ISSN 1662-4009 (online)

ey0016.4-11 | New Mechanisms | ESPEYB16

4.11. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice

K Mao , GF Quipildor , T Tabrizian , A Novaj , F Guan , RO Walters , F Delahaye , GB Hubbard , Y Ikeno , K Ejima , P Li , DB Allison , H Salimi-Moosavi , PJ Beltran , P Cohen , N Barzilai , DM Huffman

To read the full abstract: Nat Commun. 2018 19;9:2394.“Somatopause” causes the physiological decline over time in GH secretion leading to low IGF-I levels in aging subjects. GH has been proposed as an anti-aging therapy, but with no evidence of beneficial effects and with some potential risks [1,2]. Therefore, current guidelines do not recommend GH therapy as anti-aging treatme...

ey0016.5-16 | Basic Science - Bone | ESPEYB16

5.16. Discovery of a periosteal stem cell mediating intramembranous bone formation

S Debnath , AR Yallowitz , J McCormick , S Lalani , T Zhang , R Xu , N Li , Y Liu , YS Yang , M Eiseman , JH Shim , M Hameed , JH Healey , MP Bostrom , DA Landau , MB Greenblatt

Abstract: Nature. 2018 Oct;562(7725):133–139.In brief: A newly discovered periosteal stem cell pool with features distinct from other skeletal mesenchymal stem cells (MSCs) is present in murine and human bone and reveals a pivotal function in intramembranous ossification, cortical bone architecture and fracture healing in conditional knockout mouse strains.</st...

ey0016.14-17 | (1) | ESPEYB16

14.17. Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia

S Bhattacharya , J Li , A Sockell , MJ Kan , FA Bava , SC Chen , MC Avila-Arcos , X Ji , E Smith , NB Asadi , RS Lachman , HYK Lam , CD Bustamante , AJ Butte , GP Nolan

To read the full abstract: Genome Res 2018;28:423–431The discovery of a mummified humanoid female skeleton on a shelf in a building in La Noria, Chile in 2003 created enormous scientific and popular interest. Its highly unusual appearance included a length of only 6 inches despite a bone age of 6–7 years old, marked turricephaly (a cone-shaped top of the skull), and reduced number...

ey0015.2-15 | Gestational weight gain above certain recommendations is associated with adverse outome for both child and mother | ESPEYB15

Gestational weight gain above certain recommendations is associated with adverse outome for both child and mother

RF Goldstein , SK Abell , S Ranasinha , M Misso , JA Boyle , MH Black , N Li , G Hu , F Corrado , L Rode , YJ Kim , M Haugen , WO Song , MH Kim , A Bogaerts , R Devlieger , JH Chung , HJ Teede

To read the full abstract: JAMA 2017 Jun 6;317(21):2207-2225Excessive and insufficient gestational weight gain are associated with adverse pregnancy outcomes, including small for gestational age (SGA), large for gestational age (LGA), macrosomia, cesarean delivery, gestational diabetes mellitus (GDM), preeclampsia, postpartum weight retention, and offspring obesity. The Institute of Medicine (IO...

ey0015.5-4 | New genes and gene mutations | ESPEYB15

5.4 Mutations That Alter the Carboxy-Terminal-Propeptide Cleavage Site of the Chains of Type I Procollagen Are Associated With a Unique Osteogenesis Imperfecta Phenotype

T Cundy , M Dray , J Delahunt , JD Hald , B Langdahl , C Li , M Szybowska , S Mohammed , EL Duncan , AM McInerney-Leo , PG Wheeler , P Roschger , K Klaushofer , J Rai , M Weis , D Eyre , U Schwarze , PH Byers

To read the full abstract: J Bone Miner Res 2018;33(7):1260-1271Osteogenesis imperfecta (OI) is characterized by early-onset skeletal fragility, often short stature, blue sclerae and some other features. OI is caused by mutations in the two genes encoding type I collagen, namely COL1A1 and COL1A2. Some previous reports have indicated that when the mutation involves the C-propeptide cleavage site in e...

