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Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research

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https://www.readbyqxmd.com/read/28337806/the-pharmacological-profile-of-a-novel-highly-potent-bisphosphonate-ox14-1-fluoro-2-imidazo-1-2-%C3%AE-pyridin-3-yl-ethyl-bisphosphonate
#1
M A Lawson, F H Ebetino, A Mazur, A D Chantry, J Paton-Hough, H R Evans, D Lath, M K Tsoumpra, M W Lundy, R L M Dobson, M Quijano, A A Kwaasi, J E Dunford, X Duan, J T Triffitt, G Jeans, R G G Russell
Bisphosphonates are widely used in the treatment of clinical disorders characterized by increased bone resorption, including osteoporosis, Paget's disease and the skeletal complications of malignancy. The anti-resorptive potency of the nitrogen-containing bisphosphonates on bone in vivo is now recognised to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates...
March 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28337794/muramyl-dipeptide-a-shared-structural-motif-of-peptidoglycans-is-a-novel-inducer-of-bone-formation-through-induction-of-runx2
#2
Ok-Jin Park, Jiseon Kim, Jihyun Yang, Cheol-Heui Yun, Seung Hyun Han
Peptidoglycan fragments released from gut microbiota can be delivered to the bone marrow and affect bone metabolism. Here, we investigated the regulation of bone metabolism by muramyl dipeptide (MDP), which is a shared structural unit of peptidoglycans. Increased bone and mineral density by enhanced bone formation were observed in mice administered with MDP. Remarkably, pre-treatment or post-treatment with MDP alleviated bone loss in RANKL-induced osteoporosis mouse models. MDP directly augmented osteoblast differentiation and bone-forming gene expression by Runx2 activation...
March 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28326606/physical-activity-sedentary-time-and-bone-strength-from-childhood-to-early-adulthood-a-mixed-longitudinal-hr-pqct-study
#3
Leigh Gabel, Heather M Macdonald, Lindsay Nettlefold, Heather A McKay
Bone strength is influenced by bone geometry, density, and bone microarchitecture, which adapt to increased mechanical loads during growth. Physical activity (PA) is essential for optimal bone strength accrual; however, less is known about how sedentary time influences bone strength and its determinants. Thus, our aim was to investigate the prospective associations between PA, sedentary time, and bone strength and its determinants during adolescence. We used HR-pQCT at distal tibia (8% site) and radius (7% site) in 173 girls and 136 boys (aged 9 to 20 years at baseline)...
March 22, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28322464/cathepsin-k-controls-cortical-bone-formation-by-degrading-periostin
#4
Nicolas Bonnet, Julia Brun, Jean-Charles Rousseau, Le T Duong, Serge L Ferrari
While inhibitors of bone resorption concomitantly reduce bone formation because of the coupling between osteoclasts and osteoblasts, inhibition or deletion of cathepsin k (CatK) stimulates bone formation despite decreasing resorption. The molecular mechanisms responsible for this increase in bone formation, particularly at periosteal surfaces where osteoclasts are relatively poor, remain unclear. Here we show that CatK pharmacological inhibition or deletion (Ctsk(-/-) mice) potentiates mechanotransduction signals mediating cortical bone formation...
March 21, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28316103/identification-of-hip-bmd-loss-and-fracture-risk-markers-through-population-based-serum-proteomics
#5
Carrie M Nielson, Jack Wiedrick, Jian Shen, Jon Jacobs, Erin S Baker, Aaron Baraff, Paul Piehowski, Christine G Lee, Arie Baratt, Vladislav Petyuk, Shannon McWeeney, Jeong Youn Lim, Douglas C Bauer, Nancy E Lane, Peggy M Cawthon, Richard D Smith, Jodi Lapidus, Eric S Orwoll
Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men Study (MrOS) comprises men ≥65 in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multi-dimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4...
March 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28304100/cartilage-specific-autophagy-deficiency-promotes-er-stress-and-impairs-chondrogenesis-in-perk-atf4-chop-dependent-manner
#6
Xiaomin Kang, Wei Yang, Dongxu Feng, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Tianping Xie, Huixia Li, Jiali Liu, Ruiqi Wang, Fang Li, Danhui Li, Hongzhi Sun, Shufang Wu
Autophagy is activated during nutritionally depleted or hypoxic conditions to facilitate cell survival. As growth plate is an avascular and hypoxic tissue, autophagy may have a crucial role during chondrogenesis, however the functional role and underlying mechanism of autophagy in regulation of growth plate remains elusive. In this study, we generated (TamCart) Atg7(-/-) (Atg7cKO) mice to explore the role of autophagy during endochondral ossification. Atg7cKO mice exhibited growth retardation associated with reduced chondrocyte proliferation, differentiation and increased chondrocyte apoptosis...
