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Osteoporosis

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82 papers 0 to 25 followers
https://www.readbyqxmd.com/read/28193701/osteoblastic-lrp4-promotes-osteoclastogenesis-by-regulating-atp-release-and-adenosine-a2ar-signaling
#1
Lei Xiong, Ji-Ung Jung, Hao-Han Guo, Jin-Xiu Pan, Xiang-Dong Sun, Lin Mei, Wen-Cheng Xiong
Bone homeostasis depends on the functional balance of osteoblasts (OBs) and osteoclasts (OCs). Lrp4 is a transmembrane protein that is mutated in patients with high bone mass. Loss of Lrp4 in OB-lineage cells increases bone mass by elevating bone formation by OBs and reducing bone resorption by OCs. However, it is unclear how Lrp4 deficiency in OBs impairs osteoclastogenesis. Here, we provide evidence that loss of Lrp4 in the OB lineage stabilizes the prorenin receptor (PRR) and increases PRR/V-ATPase-driven ATP release, thereby enhancing the production of the ATP derivative adenosine...
February 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28144701/observations-following-discontinuation-of-long-term-denosumab-therapy
#2
M R McClung, R B Wagman, P D Miller, A Wang, E M Lewiecki
: Stopping denosumab after 8 years of continued treatment was associated with bone loss during a 1-year observation study in patients who were not prescribed osteoporosis treatment. Bone loss was attenuated in patients who began another osteoporosis therapy. Treatment to prevent bone loss upon stopping denosumab should be considered. INTRODUCTION: This study aimed to understand osteoporosis management strategies during a 1-year observational follow-up after up to 8 years of denosumab treatment in a phase 2 study...
January 31, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/26348019/mutations-in-known-monogenic-high-bone-mass-loci-only-explain-a-small-proportion-of-high-bone-mass-cases
#3
Celia L Gregson, Lawrie Wheeler, Sarah A Hardcastle, Louise H Appleton, Kathryn A Addison, Marieke Brugmans, Graeme R Clark, Kate A Ward, Margaret Paggiosi, Mike Stone, Joegi Thomas, Rohan Agarwal, Kenneth E S Poole, Eugene McCloskey, William D Fraser, Eleanor Williams, Alex N Bullock, George Davey Smith, Matthew A Brown, Jon H Tobias, Emma L Duncan
High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3')...
March 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27742500/sclerostin-deficiency-in-humans
#4
Antoon H van Lierop, Natasha M Appelman-Dijkstra, Socrates E Papapoulos
Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasias caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis...
October 11, 2016: Bone
https://www.readbyqxmd.com/read/28079119/interleukin-32-gamma-stimulates-bone-formation-by-increasing-mir-29a-in-osteoblastic-cells-and-prevents-the-development-of-osteoporosis
#5
Eun-Jin Lee, Sang-Min Kim, Bongkun Choi, Eun-Young Kim, Yeon-Ho Chung, Eun-Ju Lee, Bin Yoo, Chang-Keun Lee, Seokchan Hong, Beom-Jun Kim, Jung-Min Koh, Soo-Hyun Kim, Yong-Gil Kim, Eun-Ju Chang
Interleukin-32 gamma (IL-32γ) is a recently discovered cytokine that is elevated in inflamed tissues and contributes to pathogenic features of bone in human inflammatory rheumatic diseases. Nevertheless, the role of IL-32γ and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32γ in bone remodeling and the hypothetical correlation between IL-32γ and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32γ showed reduced bone loss with advancing age, increased bone formation, and high osteogenic capacity of osteoblast compared to wild-type (WT) mice through the upregulation of miR-29a, which caused a reduction of Dickkopf-1 (DKK1) expression...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/23074140/van-buchem-disease-clinical-biochemical-and-densitometric-features-of-patients-and-disease-carriers
#6
Antoon H van Lierop, Neveen A T Hamdy, Martje E van Egmond, Egbert Bakker, Freek G Dikkers, Socrates E Papapoulos
Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte-derived negative regulator of bone formation. We studied the demographic, clinical, biochemical, and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%); raised intracranial pressure had been documented in 20%...
April 2013: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27980413/high-bone-turnover-elevates-the-risk-of-denosumab-induced-hypocalcemia-in-women-with-postmenopausal-osteoporosis
#7
Koji Ishikawa, Takashi Nagai, Keizo Sakamoto, Kenji Ohara, Takeshi Eguro, Hiroshi Ito, Yoichi Toyoshima, Akatsuki Kokaze, Tomoaki Toyone, Katsunori Inagaki
Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX)...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27888287/wnt-signaling-and-cellular-metabolism-in-osteoblasts
#8
REVIEW
Courtney M Karner, Fanxin Long
The adult human skeleton is a multifunctional organ undergoing continuous remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite balance between bone resorption by osteoclasts and bone formation by osteoblasts; disturbance of such balance is the root cause for various bone disorders including osteoporosis. To develop effective and safe therapeutics to modulate bone formation, it is essential to elucidate the molecular mechanisms governing osteoblast differentiation and activity. Due to their specialized function in collagen synthesis and secretion, osteoblasts are expected to consume large amounts of nutrients...
