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Current Osteoporosis Reports

Creighton T Tuzon, Diana Rigueur, Amy E Merrill
PURPOSE OF REVIEW: Fibroblast growth factor receptor (FGFR) signaling regulates proliferation and differentiation during development and homeostasis. While membrane-bound FGFRs play a central role in these processes, the function of nuclear FGFRs is also critical. Here, we highlight mechanisms for nuclear FGFR translocation and the effects of nuclear FGFRs on skeletal development and disease. RECENT FINDINGS: Full-length FGFRs, internalized by endocytosis, enter the nucleus through β-importin-dependent mechanisms that recognize the nuclear localization signal within FGFs...
April 13, 2019: Current Osteoporosis Reports
Petar Milovanovic, Björn Busse
PURPOSE OF REVIEW: This article provides a review on the variability of the osteocyte lacunar network in the human skeleton. It highlights characteristics of the osteocyte lacunar network in relation to different skeletal sites and fracture susceptibility. RECENT FINDINGS: Application of 2D analyses (quantitative backscattered electron microscopy, histology, confocal laser scanning microscopy) and 3D reconstructions (microcomputed tomography and synchrotron radiation microcomputed tomography) provides extended high-resolution information on osteocyte lacunar properties in individuals of various age (fetal, children's growth, elderly), sex, and disease states with increased fracture risk...
April 12, 2019: Current Osteoporosis Reports
Lena Ingeborg Wolff, Christine Hartmann
PURPOSE OF REVIEW: The goal of the review is to summarize the current knowledge on the process of chondrocyte-to-osteoblast transdifferentiation during endochondral bone formation and its potential implications in fracture healing and disease. RECENT FINDINGS: Lineage tracing experiments confirmed the transdifferentiation of chondrocytes into osteoblasts. More recent studies lead to the discovery of molecules involved in this process, as well as to the hypothesis that these cells may re-enter a stem cell-like phase prior to their osteoblastic differentiation...
April 4, 2019: Current Osteoporosis Reports
Teun J de Vries, Carmen Huesa
PURPOSE OF REVIEW: Periodontitis is the inflammation-associated bone loss disease of the alveolar bone that surrounds teeth. Classically, the emphasis on the etiology of periodontitis has been on the products of periodontal pathogens that lead to an inflammatory response of the soft tissues of the periodontium, eventually leading to activation of osteoclasts that degrade the alveolar bone. Until recently, the response of osteocytes that populate the alveolar bone, and that are known for their regulatory role in bone anabolism and catabolism, has not been addressed...
March 28, 2019: Current Osteoporosis Reports
Nicklas Højgaard Rasmussen, Jakob Dal
PURPOSE OF REVIEW: Based on a systematic literature search, we performed a comprehensive review of risk factors for falls and fractures in patients with diabetes. RECENT FINDINGS: Patients with diabetes have an increased risk of fractures partly explained by increased bone fragility. Several risk factors as altered body composition including sarcopenia and obesity, impaired postural control, gait deficits, neuropathy, cardiovascular disease, and other co-morbidities are considered to increase the risk of falling...
March 26, 2019: Current Osteoporosis Reports
Miao Zhou, Shuyi Li, Janak L Pathak
PURPOSE OF REVIEW: An elevated level of pro-inflammatory cytokines in inflammatory conditions causes bone loss and disrupts vital organ function. Osteocytes comprise > 95% of the cellular component in bone tissue, produce a range of cytokines and signaling molecules, and influence bone and other organ function. In this review, we hypothesized that an elevated level of pro-inflammatory cytokines in inflammatory conditions affects osteocyte survival and function thereby possibly amplifying inflammation, and causing bone loss and non-bone clinical complications...
March 26, 2019: Current Osteoporosis Reports
Eric Hesse, Hanna Taipaleenmäki
PURPOSE OF REVIEW: This review provides an update on the recent literature describing the role of microRNAs (miRNAs) in cancer formation and bone metastasis. We confined our focus on osteosarcoma, breast cancer, prostate cancer, and epithelial-mesenchymal transition. RECENT FINDINGS: In all areas covered, major discoveries on the role of miRNAs in tumorigenesis and metastasis have been made. Novel signaling networks were identified with miRNAs having a central function...
March 23, 2019: Current Osteoporosis Reports
Judith M Hollander, Li Zeng
PURPOSE OF REVIEW: Proper cartilage development is critical to bone formation during endochondral ossification. This review highlights the current understanding of various aspects of glucose metabolism in chondrocytes during cartilage development. RECENT FINDINGS: Recent studies indicate that chondrocytes transdifferentiate into osteoblasts and bone marrow stromal cells during endochondral ossification. In cartilage development, signaling molecules, including IGF2 and BMP2, tightly control glucose uptake and utilization in a stage-specific manner...
March 4, 2019: Current Osteoporosis Reports
Katerina Trajanoska, Fernando Rivadeneira, Douglas P Kiel, David Karasik
PURPOSE OF REVIEW: To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. RECENT FINDINGS: Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1...
February 28, 2019: Current Osteoporosis Reports
Robert J Pignolo, Rebekah M Samsonraj, Susan F Law, Haitao Wang, Abhishek Chandra
PURPOSE OF REVIEW: We review cell senescence in the context of age-related bone loss by broadly discussing aging mechanisms in bone, currently known inducers and markers of senescence, the senescence-associated secretory phenotype (SASP), and the emerging roles of senescence in bone homeostasis and pathology. RECENT FINDINGS: Cellular senescence is a state of irreversible cell cycle arrest induced by insults or stressors including telomere attrition, oxidative stress, DNA damage, oncogene activation, and other intrinsic or extrinsic triggers and there is mounting evidence for the role of senescence in aging bone...
