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Vertebral Bone Remodeling

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https://www.readbyqxmd.com/read/29180199/dose-dependent-effect-of-parathyroid-hormone-on-fracture-healing-and-bone-formation-in-mice
#1
Alexander Milstrey, Britta Wieskoetter, Daniel Hinze, Niklas Grueneweller, Richard Stange, Thomas Pap, Michael Raschke, Patric Garcia
BACKGROUND: Parathyroid hormone (PTH) is the only clinically approved osteoanabolic drug for osteoporosis treatment. However, PTH is not established for the treatment of fracture healing, and doses of PTH diverge significantly between different studies. We hypothesized that the effect of PTH on promoting fracture healing and bone formation is dose dependent. MATERIALS AND METHODS: In vivo, mice were treated with PTH (10, 40, and 200 μg/kg) in a closed femoral fracture model...
December 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29103161/multiple-vertebral-osteonecroses-k%C3%A3-mmell-s-disease-after-10%C3%A2-years-on-denosumab-is-osteocyte-apoptosis-to-blame
#2
Yves Maugars, Géraldine Bart, Pascale Guillot, Marguerite Chemel-Mary, Joëlle Glémarec, Mélanie Gahier-Penhoat, Benoit Le Goff, Christelle Darrieutort-Laffite
We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell's disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways...
November 4, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29044725/serum-sclerostin-levels-in-adults-with-osteogenesis-imperfecta-comparison-with-normal-individuals-and-response-to-teriparatide-therapy
#3
Lindsey Nicol, Ying Wang, Rosamund Smith, John Sloan, Sandesh C S Nagamani, Jay Shapiro, Brendan Lee, Eric Orwoll
Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an important regulator of bone remodeling. Osteogenesis imperfecta ([1]) is a heritable disorder of bone characterized by low bone mass, bone fragility, recurrent fractures, and bone deformities. Altered SOST-mediated signaling may have a role in pathogenesis of type I collagen-related OI; however this has not been evaluated in humans. We measured serum SOST levels in adults with OI who were enrolled in a randomized, placebo-controlled clinical trial that evaluated the effects of osteoanabolic therapy with teriparatide...
October 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/29017495/treatment-of-thoracic-or-lumbar-burst-fractures-with-balloon-assisted-endplate-reduction-using-tricalcium-phosphate-cement-histological-and-radiological-evaluation
#4
Joep Kitzen, Martijn G M Schotanus, Herbert S W Plasschaert, Frans-Jan H Hulsmans, Pieter B J Tilman
BACKGROUND: Short-segment pedicle-screw instrumentation is frequently used to stabilize thoracolumbar burst fractures. A recognized disadvantage of this procedure is recurrent kyphosis from intervertebral disc creep into the fractured central endplate. Balloon Assisted Endplate Reduction (BAER) using Tricalcium Phosphate bone cement (TCP) enables elevation of the centrally depressed endplate. Our objective was to evaluate the bone-tissue response to TCP and to analyse whether BAER using TCP can prevent recurrent kyphosis after removal of the instrumentation...
October 10, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28883093/role-of-the-ecm-in-notochord-formation-function-and-disease
#5
REVIEW
Valeria Trapani, Paolo Bonaldo, Diana Corallo
The notochord is a midline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function...
October 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28821457/spontaneous-mutation-of-dock7-results-in-lower-trabecular-bone-mass-and-impaired-periosteal-expansion-in-aged-female-misty-mice
#6
Phuong T Le, Kathleen A Bishop, David E Maridas, Katherine J Motyl, Daniel J Brooks, Kenichi Nagano, Roland Baron, Mary L Bouxsein, Clifford J Rosen
Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. While the low bone mineral density phenotype is in part due to higher sympathetic nervous system (SNS) drive in young mice, it is unclear what effect aging would have in mice homozygous for the mutation in the Dock7 gene...
