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Bone Reports

Megan M Pendleton, Saghi Sadoughi, Alfred Li, Grace D O'Connell, Joshua S Alwood, Tony M Keaveny
One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens...
December 2018: Bone Reports
Isabel D Colón-Bernal, Le T Duong, Brenda Pennypacker, James Henderson, Kenneth M Kozloff, Mark M Banaszak Holl
Anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. Once significant bone loss has occurred, the ability to restore biomechanical function may differ based on the drug chosen. To assess this question, bisphosphonate (alendronate, ALN) and cathepsin K inhibitor (MK-0674, CatKi) were employed in treatment mode to compare the relative changes to cancellous bone microstructure and mechanical properties in ovariectomized (OVX) cynomolgus monkeys. Lumbar vertebrae (LV) bone mineral density (BMD) values taken two years post-surgery prior to drug treatment show a 10-15% decrease (p < 0...
December 2018: Bone Reports
Kathleen Ang, Elizabeth Sanchez Rangel, Qianying Yuan, Dianqing Wu, Thomas O Carpenter, Karl Insogna
Context: Most heritable causes of low bone mass in children occur due to mutations affecting type 1 collagen. We describe two related patients with low bone mass and fracture without mutations in the type 1 collagen genes. Case description: We describe the index case of a 10-year-old girl with low-impact fractures in childhood and her 59-year-old father with traumatic fractures in adulthood, both with low bone mineral density. They were found to have the same heterozygous missense mutation in the WNT1 gene (p...
December 2018: Bone Reports
A Sean Alemi, Courtney M Mazur, Tristan W Fowler, Jonathon J Woo, P Daniel Knott, Tamara Alliston
Osteocytes support dynamic, cell-intrinsic resorption and deposition of bone matrix through a process called perilacunar/canalicular remodeling (PLR). In long bones, PLR depends on MMP13 and is tightly regulated by PTH, sclerostin, TGFβ, and glucocorticoids. However, PLR is regulated differently in the cochlea, suggesting a mechanism that is anatomically distinct. Unlike long bones, the mandible derives from neural crest and exhibits unique susceptibility to medication and radiation induced osteonecrosis. Therefore, we sought to determine if PLR in the mandible is suppressed by glucocorticoids, as it is in long bone...
December 2018: Bone Reports
Liping Xiao, Yurong Fei, Marja M Hurley
The mechanisms of the anabolic effect of parathyroid hormone (PTH) in bone are not fully defined. The bone anabolic effects of PTH require fibroblast growth factor 2 (FGF2) as well as Wnt signaling and FGF2 modulates Wnt signaling in osteoblasts. In vivo PTH administration differentially modulated Wnt signaling in bones of wild type (WT) and in mice that Fgf2 was knocked out ( Fgf2KO ). PTH increased Wnt10b mRNA and protein in WT but not in KO mice. Wnt antagonist SOST mRNA and protein was significantly higher in KO group...
December 2018: Bone Reports
Adolfredo Santana, Jeanne M Franzone, Cristina M McGreal, Richard W Kruse, Michael B Bober
Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2 . Recent investigations have discovered several other autosomal recessive genes responsible for OI. Among these genes is LEPRE1 , which is involved in post-translational modifications of collagen. To date, more than 40 LEPRE1 mutations have been described. One of these mutations is carried by 1.5% of West Africans and 0...
December 2018: Bone Reports
Antonia Ciani, Hechmi Toumi, Stéphane Pallu, Esther H R Tsai, Ana Diaz, Manuel Guizar-Sicairos, Mirko Holler, Eric Lespessailles, Cameron M Kewish
Ptychographic X-ray computed tomography (PXCT) is a quantitative imaging modality that non-destructively maps the 3D electron density inside an object with tens of nanometers spatial resolution. This method provides unique access to the morphology and structure of the osteocyte lacuno-canalicular network (LCN) and nanoscale density of the tissue in the vicinity of an osteocyte lacuna. Herein, we applied PXCT to characterize the lacunae and LCN in a male Wistar rat model of glucocorticoid-induced osteoporosis (GIO)...
December 2018: Bone Reports
Julius Simoni Leere, Christian Kruse, Maciej Robaczyk, Jesper Karmisholt, Peter Vestergaard
Purpose: Trabecular Bone Score (TBS) is a software-based method for indirect assessment of trabecular bone structure of the spine, based on analysis of pixels in dual energy x-ray absorptiometry (DXA) images. Few studies describe the use of TBS in patients with primary hyperparathyroidism (PHPT). This study aimed at further describing this relationship, investigating possible correlations between biochemistry, body mass index (BMI), fracture incidence and TBS. Methods: Cross-sectional study of 195 patients with verified PHPT, surgically (27) or conservatively (168) treated at the Department of Endocrinology, Aalborg University Hospital...
December 2018: Bone Reports
Sarah M Zimmerman, Melissa E Heard-Lipsmeyer, Milena Dimori, Jeff D Thostenson, Erin M Mannen, Charles A O'Brien, Roy Morello
Osteogenesis imperfecta (OI) is characterized by osteopenia and bone fragility, and OI patients during growth often exhibit high bone turnover with the net result of low bone mass. Recent evidence shows that osteocytes significantly affect bone remodeling under physiological and pathological conditions through production of osteoclastogenic cytokines. The receptor activator of nuclear factor kappa-B ligand (RANKL) produced by osteocytes for example, is a critical mediator of bone loss caused by ovariectomy, low-calcium diet, unloading and glucocorticoid treatment...