November 26, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27742498/role-and-mechanism-of-action-of-sclerostin-in-bone
#9
Jesus Delgado-Calle, Amy Y Sato, Teresita Bellido
After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass, as well as the damaging effects of some cancers in bone...
October 12, 2016: Bone
https://www.readbyqxmd.com/read/27811938/bone-romosozumab-getting-there-but-not-quite-yet
#10
Socrates E Papapoulos
No abstract text is available yet for this article.
November 4, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27746742/molecular-mechanisms-of-obesity-induced-osteoporosis-and-muscle-atrophy
#11
Bipradas Roy, Mary E Curtis, Letimicia S Fears, Samuel N Nahashon, Hugh M Fentress
Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), macrophage colony stimulating factor (M-CSF), growth hormone (GH), parathyroid hormone (PTH), angiotensin II (Ang II), 5-hydroxy-tryptamine (5-HT), Advance glycation end products (AGE), and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27776363/calcium-intake-and-cardiovascular-disease-risk-an-updated-systematic-review-and-meta-analysis
#12
Mei Chung, Alice M Tang, Zhuxuan Fu, Ding Ding Wang, Sydne Jennifer Newberry
Background: Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake. Purpose: To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults. Data Sources: MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016...
December 20, 2016: Annals of Internal Medicine
https://www.readbyqxmd.com/read/27781192/staged-correction-of-severe-thoracic-kyphosis-in-patients-with-multilevel-osteoporotic-vertebral-compression-fractures
#13
Eyal Behrbalk, Ofir Uri, Yoram Folman, Marcus Rickert, Radek Kaiser, Bronek Maximilian Boszczyk
Study Design Technical report. Objective Multilevel osteoporotic vertebral compression fractures may lead to considerable thoracic deformity and sagittal imbalance, which may necessitate surgical intervention. Correction of advanced thoracic kyphosis in patients with severe osteoporosis remains challenging, with a high rate of failure. This study describes a surgical technique of staged vertebral augmentation with osteotomies for the treatment of advanced thoracic kyphosis in patients with osteoporotic multilevel vertebral compression fractures...
November 2016: Global Spine Journal
https://www.readbyqxmd.com/read/27759931/managing-osteoporosis-in-patients-on-long-term-bisphosphonate-treatment-report-of-a-task-force-of-the-american-society-for-bone-and-mineral-research
#14
Robert A Adler, Ghada El-Hajj Fuleihan, Douglas C Bauer, Pauline M Camacho, Bart L Clarke, Gregory A Clines, Juliet E Compston, Matthew T Drake, Beatrice J Edwards, Murray J Favus, Susan L Greenspan, Ross McKinney, Robert J Pignolo, Deborah E Sellmeyer
No abstract text is available yet for this article.
October 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27732325/stress-fractures-concepts-and-therapeutics
#15
Carolina A Moreira, John P Bilezikian
CONTEXT: Stress fractures are repetitive use injuries in which recurrent strains lead to material fatigue and microarchitectural discontinuities. Stress fractures account for up to 20% of athletic injuries, more commonly sustained by women and in those who engage in track-and-field events. The pathogenesis of stress fractures is multifactorial. Although most stress fracture are reported among women who may experience menstrual disturbances, low body mass index, low energy intake and sometimes low bone mass, these individuals do not regularly seek endocrinological attention...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27622692/effect-of-denosumab-on-peripheral-compartmental-bone-density-microarchitecture-and-estimated-bone-strength-in-de-novo-kidney-transplant-recipients
#16
Marco Bonani, Ursina Meyer, Diana Frey, Nicole Graf, Heike A Bischoff-Ferrari, Rudolf P Wüthrich
BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. METHODS: The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14)...
2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/27641359/building-better-bones-with-biologics-a-new-approach-to-osteoporosis
#17
EDITORIAL
Clifford J Rosen, Julie R Ingelfinger
No abstract text is available yet for this article.
October 20, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27641143/romosozumab-treatment-in-postmenopausal-women-with-osteoporosis
#18
RANDOMIZED CONTROLLED TRIAL
Felicia Cosman, Daria B Crittenden, Jonathan D Adachi, Neil Binkley, Edward Czerwinski, Serge Ferrari, Lorenz C Hofbauer, Edith Lau, E Michael Lewiecki, Akimitsu Miyauchi, Cristiano A F Zerbini, Cassandra E Milmont, Li Chen, Judy Maddox, Paul D Meisner, Cesar Libanati, Andreas Grauer
Background Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Methods We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months...
October 20, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27631671/reinvigorating-the-osteoporosis-message
#19
Michael R McClung
No abstract text is available yet for this article.
September 15, 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27559463/selective-estrogen-receptor-modulators
#20
REVIEW
Ki-Chan An
Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women...
August 2016: Asian Spine Journal
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