ey0015.8-12 | Clinical Trials – New Treatments | ESPEYB15

8.12 Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

B Venkatesh , S Finfer , J Cohen , D Rajbhandari , Y Arabi , R Bellomo , L Billot , M Correa , P Glass , M Harward , C Joyce , Q Li , C McArthur , A Perner , A Rhodes , K Thompson , S Webb , J Myburgh

To read the full abstract: N Engl J Med. 2018; 378(9): 797-808Sepsis has been identified by the WHO as a global health priority, however, there has been no proven pharmacologic treatment other than the appropriate antibiotic agents, fluids and vasopressors as required. Reported death rates among hospitalized patients with sepsis range between 30-45% (22). Glucocorticoids have been used as ...

ey0015.14-17 | Who could have predicted it? | ESPEYB15

14.17 Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial

D Athauda , K Maclagan , SS Skene , M Bajwa-Joseph , D Letchford , K Chowdhury , S Hibbert , N Budnik , L Zampedri , J Dickson , Y Li , I Aviles-Olmos , TT Warner , P Limousin , AJ Lees , NH Greig , S Tebbs , T Foltynie

To read the full abstract: Lancet 2017;390:1664-1675Whoever could have imagined that a compound discovered as being secreted by enteroendocrine cells in the gut could have a role in treating Parkinson’s disease? GLP-1 does indeed have diverse actions on several peripheral organs (including tongue, stomach, adipose tissues, muscle, pancreas and liver) and on the brainstem to regulate...

ey0020.3-1 | Novel Treatments for Rare Skeletal Disorders | ESPEYB20

3.1. Safety and efficacy of denosumab for fibrous dysplasia of bone

LF de Castro , Z Michel , K Pan , J Taylor , V Szymczuk , S Paravastu , B Saboury , GZ Papadakis , X Li , K Milligan , B Boyce , SM Paul , MT Collins , AM Boyce

In Brief: This phase 2 study investigated the effect of the RANKL inhibitor denosumab on fibrous dysplasia lesion activity, as well as the rebound in bone turnover after treatment discontinuation.Commentary: Denosumab is a humanized monoclonal antibody that inhibits RANKL with potent but transient antiosteoclastic effects, and discontinuation of denosumab treatment is associated with a rebound in bone turnover. In this study, eight women received high do...

ey0020.3-14 | Advances in Growth, Bone Biology, and Mineral Metabolism | ESPEYB20

3.14. SIRT2 regulates extracellular vesicle-mediated liver-bone communication

L Lin , Z Guo , E He , X Long , D Wang , Y Zhang , W Guo , Q Wei , W He , W Wu , J Li , L Wo , D Hong , J Zheng , M He , Q Zhao

In Brief: These authors studied liver-specific SIRT2 knockout mice to examine how loss of hepatocyte SIRT2 (Sirtuin 2) prevents bone loss in aged mice. Hepatocyte SIRT2 deficiency led to upregulation of Leucine rich α2 glycoprotein (LRG1) in hepatocyte-derived small extracellular vesicles (sEVs) which inhibited osteoclastogenesis in bone marrow.Commentary: Liver-bone communication has been implicated in bone homeostasis. P...

ey0020.8-15 | New Hopes | ESPEYB20

8.15. Exocrine pancreas regeneration modifies original pancreas to alleviate diabetes in mouse models

X Kou , J Liu , D Wang , M Yu , C Li , L Lu , C Chen , D Liu , W Yu , T Yu , Y Liu , X Mao , A Naji , T Cai , L Sun , S Shi

Brief summary: In this experimental study, pancreas-derived mesenchymal stem cells (PMSCs) were implanted into the kidney capsule of mice with streptozotocin (STZ)-induced diabetes. PMSCs led to increased levels of IL-6 in T-helper 1 and T-helper 17 cells, which transiently activated tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), which in turn decreased levels of interleukin-17. This was associated with exocrine pancreas regeneration and rescue of ...