March 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28304097/improved-screening-test-for-idiopathic-infantile-hypercalcemia-confirms-residual-levels-of-serum-24-25-oh-2-d3-in-affected-patients
#7
Martin Kaufmann, Nicole Morse, Billy Joe Molloy, Donald P Cooper, Karl-Peter Schlingmann, Arnaud Molin, Marie Laure Kottler, J Christopher Gallagher, Laura Armas, Glenville Jones
BACKGROUND: CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid LC-MS/MS-based blood test enabling measurement of the 25-OH-D3 :24,25-(OH)2 D3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D3 by CYP24A1 in vivo. While values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH)2 D3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH)2 D3 peak on LC-MS/MS...
March 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28300346/association-of-trabecular-bone-score-tbs-with-incident-clinical-and-radiographic-vertebral-fractures-adjusted-for-lumbar-spine-bmd-in-older-men-a-prospective-cohort-study
#8
John T Schousboe, Tien N Vo, Lisa Langsetmo, Brent C Taylor, Peggy M Cawthon, Ann V Schwartz, Douglas C Bauer, Eric S Orwoll, Nancy E Lane, Elizabeth Barrett-Connor, Kristine E Ensrud
The association of Trabecular Bone Score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine DXA scans for 5,831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4,309 men with baseline and follow-up lateral spine radiographs (mean 4...
March 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28300329/insulin-resistance-and-the-igf-i-cortical-bone-relationship-in-children-ages-9-13-years
#9
Joseph M Kindler, Norman K Pollock, Emma M Laing, Assaf Oshri, Nathan T Jenkins, Carlos M Isales, Mark W Hamrick, Ke-Hong Ding, Dorothy B Hausman, George P McCabe, Berdine R Martin, Kathleen M Hill Gallant, Stuart J Warden, Connie M Weaver, Munro Peacock, Richard D Lewis
IGF-I is a pivotal hormone in pediatric musculoskeletal development. Though recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone...
March 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28300324/risk-of-stress-fracture-varies-by-race-ethnic-origin-in-a-cohort-study-of-1-3-million-u-s-army-soldiers
#10
Lakmini Bulathsinhala, Julie M Hughes, Craig J McKinnon, Joseph R Kardouni, Katelyn I Guerriere, Kristin L Popp, Ronald W Matheny, Mary L Bouxsein
Stress fractures (SF) are common and costly injuries in military personnel. Risk for SF has been shown to vary with race/ethnicity. Previous studies report increased SF risk in White and Hispanic Soldiers compared to Black soldiers. However, these studies did not account for the large ethnic diversity in the U.S. Military. PURPOSE: We aimed to identify differences in SF risk among racial/ethnic groups within the U.S. Army. METHODS: A retrospective cohort study was conducted using data from the Total Army Injury and Health Outcomes Database from 2001 until 2011...
March 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28300321/skeletal-colonization-by-breast-cancer-cells-is-stimulated-by-an-osteoblast-and-%C3%AE-2ar-dependent-neo-angiogenic-switch
#11
Patrick L Mulcrone, J Preston Campbell, Lise Clément-Demange, Ana Lia Anbinder, Alyssa R Merkel, Rolf A Brekken, Julie A Sterling, Florent Elefteriou
The skeleton is a common site for breast cancer metastasis. Although significant progress has been made to manage osteolytic bone lesions, the mechanisms driving the early steps of the bone metastatic process are still not sufficiently understood to design efficacious strategies needed to inhibit this process and offer preventative therapeutic options. Progression and recurrence of breast cancer, as well as reduced survival of patients with breast cancer, are associated with chronic stress, a condition known to stimulate sympathetic nerve outflow...
March 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28294415/the-estimation-of-second-generation-hr-pqct-from-first-generation-hr-pqct-using-in-vivo-cross-calibration
#12
Sarah L Manske, Erin M Davison, Lauren A Burt, Duncan A Raymond, Steven K Boyd
Second generation high resolution peripheral quantitative computed tomography (HR-pQCT) provides the highest resolution in vivo to assess bone density and microarchitecture in 3D. While strong agreement of most outcomes measured with first (XCTI) and second (XCTII) generation HR-pQCT has been demonstrated, the ability to use the two systems interchangeably is unknown. From in vivo measurements, we determined the limits of estimating XCTII data from XCTI scans conducted in vivo, and whether that estimation can be improved by linear cross-calibration equations...
