤0.04). Lipid unsaturation index (UI) was significantly lower at the femoral diaphysis in T2DM (p=0.03). Within the entire cohort, HbA1c was positively associated with MAT (p≤0.03), and age was associated with higher MAT and lower MAT unsaturation (p≤0.05). Lumbar spine vBMD was inversely associated with lumbar spine MAT (p=0.04). There was an inverse association between SAT and diaphyseal MAT (p<0.05) while there were no associations with VAT. Subjects with morbid obesity and T2DM have higher MAT with a lower proportion of unsaturated lipids, despite higher femoral neck vBMD. MAT is positively associated with age and HbA1c, and inversely associated with vBMD, suggesting that MAT may serve as an imaging biomarker of skeletal health and metabolic risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27871812,

title = {Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density and marrow adipose tissue},

author = {Miriam A Bredella and Logan B Greenblatt and Alireza Eajazi and Martin Torriani and Elaine W Yu},

doi = {10.1016/j.bone.2016.11.014},

issn = {1873-2763},

year  = {2017},

date = {2017-02-01},

journal = {Bone},

volume = {95},

pages = {85--90},

abstract = {Bariatric surgery is associated with bone loss but skeletal consequences may differ between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the two most commonly performed bariatric procedures. Furthermore, severe weight loss is associated with high marrow adipose tissue (MAT); however, MAT is also increased in visceral adiposity. The purpose of our study was to determine the effects of RYGB and SG on BMD and MAT. We hypothesized that both bariatric procedures would lead to a decrease in BMD and MAT. We studied 21 adults with morbid obesity (mean BMI 44.1±5.1kg/m) prior to and 12months after RYGB (n=11) and SG (n=10). All subjects underwent DXA and QCT of the lumbar spine and hip to assess aBMD and vBMD. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified at L1-L2. MAT of the lumbar spine and femur was assessed by 1H-MR spectroscopy. Calcitropic hormones and bone turnover markers were determined. At 12months after surgery, mean weight and abdominal fat loss was similar between the RYGB and SG groups. Mean serum calcium, 25(OH)-vitamin D, and PTH levels were unchanged after surgery and within the normal range in both groups. Bone turnover markers P1NP and CTX increased within both groups and P1NP increased to a greater extent in the RYGB group (p=0.03). There were significant declines from baseline in spine aBMD and vBMD within the RYGB and SG groups, although the changes were not significantly different between groups (p=0.3). Total hip and femoral neck aBMD by DXA decreased to a greater extent in the RYGB than the SG group (p<0.04) although the change in femoral vBMD by QCT was not significantly different between groups (p>0.2). MAT content of the lumbar spine and femoral diaphysis did not change from baseline in the RYGB group but increased after SG (p=0.03). Within the SG group, 12-month change in weight and VAT were positively associated with 12-month change in MAT (p<0.04), suggesting that subjects with less weight and VAT loss had higher MAT. In conclusion, RYGB and SG are associated with declines in lumbar spine BMD, however, the changes are not significantly different between the groups. RYGB may be associated with greater decline of aBMD at the total hip and femoral neck compared to SG. MAT content increased after SG and this was associated with lower weight and VAT loss.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28239652,

title = {Estrogens regulate glycosylation of IgG in women and men},

author = {Altan Ercan and Wendy M Kohrt and Jing Cui and Kevin D Deane and Marija Pezer and Elaine W Yu and Jonathan S Hausmann and Harry Campbell and Ursula B Kaiser and Pauline M Rudd and Gordan Lauc and James F Wilson and Joel S Finkelstein and Peter A Nigrovic},