February 26, 2019: Current Osteoporosis Reports
Clare E Yellowley, Damian C Genetos
PURPOSE OF REVIEW: We reviewed recent literature on oxygen sensing in osteogenic cells and its contribution to development of a skeletal phenotype, the coupling of osteogenesis with angiogenesis and integration of hypoxia into canonical Wnt signaling, and opportunities to manipulate oxygen sensing to promote skeletal repair. RECENT FINDINGS: Oxygen sensing in osteocytes can confer a high bone mass phenotype in murine models; common and unique targets of HIF-1α and HIF-2α and lineage-specific deletion of oxygen sensing machinery suggest differentia utilization and requirement of HIF-α proteins in the differentiation from mesenchymal stem cell to osteoblast to osteocyte; oxygen-dependent but HIF-α-independent signaling may contribute to observed skeletal phenotypes...
February 6, 2019: Current Osteoporosis Reports
Lilian I Plotkin, Alyson L Essex, Hannah M Davis
PURPOSE OF REVIEW: The receptor for advanced glycation end products (RAGE) and several of its ligands have been implicated in the onset and progression of pathologies associated with aging, chronic inflammation, and cellular stress. In particular, the role of RAGE and its ligands in bone tissue during both physiological and pathological conditions has been investigated. However, the extent to which RAGE signaling regulates bone homeostasis and disease onset remains unclear. Further, RAGE effects in the different bone cells and whether these effects are cell-type specific is unknown...
January 26, 2019: Current Osteoporosis Reports
Betsabel Chicana, Cristine Donham, Alberto J Millan, Jennifer O Manilay
PURPOSE OF REVIEW: We reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion of Sost, Sostdc1, and Vhl affect hematopoietic cells. RECENT FINDINGS: B cell development is adversely affected in Sost-knockout mice and is more severely affected in Vhl-knockout mice...
April 2019: Current Osteoporosis Reports
Nancy E Lane
PURPOSE OF THIS REVIEW: The goal of the review is to provide an updated understanding of the pathophysiology of glucocorticoid-induced osteoporosis and treatment recommendations. RECENT FINDINGS: Glucocorticoids reduce osteoblast and osteocyte lifespan and activity and reduce the vascularity of the bone that together may explain the greater reductions in bone strength than those of bone mass. Treatments with parathyroid hormone fragments appear to reverse glucocorticoid-induced bone loss and fracture risk partially through maintaining bone vascularity and bone strength...
February 2019: Current Osteoporosis Reports
Olivier Lamy, Delphine Stoll, Bérengère Aubry-Rozier, Elena Gonzalez Rodriguez
PURPOSE OF REVIEW: Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it. RECENT FINDINGS: In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection...
February 2019: Current Osteoporosis Reports
Cheng Cheng, Dolores Shoback
PURPOSE OF REVIEW: Substantial advances have been made in understanding the biological basis of fracture healing. Yet, it is unclear whether the presence of osteoporosis or prior or current osteoporosis therapy influences the healing process or is associated with impaired healing. This review discusses the normal process of fracture healing and the role of osteoporosis and patient-specific factors in relation to fracture repair. RECENT FINDINGS: The definitive association of osteoporosis to impaired fracture healing remains inconclusive because of limited evidence addressing this point...
January 22, 2019: Current Osteoporosis Reports
Paige V Hinton, Susan M Rackard, Oran D Kennedy
PURPOSE OF REVIEW: Mechanical loading is an essential stimulus for skeletal tissues. Osteocytes are primarily responsible for sensing mechanical stimuli in bone and for orchestrating subsequent responses. This is critical for maintaining homeostasis, and responding to injury/disease. The osteocyte mechanotransduction pathway, and the downstream effects it mediates, is highly complex. In vivo models have proved invaluable in understanding this process. This review summarizes the commonly used models, as well as more recently developed ones, and describes how they are used to address emerging questions in the field...
December 2018: Current Osteoporosis Reports
J Rittweger, A Ireland, S Lüscher, L M Nocciolino, N Pilot, L Pisani, G R Cointry, J L Ferretti, R F Capozza
The human fibula responds to its mechanical environment differently from the tibia accordingly with foot usage. Fibula structure is unaffected by disuse, and is stronger concerning lateral bending in soccer players (who evert and rotate the foot) and weaker in long-distance runners (who jump while running) with respect to untrained controls, along the insertion region of peroneus muscles. These features, strikingly associated to the abilities of the fibulae of predator and prey quadrupeds to manage uneven surfaces and to store elastic energy to jump, respectively, suggest that bone mechanostat would control bone properties with high selective connotations beyond structural strength...
December 2018: Current Osteoporosis Reports
Ariella M Altman, Stuart M Sprague
PURPOSE OF REVIEW: Despite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation. RECENT FINDINGS: The pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism...
December 2018: Current Osteoporosis Reports
Stuart Silverman, Deborah T Gold
Patients at high risk of fracture often do not take medication for osteoporosis. Recent literature may give us some insights into why patients at high risk of fracture do not take medications for osteoporosis.
December 2018: Current Osteoporosis Reports
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