Disorders of bone remodeling.

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms.

[1]  N. Holbrook,et al.  Oxidants, oxidative stress and the biology of ageing , 2000, Nature.

[2]  R. Pacifici.  Cytokines, estrogen, and postmenopausal osteoporosis--the second decade. , 1998, Endocrinology.

[3]  D. Lacey,et al.  Printed in U.S.A. Copyright © 1999 by The Endocrine Society Stimulation of Osteoprotegerin Ligand and Inhibition of Osteoprotegerin Production by Glucocorticoids in , 2022 .

[4]  G Shimamoto,et al.  Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density , 1997, Cell.

[5]  J. Tolar,et al.  Osteopetrosis. , 2004, The New England journal of medicine.

[6]  J. McDonald,et al.  Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis , 2010, Journal of Bone and Mineral Metabolism.

[7]  F. Albright,et al.  POSTMENOPAUSAL OSTEOPOROSIS: ITS CLINICAL FEATURES , 1941 .

[8]  H J Donahue,et al.  Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. , 2000, Journal of biomechanical engineering.

[9]  T. Clemens,et al.  Mode of Growth Hormone Action in Osteoblasts* , 2007, Journal of Biological Chemistry.

[10]  A. Parfitt.  Osteonal and hemi‐osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone , 1994, Journal of cellular biochemistry.

[11]  L. Raisz.  Hormonal regulation of bone growth and remodelling. , 2007, Ciba Foundation symposium.

[12]  R. Baron,et al.  Wnt signaling and the regulation of bone mass , 2007, Current osteoporosis reports.

[13]  A. M. Parfitt,et al.  Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis , 2001 .

[14]  W. R. Taylor,et al.  Activation of Extracellular Signal–Regulated Kinase Is Involved in Mechanical Strain Inhibition of RANKL Expression in Bone Stromal Cells , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  H. Genant,et al.  Cortical and Trabecular Bone Mineral Loss From the Spine and Hip in Long‐Duration Spaceflight , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  A. Parfitt.  CHAPTER 5 – Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis , 2008 .

[17]  G. Mundy,et al.  The effects of TGF-beta on bone. , 1991, Ciba Foundation symposium.

[18]  B. Komm,et al.  Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. , 1988, Science.

[19]  David L. Lacey,et al.  Osteoclast differentiation and activation , 2003, Nature.

[20]  B. Riggs,et al.  The Type I/Type II Model for Involutional Osteoporosis: Update and Modification Based on New Observations , 2001 .

[21]  B. Maldague,et al.  Fat conversion of femoral marrow in glucocorticoid-treated patients: a cross-sectional and longitudinal study with magnetic resonance imaging. , 1999, Arthritis and rheumatism.

[22]  Brian R. Wong,et al.  TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells* , 1997, The Journal of Biological Chemistry.

[23]  G. Karsenty,et al.  The osteoblast: a sophisticated fibroblast under central surveillance. , 2000, Science.

[24]  C S Leach,et al.  Collagen cross-link excretion during space flight and bed rest. , 1998, The Journal of clinical endocrinology and metabolism.

[25]  R. Pacifici,et al.  Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss in vivo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  E. Schwarz,et al.  RANK Signaling Is Not Required for TNFα‐Mediated Increase in CD11bhi Osteoclast Precursors but Is Essential for Mature Osteoclast Formation in TNFα‐Mediated Inflammatory Arthritis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  H. Malluche,et al.  Bone disease after renal transplantation , 2010, Nature Reviews Nephrology.

[28]  M. Horowitz.  Cytokines and estrogen in bone: anti-osteoporotic effects. , 1993, Science.

[29]  A. Parfitt.  Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. , 2002, Bone.

[30]  Kay Dickersin,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2000, NIH consensus statement.

[31]  S. Teitelbaum,et al.  Chapter 3 – Osteoclast Biology , 2001 .

[32]  H. Yeo,et al.  NFATc1: A Novel Anabolic Therapeutic Target for Osteoporosis , 2006, Annals of the New York Academy of Sciences.

[33]  T. Martin,et al.  Tumor Necrosis Factor (cid:97) Stimulates Osteoclast Differentiation by a Mechanism Independent of the ODF/RANKL–RANK Interaction , 2022 .

[34]  L. Bonewald.  Osteocytes as Dynamic Multifunctional Cells , 2007, Annals of the New York Academy of Sciences.

[35]  Koichi Matsuo,et al.  Osteoclast-osteoblast communication. , 2008, Archives of biochemistry and biophysics.

