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KARL INSOGNA

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https://www.readbyqxmd.com/read/28816930/associations-among-circulating-csf-1-estrogen-and-bone-mineral-density-in-postmenopausal-women-results-from-a-randomized-placebo-controlled-trial
#1
Andrea V Haas, Elaine Cong, Christine A Simpson, Nitin Sukumar, Yanhong Deng, Karl L Insogna
OBJECTIVE: This study addresses the relationship between circulating levels of colony-stimulating factor 1 (CSF-1) and rates of postmenopausal bone loss. The purpose was to test the hypothesis that CSF-1 levels would correlate with the rate of bone loss in estrogen-deficient woman. We further hypothesized that estrogen replacement would eliminate this association. METHODS: This was an ancillary study to the parent Kronos Early Estrogen Prevention Study (KEEPS)-a 4-year randomized placebo-controlled study that evaluated the effects of estrogen therapy on cardiovascular endpoints...
August 14, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28803675/the-yale-fitness-intervention-trial-in-female-cancer-survivors-cardiovascular-and-physiological-outcomes
#2
M Tish Knobf, Sangchoon Jeon, Barbara Smith, Lyndsay Harris, Siobhan Thompson, Mitchel R Stacy, Karl Insogna, Albert J Sinusas
BACKGROUND: Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors. OBJECTIVE: To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. METHODS: Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group...
August 10, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28791343/breast-cancer-associated-gene-3-interacts-with-rac1-and-augments-nf-%C3%AE%C2%BAb-signaling-in-vitro-but-has-no-effect-on-rankl-induced-bone-resorption-in-vivo
#3
Chen Yao, Kuan-Ping Yu, William Philbrick, Ben-Hua Sun, Christine Simpson, Changqing Zhang, Karl Insogna
Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-κB (NF-κB) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-κB signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-κB signaling in vitro...
October 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28655174/diagnosis-and-management-of-osteopetrosis-consensus-guidelines-from-the-osteopetrosis-working-group
#4
Calvin C Wu, Michael J Econs, Linda A DiMeglio, Karl L Insogna, Michael A Levine, Paul J Orchard, Weston P Miller, Anna Petryk, Eric T Rush, Dolores M Shoback, Leanne M Ward, Lynda E Polgreen
Background: Osteopetrosis encompasses a group of rare metabolic bone diseases characterized by impaired osteoclast activity or development, resulting in high bone mineral density. Existing guidelines focus on treatment of the severe infantile forms with hematopoietic cell transplantation (HCT) but do not address the management of patients with less severe forms for whom HCT is not the standard of care. Therefore, our objective was to develop expert consensus guidelines for the management of these patients...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28492492/the-effect-of-dietary-glycemic-properties-on-markers-of-inflammation-insulin-resistance-and-body-composition-in-postmenopausal-american-women-an-ancillary-study-from-a-multicenter-protein-supplementation-trial
#5
Violeta Stojkovic, Christine A Simpson, Rebecca R Sullivan, Anna Maria Cusano, Jane E Kerstetter, Anne M Kenny, Karl L Insogna, Jessica D Bihuniak
Controversy exists as to whether high glycemic index/glycemic load (GI/GL) diets increase the risk of chronic inflammation, which has been postulated as a pathogenic intermediary between such diets and age-related alterations in body composition and insulin resistance. We conducted an ancillary study to a randomized, double-blind trial comparing the effects of a whey protein supplement (PRO, n = 38) and a maltodextrin supplement (CHO, n = 46) on bone density to evaluate the impact of a calibrated increase in GI/GL on inflammation, insulin resistance, and body composition in a healthy aging population...
May 11, 2017: Nutrients
https://www.readbyqxmd.com/read/28404575/dietary-protein-and-bone-health-a-systematic-review-and-meta-analysis-from-the-national-osteoporosis-foundation
#6
REVIEW
Marissa M Shams-White, Mei Chung, Mengxi Du, Zhuxuan Fu, Karl L Insogna, Micaela C Karlsen, Meryl S LeBoff, Sue A Shapses, Joachim Sackey, Taylor C Wallace, Connie M Weaver
Background: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life.Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults.Design: Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining 1) the effects of "high versus low" protein intake or 2) dietary protein's synergistic effect with Ca±D intake on bone health outcomes...
June 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28326356/effect-of-four-monthly-doses-of-a-human-monoclonal-anti-fgf23-antibody-krn23-on-quality-of-life-in-x-linked-hypophosphatemia
#7
Mary D Ruppe, Xiaoping Zhang, Erik A Imel, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/27935736/pioglitazone-and-risk-for-bone-fracture-safety-data-from-a-randomized-clinical-trial
#8
RANDOMIZED CONTROLLED TRIAL
Catherine M Viscoli, Silvio E Inzucchi, Lawrence H Young, Karl L Insogna, Robin Conwit, Karen L Furie, Mark Gorman, Michael A Kelly, Anne M Lovejoy, Walter N Kernan
Context: Pioglitazone reduces cardiovascular risk in nondiabetic patients after an ischemic stroke or transient ischemic attack (TIA) but is associated with increased risk for bone fracture. Objective: To characterize fractures associated with pioglitazone by location, mechanism, severity, timing, and sex. Design, Setting, and Patients: Patients were 3876 nondiabetic participants in the Insulin Resistance Intervention after Stroke trial randomized to pioglitazone or placebo and followed for a median of 4...