March 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28294411/response-to-letter-to-the-editor-of-jbmr-treatment-sequence-matters
#13
LETTER
Felicia Cosman, Jeri W Nieves, David W Dempster
We thank Drs. Grey, Bolland and Cundy for their interest in our perspective entitled "Treatment Sequence matters: anabolic and antiresorptive therapy for osteoporosis"((1)) in which we support the concept that anabolic treatment should be considered first line for patients at high risk for fracture. Drs. Grey and colleagues argue that there is insufficient evidence to justify this recommendation. While we agree that randomized trials to confirm that anabolic therapies reduce hip fracture risk would be valuable, it is likely that we will never have such evidence; absence of this evidence does not mean that the medications are not effective...
March 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28294409/maintaining-order-in-osteoporosis-treatments
#14
LETTER
Andrew Grey, Mark Bolland, Tim Cundy
Cosman et al recommend a major change in clinical practice, the initiation of therapy for osteoporosis with an anabolic agent, followed sequentially by an anti-resorptive agent.(1) We do not think the available evidence justifies such advice. First, it is based on trials of short duration with surrogate endpoints for fracture, such as bone mineral density and bone turnover. This article is protected by copyright. All rights reserved.
March 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28294405/cross-sectional-versus-longitudinal-change-in-a-prospective-hr-pqct-study
#15
Lauren A Burt, David A Hanley, Steven K Boyd
Longitudinal studies assessing age-related changes using high-resolution peripheral quantitative computed tomography (HR-pQCT) provide novel insight compared with cross-sectional analyses. The purpose of this cohort study was 1) to determine individuals' change in HR-pQCT parameters over five years relative to least significant change (LSC), and 2) to evaluate if predicted rate of change from cross-sectional data is comparable to actual change from longitudinal investigation. A cohort of 466 (162 male; 304 female) participants completed two HR-pQCT scans with five years between assessments...
March 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28277610/the-notch-ligand-jagged1-regulates-the-osteoblastic-lineage-by-maintaining-the-osteoprogenitor-pool
#16
Rialnat A Lawal, Xichao Zhou, Kaylind Batey, Corey M Hoffman, Mary A Georger, Freddy Radtke, Matthew J Hilton, Lianping Xing, Benjamin J Frisch, Laura M Calvi
Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged1 contributes to bone homeostasis, selective deletion of Jagged1 in osteolineage cells was achieved through the presence of Prx1 promoter-driven Cre recombinase expression, targeting mesenchymal stem cells (MSCs) and their progeny (PJag1 mice). PJag1 mice were viable and fertile and did not exhibit any skeletal abnormalities at 2 weeks of age...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28277603/safety-observations-with-three-years-of-denosumab-exposure-comparison-between-subjects-who-received-denosumab-during-the-randomized-freedom-trial-and-subjects-who-crossed-over-to-denosumab-during-the-freedom-extension
#17
N B Watts, J P Brown, S Papapoulos, E M Lewiecki, D L Kendler, P Dakin, R B Wagman, A Wang, N S Daizadeh, S Smith, H G Bone
Denosumab is a fully human monoclonal antibody against RANKL that decreases osteoclast formation, function and survival, and is approved for the treatment of postmenopausal women with osteoporosis at increased or high risk for fracture, among other indications. During the pivotal 3-year fracture trial FREEDOM, denosumab 60 mg subcutaneously every 6 months significantly reduced new vertebral (68%), hip (40%), and nonvertebral (20%) fractures; increased bone mineral density (BMD); and reduced bone turnover markers compared with placebo in postmenopausal women with osteoporosis...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28276598/clinical-utility-of-using-lumbar-spine-trabecular-bone-score-to-adjust-fracture-probability-the-manitoba-bmd-cohort
#18
P Martineau, W D Leslie, H Johansson, A Oden, E V McCloskey, D Hans, J A Kanis
Decreased lumbar spine trabecular bone score (TBS), a DXA-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of ten-year fracture probability estimated using FRAX(R) . We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28276596/impact-of-calcium-and-two-doses-of-vitamin-d-on-bone-metabolism-in-the-elderly-a-randomized-controlled-trial
#19
Maya Rahme, Sima-Lynn Sharara, Rafic Baddoura, Robert H Habib, Georges Halaby, Asma Arabi, Ravinder J Singh, Moustapha Kassem, Ziyad Mahfoud, Maha Hoteit, Rose T Daher, Darina Bassil, Karim El Ferkh, Ghada El-Hajj Fuleihan
The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis a vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3,750IU/day or 600 IU/day of vitamin D3 for one year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m(2) , 55% were women, and 222 completed the 12-months follow-up...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28276592/low-serum-dheas-predicts-increased-fracture-risk-in-older-men-the-mros-sweden-study
#20
Claes Ohlsson, Maria Nethander, Andreas Kindmark, Östen Ljunggren, Mattias Lorentzon, Björn E Rosengren, Magnus K Karlsson, Dan Mellström, Liesbeth Vandenput
The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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