[36]  A. Parfitt.  The Bone Remodeling Compartment: A Circulatory Function for Bone Lining Cells , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  A. Zallone,et al.  FSH Directly Regulates Bone Mass , 2006, Cell.

[38]  J. McDonald,et al.  Calmodulin and Calmodulin-dependent Kinase IIα Regulate Osteoblast Differentiation by Controlling c-fos Expression* , 2005, Journal of Biological Chemistry.

[39]  M. K. Young,et al.  Osteoclasts secrete the chemotactic cytokine mim-1. , 2001, Biochemical and biophysical research communications.

[40]  G. Mundy,et al.  Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β , 1996, Nature Medicine.

[41]  E. Canalis,et al.  Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. , 1990, The Journal of biological chemistry.

[42]  T. Martin,et al.  New mechanisms and targets in the treatment of bone fragility. , 2007, Clinical science.

[43]  D. Hartmann,et al.  Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. , 1997, Bone.

[44]  Yi Tang,et al.  TGF-β1-induced Migration of Bone Mesenchymal Stem Cells Couples Bone Resorption and Formation , 2009, Nature Medicine.

[45]  P. Delmas,et al.  Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[46]  P. Lips,et al.  Vitamin d-related disorders , 2013 .

[47]  J. McDonald,et al.  Calmodulin—an often‐ignored signal in osteoclasts , 2010, Annals of the New York Academy of Sciences.

[48]  E. Siris,et al.  CHAPTER 73 – Estrogen Analogues: Selective Estrogen Receptor Modulators and Phytoestrogens , 2008 .

[49]  S. Manolagas,et al.  Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. , 2000, Endocrine reviews.

[50]  L. Raisz.  Pathogenesis of osteoporosis: concepts, conflicts, and prospects. , 2005, The Journal of clinical investigation.

[51]  D. Lacey,et al.  The Osteoclast Differentiation Factor Osteoprotegerin-Ligand Is Essential for Mammary Gland Development , 2000, Cell.

[52]  J. Bilezikian,et al.  Glucocorticoid-induced osteoporosis: pathophysiology and therapy , 2007, Osteoporosis International.

[53]  J. McDonald,et al.  Differential effects of tamoxifen‐like compounds on osteoclastic bone degradation, H+‐ATPase activity, calmodulin‐dependent cyclic nucleotide phosphodiesterase activity, and calmodulin binding , 1997, Journal of cellular biochemistry.

[54]  R. Steinman,et al.  TRANCE (Tumor Necrosis Factor [TNF]-related Activation-induced Cytokine), a New TNF Family Member Predominantly Expressed in T cells, Is a Dendritic Cell–specific Survival Factor , 1997, The Journal of experimental medicine.

[55]  A. Boskey,et al.  Chapter 6. The Composition of Bone , 2009 .

[56]  Ego Seeman,et al.  Bone modeling and remodeling. , 2009, Critical reviews in eukaryotic gene expression.

[57]  S. Morony,et al.  OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis , 1999, Nature.

[58]  D. Lacey,et al.  Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation , 1998, Cell.

[59]  G. Eknoyan,et al.  Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). , 2006, Kidney international.

[60]  Eric S. Orwoll,et al.  The nature of osteoporosis , 2021, Marcus and Feldman's Osteoporosis.

[61]  Dirk L. Ypey,et al.  Cell membrane stretch in osteoclasts triggers a self-reinforcing Ca2+ entry pathway , 1995, Pflügers Archiv.

[62]  Toshio Matsumoto,et al.  17β-Estradiol Stimulates Expression of Osteoprotegerin by a Mouse Stromal Cell Line, ST-2, via Estrogen Receptor-α. , 2001, Endocrinology.

[63]  G G Klee,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Relationship of Serum Sex Steroid Levels and Bone Turnover Markers with Bone Mineral Density in Men and Women: A Key Role for Bioavailable Estroge , 2022 .

[64]  S. Mohan,et al.  Insulin-like growth factor system components and the coupling of bone formation to resorption. , 1996, Hormone research.

[65]  G. Mundy.  The Effects of TGF‐β on Bone , 2007 .

[66]  G. Milon,et al.  Decreased Erythropoiesis: The Origin of the BCG Induced Anaemia in Mice , 1981, British journal of haematology.

[67]  W. Nelp,et al.  Long-term calcitonin therapy in postmenopausal osteoporosis. , 1984, Metabolism: clinical and experimental.

[68]  E. Canalis.  Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. , 1983, Endocrinology.

[69]  K. Satomura,et al.  Circulating Skeletal Stem Cells , 2001, The Journal of cell biology.