December 2017: Bone
https://www.readbyqxmd.com/read/28796721/mechanisms-predisposing-factors-and-prognosis-of-intraoperative-vertebral-subluxation-during-pedicle-subtraction-osteotomy-in-surgical-correction-of-thoracolumbar-kyphosis-secondary-to-ankylosing-spondylitis
#7
Bang-Ping Qian, Sai-Hu Mao, Jun Jiang, Bin Wang, Yong Qiu
STUDY DESIGN: A retrospective study. OBJECTIVE: To analyze the mechanisms, predisposing factors, and prognosis of the intraoperative vertebral subluxation (VS) during pedicle subtraction osteotomy (PSO) for thoracolumbar kyphosis secondary to ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: VS is one of the most daunting challenges that surgeons encounter during PSO closure, especially in patients with AS with ankylosed and mostly osteoporotic spine...
August 15, 2017: Spine
https://www.readbyqxmd.com/read/28727345/-denosumab-in-clinical-practice-beware-before-during-and-after
#8
Olivier Lamy, Elena Gonzalez-Rodriguez, Delphine Stoll, Bérengère Aubry-Rozier
Denosumab is a very effective treatment of osteoporosis, easy to use and very well tolerated. Due to some associated risks, a close clinical follow-up is necessary. Before the first injection, it is necessary to correct hypocalcaemia or vitamin D deficiency when present. Calcemia has to be followed in case of renal insufficiency. Injections of denosumab should be done scrupulously every 6 months (± 3 weeks). Discontinuation of denosumab is associated with a severe rebound effect characterized by increased markers of bone remodeling, a rapid decrease of bone density values, and a risk of multiple spontaneous vertebral fractures...
April 19, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28631442/osteoblast-migration-in-vertebrate-bone
#9
Antonia Thiel, Marie K Reumann, Adele Boskey, Johannes Wischmann, Rüdiger von Eisenhart-Rothe, Philipp Mayer-Kuckuk
Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration...
June 19, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28591104/myeloma-bone-disease-pathogenesis-and-treatment
#10
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Bone involvement manifesting as osteolytic bone disease (OBD) or osteopenia is one of the defining features of multiple myeloma (MM). Osteolytic lesions develop in nearly 90% of patients with MM, and these are frequently complicated by skeleton-related events (SREs) such as severe bone pain, pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord compression. SREs have a negative effect on patients' quality of life and affect their long-term outcomes, including survival. In MM, the delicate balance between bone formation and bone destruction is perturbed...
April 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28585249/closure-of-the-vertebral-canal-in-human-embryos-and-fetuses
#11
Hayelom K Mekonen, Jill P J M Hikspoors, Greet Mommen, Nutmethee Kruepunga, S Eleonore Köhler, Wouter H Lamers
The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5-10 weeks of development) were visualized using Amira 3D(®) reconstruction and Cinema 4D(®) remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week...
June 5, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28458516/profile-of-romosozumab-and-its-potential-in-the-management-of-osteoporosis
#12
REVIEW
Sian Yik Lim, Marcy B Bolster
Increased understanding of bone biology has led to the discovery of several unique signaling pathways that regulate bone formation and resorption. The Wnt signaling pathway plays a significant role in skeletal development, adult skeletal homeostasis, and bone remodeling. Sclerostin is an inhibitor of the Wnt signaling pathway. Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28446689/bone-clarity-clearing-imaging-and-computational-analysis-of-osteoprogenitors-within-intact-bone-marrow
#13
Alon Greenbaum, Ken Y Chan, Tatyana Dobreva, David Brown, Deepak H Balani, Rogely Boyce, Henry M Kronenberg, Helen J McBride, Viviana Gradinaru
Bone tissue harbors unique and essential physiological processes, such as hematopoiesis, bone growth, and bone remodeling. To enable visualization of these processes at the cellular level in an intact environment, we developed "Bone CLARITY," a bone tissue clearing method. We used Bone CLARITY and a custom-built light-sheet fluorescence microscope to detect the endogenous fluorescence of Sox9-tdTomato(+) osteoprogenitor cells in the tibia, femur, and vertebral column of adult transgenic mice. To obtain a complete distribution map of these osteoprogenitor cells, we developed a computational pipeline that semiautomatically detects individual Sox9-tdTomato(+) cells in their native three-dimensional environment...