doi = {10.1172/jci.insight.89703},

issn = {2379-3708},

year  = {2017},

date = {2017-02-01},

journal = {JCI Insight},

volume = {2},

number = {4},

pages = {e89703},

abstract = {The immunologic potency of IgG is modulated by glycosylation, but mechanisms regulating this process are undefined. A role for sex hormones is suggested by differences in IgG glycans between women and men, most prominently with respect to galactose. We therefore assessed IgG galactosylation in 713 healthy adults from 2 cohorts as well as in 159 subjects from 4 randomized controlled studies of endocrine manipulation: postmenopausal women receiving conjugated estrogens, raloxifene, or placebo; premenopausal women deprived of gonadal hormones with leuprolide and treated with estradiol or placebo; men deprived of gonadal hormones with goserelin and given testosterone or placebo; and men deprived of gonadal hormones with goserelin and given testosterone or placebo together with anastrozole to block conversion of testosterone to estradiol. Menopause was associated with an increase in agalactosylated IgG glycans, particularly in the most abundant fucosylated nonbisected (G0F) glycoform. Conjugated estrogens and raloxifene reduced G0F glycans in postmenopausal women, while in premenopausal women leuprolide increased G0F glycans in a manner reversed by estradiol. Among men, goserelin increased G0F glycans, an effect blocked by testosterone through conversion to estradiol. These results establish estrogens as an in vivo modulator of IgG galactosylation in both women and men, defining a pathway by which sex modulates immunity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27611507,

title = {Idiopathic tumoral calcinosis-like lesion in the lower cervical spine causing acute central cord syndrome: case report},

author = {Ahmad Al-Sukaini and Nuno Rui Paulino Pereira and Elaine W Yu and Ivan Chebib and Miriam A Bredella and Joseph Schwab},

doi = {10.3171/2016.6.SPINE151565},

issn = {1547-5646},

year  = {2017},

date = {2017-01-01},

journal = {J Neurosurg Spine},

volume = {26},

number = {1},

pages = {97--102},

abstract = {A 57-year-old male presented with recurrent falls, bilateral lower-limb paresthesia, and severe neck pain. Imaging revealed a mass compressing his spinal cord. He was admitted for further workup for spinal cord compression. Within 24 hours of admission, he developed upper-extremity weakness while maintaining lower-extremity function. He underwent urgent decompression of his spinal cord. During exposure, a white, creamy odorless substance was noted. This same substance was found under pressure within the spinal canal. The mass was grossly removed, and the patient's weakness improved postoperatively. Based on the clinical picture, intraoperative presentation, and final histological examination, idiopathic tumoral calcinosis-like lesion was considered as the most appropriate diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26806052,

title = {Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass},

author = {Elaine W Yu and Jill S Carmody and Daniel J Brooks and Scott LaJoie and Lee M Kaplan and Mary L Bouxsein},

doi = {10.1016/j.bone.2016.01.017},

issn = {1873-2763},

year  = {2016},

date = {2016-04-01},

journal = {Bone},

volume = {85},

pages = {23--28},

abstract = {Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB-treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26901812,

title = {Gonadal steroid-dependent effects on bone turnover and bone mineral density in men},

author = {Joel S Finkelstein and Hang Lee and Benjamin Z Leder and Sherri-Ann M Burnett-Bowie and David W Goldstein and Christopher W Hahn and Sarah C Hirsch and Alex Linker and Nicholas Perros and Andrew B Servais and Alexander P Taylor and Matthew L Webb and Jonathan M Youngner and Elaine W Yu},

doi = {10.1172/JCI84137},

issn = {1558-8238},

year  = {2016},

date = {2016-03-01},

journal = {J Clin Invest},

volume = {126},

number = {3},

pages = {1114--1125},

abstract = {BACKGROUND: Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.nnMETHODS: One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.nnRESULTS: As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.nnCONCLUSIONS: Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.nnTRIAL REGISTRATION: ClinicalTrials.gov, NCT00114114.nnFUNDING: AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26600045,

title = {Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients With Type 2 Diabetes},

author = {Elaine W Yu and Marlene Wewalka and Su-Ann Ding and Donald C Simonson and Kathleen Foster and Jens J Holst and Ashley Vernon and Allison B Goldfine and Florencia Halperin},