[70]  Minqi Li,et al.  Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. , 2007, Cell metabolism.

[71]  J. Braun,et al.  Die glukokortikoidinduzierte Osteoporose , 2001, Der Orthopäde.

[72]  I. Robinson,et al.  Bone marrow adipocytes: a neglected target tissue for growth hormone. , 2002, Endocrinology.

[73]  R. Recker,et al.  Menopausal changes in bone remodeling. , 1978, The Journal of laboratory and clinical medicine.

[74]  S. Takeshita,et al.  TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. , 2000, The Journal of clinical investigation.

[75]  R. Jilka,et al.  Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. , 1998, Bone.

[76]  Chao Liu,et al.  Boning up on Wolff's Law: Mechanical Regulation of the Cells That Make and Maintain Bone , 2022 .

[77]  A. Auerbach,et al.  Multiple forms of mechanosensitive ion channels in osteoblast-like cells , 1990, Pflügers Archiv.

[78]  B. L. Riggs,et al.  Role of the vitamin D‐endocrine system in the pathophysiology of postmenopausal osteoporosis , 2003, Journal of cellular biochemistry.

[79]  R. Steinman,et al.  TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation , 1999, The Journal of experimental medicine.

[80]  J. Pike,et al.  Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[81]  S. Manolagas.  From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. , 2010, Endocrine reviews.

[82]  R. Weinstein,et al.  Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. , 2006, Endocrinology.

[83]  M. Waters,et al.  Growth hormone and insulin-like growth factor I induce bone morphogenetic proteins 2 and 4: a mediator role in bone and tooth formation? , 1998, Endocrinology.

[84]  N. Yasui,et al.  Disuse osteoporosis. , 2001, The journal of medical investigation : JMI.

[85]  A. Haeseler,et al.  Central control of fever and female body temperature by RANKL/RANK , 2009, Nature.

[86]  D. Kiel,et al.  Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study. , 1998, The Journal of clinical endocrinology and metabolism.

[87]  P. Chambon,et al.  Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts , 2007, Cell.

[88]  T. Plesner,et al.  A physical mechanism for coupling bone resorption and formation in adult human bone , 2008 .

[89]  Zhao-Jun Liu,et al.  Trafficking and differentiation of mesenchymal stem cells , 2009, Journal of cellular biochemistry.

[90]  L. Mosekilde,et al.  Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro , 1993, Calcified Tissue International.

[91]  Majd Zayzafoon,et al.  Microgravity: the immune response and bone , 2005, Immunological reviews.

[92]  C. Cooper,et al.  Use of Inhaled Corticosteroids and Risk of Fractures , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[93]  J. McDonald,et al.  Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. , 2007, Bone.

[94]  J. Brewer,et al.  Glucocorticoids suppress bone formation via the osteoclast. , 2006, The Journal of clinical investigation.

[95]  R. Dubose,et al.  A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function , 1997, Nature.

[96]  G. Passeri,et al.  17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. , 1992, The Journal of clinical investigation.

[97]  D. Lacey,et al.  Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. , 2003, The Journal of clinical investigation.

[98]  S. Morony,et al.  osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. , 1998, Genes & development.

[99]  R. Globus,et al.  Role for beta1 integrins in cortical osteocytes during acute musculoskeletal disuse. , 2008, Matrix biology : journal of the International Society for Matrix Biology.

[100]  A. Parfitt,et al.  Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. , 1998, The Journal of clinical investigation.

[101]  G. Mazziotti,et al.  Growth hormone, insulin-like growth factors, and the skeleton. , 2008, Endocrine reviews.

[102]  F. Singer.  Paget disease: when to treat and when not to treat , 2009, Nature Reviews Rheumatology.

[103]  J. Brewer,et al.  Glucocorticoids and the osteoclast. , 2007, Annals of the New York Academy of Sciences.

[104]  D. Kalu,et al.  Calcium Absorption and Bone Loss in Ovariectomized Rats Fed Varying Levels of Dietary Calcium , 1999, Calcified Tissue International.

[105]  N. Watts,et al.  Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis , 2013 .

[106]  M. Bouxsein,et al.  CHAPTER 2 – The Nature of Osteoporosis , 2008 .

[107]  T. Martin,et al.  Molecular mechanisms in coupling of bone formation to resorption. , 2009, Critical reviews in eukaryotic gene expression.

[108]  R. Pacifici,et al.  Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. , 2000, The Journal of clinical investigation.

[109]  P. Pelicci,et al.  Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? , 2007, Nature Reviews Molecular Cell Biology.