December 2018: Bone Reports
Kenneth A Philbrick, Carmen P Wong, Arianna M Kahler-Quesada, Dawn A Olson, Adam J Branscum, Russell T Turner, Urszula T Iwaniec
Focal bone resorption (osteolysis) induced by wear particles contributes to long-term orthopedic joint failure. However, the impact of focal osteolysis on remote skeletal sites has received less attention. The goal of this study was to determine the effects of polyethylene particles placed over calvaria on representative axial and appendicular skeletal sites in female mice. Because recent work has identified housing temperature as an important biological variable in mice, response to particle treatment was measured in animals housed at room (22 °C) and thermoneutral (32 °C) temperature...
December 2018: Bone Reports
Hiroaki Tanaka, Takenori Yamashita, Misao Yoneda, Satoshi Takagi, Toshihiro Miura
Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, hyperinsulinemia, and complications such as obesity and osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be investigated. The objective of the present study was to investigate the effects of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice. Methods: We determined the following parameters in TSOD mice and Tsumura, Suzuki, Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin levels; bone mass; bone microstructure; bone metabolic markers; and bone strength...
December 2018: Bone Reports
Thomas Lind, Roberta Lugano, Ann-Marie Gustafson, Maria Norgård, Arie van Haeringen, Anna Dimberg, Håkan Melhus, Stephen P Robertson, Göran Andersson
Angulated femurs are present prenatally both in CYP26B1 deficient humans with a reduced capacity to degrade retinoic acid (RA, the active metabolite of vitamin A), and mice overexpressing vascular endothelial growth factor a (Vegfa). Since excessive ingestion of vitamin A is known to induce spontaneous fractures and as the Vegfa-induced femur angulation in mice appears to be caused by intrauterine fractures, we analyzed bones from a CYP26B1 deficient human and rats with hypervitaminosis A to further explore Vegfa as a mechanistic link for the effect of vitamin A on bone...
December 2018: Bone Reports
Stacy A Semevolos, Katja F Duesterdieck-Zellmer, Maureen Larson, Marc A Kinsley
Osteochondrosis (OC) is a naturally occurring disease of the articular-epiphyseal cartilage and subchondral bone layers, leading to pain and decreased mobility. The objective of this study was to characterize gene and protein expression of apoptotic markers in chondrocytes surrounding cartilage canals and along the osteochondral junction of osteochondrosis (OC)-affected and normal cartilage, using naturally occurring disease in horses. Paraffin-embedded osteochondral samples (6 OC, 8 normal controls) and cDNA from chondrocytes captured with laser capture microdissection (4 OC, 6 normal controls) were obtained from the lateral trochlear ridge of femoropatellar joints in 14 immature horses (1-6 months of age)...
December 2018: Bone Reports
Kristen B Farrell, Alexander Karpeisky, Douglas H Thamm, Shawn Zinnen
Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types...
December 2018: Bone Reports
Takahiro Yamashita, Hiroshi Hagino, Ikuta Hayashi, Masako Hayashibara, Atsushi Tanida, Keita Nagira, Ryohei Fukui, Hideki Nagashima
Objectives: Cathepsin K is expressed by osteoclasts and synovial fibroblasts and degrades key components of bone and cartilage. Inhibition of cathepsin K protease activity may be beneficial for the prevention of bone erosion and cartilage degradation in rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) rat model is well established for studying the pathology and treatment of RA. We investigated the effect of ONO-KK1-300-01, a cathepsin K inhibitor (CKI), on arthritis and bone mineral density (BMD) in rats with CIA...
December 2018: Bone Reports
Takeshi Miyamoto, Akiyoshi Hirayama, Yuiko Sato, Tami Koboyashi, Eri Katsuyama, Hiroya Kanagawa, Atsuhiro Fujie, Mayu Morita, Ryuichi Watanabe, Toshimi Tando, Kana Miyamoto, Takashi Tsuji, Atsushi Funayama, Tomoyoshi Soga, Masaru Tomita, Masaya Nakamura, Morio Matsumoto
Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis...
December 2018: Bone Reports
Daniel D Bikle, Sophie Patzek, Yongmei Wang
Although the kidney was initially thought to be the sole organ responsible for the production of 1,25(OH)2 D via the enzyme CYP27b1, it is now appreciated that the expression of CYP27b1 in tissues other than the kidney is wide spread. However, the kidney is the major source for circulating 1,25(OH)2 D. Only in certain granulomatous diseases such as sarcoidosis does the extra renal tissue produce sufficient 1,25(OH)2 D to contribute to the circulating levels, generally associated with hypercalcemia, as illustrated by the case report preceding the review...
June 2018: Bone Reports
Megan E Mancuso, Joshua E Johnson, Sabahat S Ahmed, Tiffiny A Butler, Karen L Troy
While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk...
June 2018: Bone Reports
Jenny E Gunton, Christian M Girgis
Vitamin D is increasingly recognised to play an important role in normal muscle function. Low vitamin D status is associated with an increased risk of falls and proximal weakness. Since vitamin D deficiency is very common, and the signs are non-specific, it is important to maintain a high index of suspicion of vitamin D deficiency in patients with muscle pain and weakness, and it is simple to measure serum 25(OH) vitamin D. Therapy is cheap, safe and effective, but sometimes a larger dose may be needed, and, as shown in our case report, willingness of people to pay for an over the counter medication can be an issue...
June 2018: Bone Reports
Mikkel Bo Brent, Jesper Skovhus Thomsen, Annemarie Brüel
Thrombin is a key component in the coagulation cascade where it converts factor V, VIII, XI, and fibrinogen. In addition to the abundant production of thrombin in the liver, osteoclasts synthesize and secrete thrombin as well. Osteoblasts express thrombin receptors, and it has been reported that thrombin stimulates the expression of RANKL relatively to OPG, resulting in greater osteoclast activation and bone degradation. Pradaxa (dabigatran etexilate, DE) is a new anticoagulant, which has recently been approved for clinical use...
June 2018: Bone Reports
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