April 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28428078/kinetic-reconstruction-reveals-time-dependent-effects-of-romosozumab-on-bone-formation-and-osteoblast-function-in-vertebral-cancellous-and-cortical-bone-in-cynomolgus-monkeys
#14
Rogely Waite Boyce, Qing-Tian Niu, Michael S Ominsky
Romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption. The effects on bone formation are transient, eliciting a rapid increase in bone formation that attenuates with continued treatment. Although bone formation attenuates, bone mineral density (BMD) continues to increase. To explore potential tissue-level mechanisms that could contribute to a progressive increase in spine BMD, we used kinetic reconstruction techniques to examine the effects of romosozumab on modeling and remodeling units in vertebral cancellous bone from adult cynomolgus monkeys administered romosozumab for 10 and 28weeks...
April 18, 2017: Bone
https://www.readbyqxmd.com/read/28399348/prevalence-and-risk-factors-of-osteoporosisin-postmenopausal-women-with-type-2-diabetes-mellitus
#15
Ivan Raška, Mária Rašková, Vít Zikán, Jan Škrha
OBJECTIVE: Patients with type 2 diabetes (T2DM) are at increased risk of fractures. The aim of this study is to analyze the prevalence and risk factors of osteoporosis and osteoporosis related fractures in postmenopausal women with T2DM. METHODS: A total of 112 postmenopausal women with T2DM and 171 control nondiabetic women received a standardized questionnaire on osteoporosis risk factors, and were evaluated for bone mineral density (BMD, by using a dual energy X-ray absorptiometry), biochemical markers of bone and glucose metabolism, soluble receptor for advanced glycation end products (sRAGE) and its gene polymorphisms (rs1800625 or rs2070600)...
March 2017: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28389033/enamel-molecular-identity-of-its-transepithelial-ion-transport-system
#16
REVIEW
Rodrigo S Lacruz
Enamel is the most calcified tissue in vertebrates. It differs from bone in a number of characteristics including its origin from ectodermal epithelium, lack of remodeling capacity by the enamel forming cells, and absence of collagen. The enamel-forming cells known as ameloblasts, choreograph first the synthesis of a unique protein-rich matrix, followed by the mineralization of this matrix into a tissue that is ∼95% mineral. To do this, ameloblasts arrange the coordinated movement of ions across a cell barrier while removing matrix proteins and monitoring extracellular pH using a variety of buffering systems to enable the growth of carbonated apatite crystals...
July 2017: Cell Calcium
https://www.readbyqxmd.com/read/28366654/posterior-short-fusion-without-neural-decompression-using-pedicle-screws-and-spinous-process-plates-a-simple-and-effective-treatment-for-neurological-deficits-following-osteoporotic-vertebral-collapse
#17
Atsushi Nakano, Choman Ryu, Ichiro Baba, Takashi Fujishiro, Yoshiharu Nakaya, Masashi Neo
BACKGROUND: The optimal treatment of neurological deficits following osteoporotic vertebral collapse (OVC) is controversial, owing to complications that result from fragile bone quality. In the present study, we assessed surgical results following posterior spinal fusion without decompression. We achieved stable fusion over a short segment of the spinal column using pedicle screws and spinous process plates, maximizing the use of the preserved posterior elements. METHODS: We reviewed surgical data, perioperative complications, clinical outcomes, and radiographic data of 20 consecutively recruited patients with delayed neurological deficits following OVC, who experienced posterior short fusion without neural decompression...
March 30, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28303448/parathyroid-hormone-and-parathyroid-hormone-related-protein-analogs-in-osteoporosis-therapy
#18
REVIEW
Benjamin Z Leder
PURPOSE OF REVIEW: The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment. RECENT FINDINGS: The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone...
April 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28283537/increased-osteoclastogenesis-in-patients-with-vertebral-fractures-following-discontinuation-of-denosumab-treatment
#19
Athanasios D Anastasilakis, Maria P Yavropoulou, Polyzois Makras, Grigorios T Sakellariou, Fotini Papadopoulou, Spyridon Gerou, Socrates E Papapoulos
OBJECTIVE: To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment. DESIGN: In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5)...
June 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28254466/impaired-rib-bone-mass-and-quality-in-end-stage-cystic-fibrosis-patients
#20
Geneviève Mailhot, Natalie Dion, Delphine Farlay, Sébastien Rizzo, Nathalie J Bureau, Valérie Jomphe, Safiétou Sankhe, Georges Boivin, Larry C Lands, Pasquale Ferraro, Louis-Georges Ste-Marie
BACKGROUND: Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients...
May 2017: Bone
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