March 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27338702/hypophosphatemia-promotes-lower-rates-of-muscle-atp-synthesis
#9
Dominik H Pesta, Dimitrios N Tsirigotis, Douglas E Befroy, Daniel Caballero, Michael J Jurczak, Yasmeen Rahimi, Gary W Cline, Sylvie Dufour, Andreas L Birkenfeld, Douglas L Rothman, Thomas O Carpenter, Karl Insogna, Kitt Falk Petersen, Clemens Bergwitz, Gerald I Shulman
Hypophosphatemia can lead to muscle weakness and respiratory and heart failure, but the mechanism is unknown. To address this question, we noninvasively assessed rates of muscle ATP synthesis in hypophosphatemic mice by using in vivo saturation transfer [(31)P]-magnetic resonance spectroscopy. By using this approach, we found that basal and insulin-stimulated rates of muscle ATP synthetic flux (VATP) and plasma inorganic phosphate (Pi) were reduced by 50% in mice with diet-induced hypophosphatemia as well as in sodium-dependent Pi transporter solute carrier family 34, member 1 (NaPi2a)-knockout (NaPi2a(-/-)) mice compared with their wild-type littermate controls...
October 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27312397/the-liver-throws-the-skeleton-a-bone-resorption-factor
#10
Chuhan Chung, Karl L Insogna
No abstract text is available yet for this article.
September 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27124896/longitudinal-increase-in-vitamin-d-binding-protein-levels-after-initiation-of-tenofovir-lamivudine-efavirenz-among-individuals-with-hiv
#11
Evelyn Hsieh, Liana Fraenkel, Yang Han, Weibo Xia, Karl L Insogna, Michael T Yin, Ting Zhu, Xinqi Cheng, Taisheng Li
OBJECTIVE: To examine longitudinal change in vitamin D binding protein (DBP) levels during the first year after initiation of tenofovir disoproxil fumarate (TDF)/lamivudine/efavirenz and compare these findings with concurrent changes in markers of skeletal metabolism. DESIGN: Secondary analysis of plasma samples collected from an ongoing multicenter clinical trial. METHODS: Plasma samples collected at 0, 24, and 48 weeks after initiation of TDF + lamivudine + efavirenz from 134 adult participants enrolled in a multicenter randomized trial were analyzed...
July 31, 2016: AIDS
https://www.readbyqxmd.com/read/26850265/effect-of-a-randomized-controlled-exercise-trial-on-bone-outcomes-influence-of-adjuvant-endocrine-therapy
#12
RANDOMIZED CONTROLLED TRIAL
M Tish Knobf, Sangchoon Jeon, Barbara Smith, Lyndsay Harris, Jane Kerstetter, A Siobhan Thompson, Karl Insogna
Bone loss is a significant clinical problem for female cancer survivors (FCS) and increases fracture risk. The aim of the Yale Fitness Intervention Trial (Yale FIT) was to determine the effects of a 12-month aerobic-resistance exercise intervention compared to a home-based physical activity group on bone outcomes [bone mineral density (BMD)] and biomarkers bone turnover). Early postmenopausal FCS (N = 154) were randomized to the exercise intervention (3 times/week) or to a home-based physical activity group...
February 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/26496249/deletion-of-rac-in-mature-osteoclasts-causes-osteopetrosis-an-age-dependent-change-in-osteoclast-number-and-a-reduced-number-of-osteoblasts-in-vivo
#13
Meiling Zhu, Ben-Hua Sun, Katarzyna Saar, Christine Simpson, Nancy Troiano, Sarah L Dallas, LeAnn M Tiede-Lewis, Erin Nevius, João P Pereira, Robert S Weinstein, Steven M Tommasini, Karl L Insogna
Rac1 and Rac2 are thought to have important roles in osteoclasts. Therefore, mice with deletion of both Rac1 and Rac2 in mature osteoclasts (DKO) were generated by crossing Rac1(flox/flox) mice with mice expressing Cre in the cathepsin K locus and then mating these animals with Rac2(-/-) mice. DKO mice had markedly impaired tooth eruption. Bone mineral density (BMD) was increased 21% to 33% in 4- to 6-week-old DKO mice at all sites when measured by dual-energy X-ray absorptiometry (DXA) and serum cross-linked C-telopeptide (CTx) was reduced by 52%...