doi = {10.1210/jc.2015-3437},

issn = {1945-7197},

year  = {2016},

date = {2016-02-01},

journal = {J Clin Endocrinol Metab},

volume = {101},

number = {2},

pages = {714--722},

abstract = {CONTEXT: Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery.nnOBJECTIVE: To evaluate effects of RYGB and LAGB on fasting and postprandial indices of bone remodeling.nnDESIGN AND SETTING: Ancillary investigation of a prospective study at 2 academic institutions.nnPARTICIPANTS: Obese adults aged 21-65 years with type 2 diabetes who underwent RYGB (n = 11) or LAGB (n = 8).nnOUTCOMES: Serum C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and PTH were measured during a mixed meal tolerance test at baseline, 10 days and 1 year after surgery. Changes in 25-hydroxyvitamin D, polypeptide YY (PYY), glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and insulin were also assessed.nnRESULTS: Fasting CTX increased 10 days after RYGB but not LAGB (+69 ± 23% vs +12±12%, P < .001), despite comparable weight loss at that time. By 1 year, fasting CTX and P1NP increased more after RYGB than LAGB (CTX +221 ± 60% vs +15 ± 6%, P<0.001; P1NP +93 ± 25% vs -9 ± 10%, P < .001) and weight loss was greater with RYGB. Changes in CTX were independent of PTH and 25-hydroxyvitamin D but were associated with increases in fasting PYY. Postprandial suppression of CTX was more pronounced after RYGB than LAGB at 10 days and 1 year postoperatively.nnCONCLUSIONS: RYGB is accompanied by early increases in fasting indices of bone remodeling, independent of weight loss or changes in PTH or 25-hydroxyvitamin D. LAGB did not affect bone markers. PYY and other enterohormonal signals may play a role in RYGB-specific skeletal changes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25646793,

title = {Two-year changes in bone density after Roux-en-Y gastric bypass surgery},

author = {Elaine W Yu and Mary L Bouxsein and Melissa S Putman and Elizabeth L Monis and Adam E Roy and Janey S A Pratt and W Scott Butsch and Joel S Finkelstein},

doi = {10.1210/jc.2014-4341},

issn = {1945-7197},

year  = {2015},

date = {2015-04-01},

journal = {J Clin Endocrinol Metab},

volume = {100},

number = {4},

pages = {1452--1459},

abstract = {CONTEXT: Bariatric surgery is increasingly popular but may lead to metabolic bone disease.nnOBJECTIVE: The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.nnDESIGN AND SETTING: This was a prospective cohort study conducted at an academic medical center.nnPARTICIPANTS: The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.nnOUTCOMES: We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.nnRESULTS: Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (-37 ± 3 vs -5 ± 3 kg [ mean ± SEM]; P < .001). At 24 months, BMD was 5-7% lower at the spine and 6-10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.nnCONCLUSIONS: Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25398431,

title = {Defects in cortical microarchitecture among African-American women with type 2 diabetes},

author = {E W Yu and M S Putman and N Derrico and G Abrishamanian-Garcia and J S Finkelstein and M L Bouxsein},

doi = {10.1007/s00198-014-2927-7},

issn = {1433-2965},

year  = {2015},

date = {2015-02-01},

journal = {Osteoporos Int},

volume = {26},

number = {2},

pages = {673--679},

abstract = {SUMMARY: Patients with type 2 diabetes mellitus (DM2) have increased fracture risk. We found that African-American women with DM2 have increased cortical porosity and lower cortical bone density at the radius than non-diabetic controls. These cortical deficits are associated with hyperglycemia and may contribute to skeletal fragility associated with DM2.nnINTRODUCTION: Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure.nnMETHODS: We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR.nnRESULTS: Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=-0.54, p=0.018).nnCONCLUSIONS: DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further, our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}