April 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/26411686/agrp-neurons-regulate-bone-mass
#14
Jae Geun Kim, Ben-Hua Sun, Marcelo O Dietrich, Marco Koch, Gang-Qing Yao, Sabrina Diano, Karl Insogna, Tamas L Horvath
The hypothalamus has been implicated in skeletal metabolism. Whether hunger-promoting neurons of the arcuate nucleus impact the bone is not known. We generated multiple lines of mice to affect AgRP neuronal circuit integrity. We found that mice with Ucp2 gene deletion, in which AgRP neuronal function was impaired, were osteopenic. This phenotype was rescued by cell-selective reactivation of Ucp2 in AgRP neurons. When the AgRP circuitry was impaired by early postnatal deletion of AgRP neurons or by cell autonomous deletion of Sirt1 (AgRP-Sirt1(-/-)), mice also developed reduced bone mass...
October 6, 2015: Cell Reports
https://www.readbyqxmd.com/read/26321681/phosphoenolpyruvate-is-a-metabolic-checkpoint-of-anti-tumor-t-cell-responses
#15
Ping-Chih Ho, Jessica Dauz Bihuniak, Andrew N Macintyre, Matthew Staron, Xiaojing Liu, Robert Amezquita, Yao-Chen Tsui, Guoliang Cui, Goran Micevic, Jose C Perales, Steven H Kleinstein, E Dale Abel, Karl L Insogna, Stefan Feske, Jason W Locasale, Marcus W Bosenberg, Jeffrey C Rathmell, Susan M Kaech
Activated T cells engage aerobic glycolysis and anabolic metabolism for growth, proliferation, and effector functions. We propose that a glucose-poor tumor microenvironment limits aerobic glycolysis in tumor-infiltrating T cells, which suppresses tumoricidal effector functions. We discovered a new role for the glycolytic metabolite phosphoenolpyruvate (PEP) in sustaining T cell receptor-mediated Ca(2+)-NFAT signaling and effector functions by repressing sarco/ER Ca(2+)-ATPase (SERCA) activity. Tumor-specific CD4 and CD8 T cells could be metabolically reprogrammed by increasing PEP production through overexpression of phosphoenolpyruvate carboxykinase 1 (PCK1), which bolstered effector functions...
September 10, 2015: Cell
https://www.readbyqxmd.com/read/26316240/bone-health-and-osteoporosis
#16
REVIEW
Beatrice C Lupsa, Karl Insogna
Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age...
September 2015: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/26267443/dietary-protein-and-vitamin-d-intake-and-risk-of-falls-a-secondary-analysis-of-postmenopausal-women-from-the-study-of-osteoporotic-fractures
#17
Sarah C Larocque, Jane E Kerstetter, Jane A Cauley, Karl L Insogna, Kristine Ensrud, Li-Yung Lui, Heather G Allore
More than 90% of hip fractures in older Americans result from a fall. Inadequate intake of dietary protein and vitamin D are common in older adults, and diets in low these could contribute to loss of muscle mass and strength or coordination, in turn increasing the risk of falling. The objective of the study was to evaluate the relationship between protein and vitamin D intake with the occurrence of falls in older women in the Study of Osteoporotic Fracture, a prospective cohort of more than 4000 postmenopausal women participating from January 1997 to September 1998...
2015: Journal of Nutrition in Gerontology and Geriatrics
https://www.readbyqxmd.com/read/26176801/conventional-therapy-in-adults-with-x-linked-hypophosphatemia-effects-on-enthesopathy-and-dental-disease
#18
Jessica Connor, Elizabeth A Olear, Karl L Insogna, Lee Katz, Suher Baker, Raghbir Kaur, Christine A Simpson, John Sterpka, Robert Dubrow, Jane H Zhang, Thomas O Carpenter
CONTEXT: Treatment of X-linked hypophosphatemia (XLH) with active vitamin D metabolites and phosphate can partially correct skeletal deformities. It is unclear whether therapy influences the occurrence of two major long-term morbidities in XLH: enthesopathy and dental disease. OBJECTIVE: The objective of the study was to investigate the relationship between treatment and enthesopathy and dental disease in adult XLH patients. DESIGN: The study was designed as observational and cross-sectional...
October 2015: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26073451/pharmacokinetics-and-pharmacodynamics-of-a-human-monoclonal-anti-fgf23-antibody-krn23-in-the-first-multiple-ascending-dose-trial-treating-adults-with-x-linked-hypophosphatemia
#19
Xiaoping Zhang, Erik A Imel, Mary D Ruppe, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Thomas O Carpenter, Munro Peacock
In X-linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2 D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH...
February 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/25919461/prolonged-correction-of-serum-phosphorus-in-adults-with-x-linked-hypophosphatemia-using-monthly-doses-of-krn23
#20
MULTICENTER STUDY
Erik A Imel, Xiaoping Zhang, Mary D Ruppe, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
CONTEXT: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. OBJECTIVE: The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. DESIGN: Two sequential open-label phase 1/2 studies were done...
July 2015: Journal of Clinical Endocrinology and Metabolism
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