[110]  R. Pacifici.  Editorial: Cytokines, Estrogen, and Postmenopausal Osteoporosis-The Second Decade. , 1998, Endocrinology.

[111]  M. Stefanick.  Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. , 2005, The American journal of medicine.

[112]  K Yano,et al.  Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[113]  A. Fischer,et al.  Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report , 2003, Bone Marrow Transplantation.

[114]  H. Broxmeyer,et al.  Increased osteoclast development after estrogen loss: mediation by interleukin-6. , 1992, Science.

[115]  Kozo Nakamura,et al.  RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β , 2002, Nature.

[116]  E. Siris.  Extensive personal experience: Paget's disease of bone. , 1995, The Journal of clinical endocrinology and metabolism.

[117]  T. Nagy,et al.  Osteoclast apoptosis: the role of Fas in vivo and in vitro. , 2003, Endocrinology.

[118]  Efthimia K Basdra,et al.  Mechanotransduction in osteoblast regulation and bone disease. , 2009, Trends in molecular medicine.

[119]  S. Khosla.  Update in male osteoporosis. , 2010, The Journal of clinical endocrinology and metabolism.

[120]  E. Lewiecki.  Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis. , 2009, Journal of women's health.

[121]  S. Lotinun,et al.  Dose—Response Effects of Intermittent PTH on Cancellous Bone in Hindlimb Unloaded Rats , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[122]  S. Boonen,et al.  Teriparatide or alendronate in glucocorticoid-induced osteoporosis. , 2007, The New England journal of medicine.

[123]  M. Rubin,et al.  The use of parathyroid hormone in the treatment of osteoporosis , 2007, Reviews in Endocrine and Metabolic Disorders.

[124]  Jacques P. Brown,et al.  Gene expression profile in osteoclasts from patients with Paget's disease of bone. , 2010, Bone.

[125]  F. Ross,et al.  Estrogen Decreases Osteoclast Formation by Down-regulating Receptor Activator of NF-κB Ligand (RANKL)-induced JNK Activation* , 2001, The Journal of Biological Chemistry.

[126]  J. McDonald,et al.  The role of calmodulin in the regulation of osteoclastogenesis. , 2003, Endocrinology.

[127]  W. Dougall,et al.  RANK is essential for osteoclast and lymph node development. , 1999, Genes & development.

[128]  A. Peretz,et al.  Serum osteocalcin in the assessment of corticosteroid induced osteoporosis. Effect of long and short term corticosteroid treatment. , 1989, The Journal of rheumatology.

[129]  A. Parfitt.  Chapter 36 – Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis , 2013 .

[130]  M. Almeida,et al.  Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription* , 2007, Journal of Biological Chemistry.

[131]  B. Riggs,et al.  Circulating osteoblast-lineage cells in humans. , 2005, The New England journal of medicine.

[132]  S. Khosla,et al.  Skeletal stem/osteoprogenitor cells: Current concepts, alternate hypotheses, and relationship to the bone remodeling compartment , 2008, Journal of cellular biochemistry.

[133]  H W Wahner,et al.  Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes. , 1982, The Journal of clinical investigation.

[134]  E. Puscheck,et al.  Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[135]  A. Hofman,et al.  Association between an insulin-like growth factor I gene promoter polymorphism and bone mineral density in the elderly: the Rotterdam Study. , 2003, The Journal of clinical endocrinology and metabolism.

[136]  B. Riggs,et al.  Pathophysiology of age-related bone loss and osteoporosis. , 2005, Endocrinology and metabolism clinics of North America.

[137]  P. Miller.  Denosumab: Anti-RANKL antibody , 2009, Current osteoporosis reports.

[138]  R. Eastell,et al.  Cancellous bone remodeling in type i (postmenopausal) osteoporosis: Quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[139]  T. Plesner,et al.  Myeloma cell‐induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast‐myeloma hybrid cells , 2010, British journal of haematology.

[140]  S. Teitelbaum,et al.  Bone resorption by osteoclasts. , 2000, Science.

[141]  J. McDonald,et al.  Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells , 2013, Journal of cellular biochemistry.

[142]  H. Kishimoto.  [Bisphosphonates: pharmacology and use in the treatment of osteoporosis]. , 2002, Nihon rinsho. Japanese journal of clinical medicine.

[143]  Majd Zayzafoon,et al.  RhoA and Cytoskeletal Disruption Mediate Reduced Osteoblastogenesis and Enhanced Adipogenesis of Human Mesenchymal Stem Cells in Modeled Microgravity , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[144]  S. Teitelbaum,et al.  Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[145]  Janet Rubin,et al.  Molecular pathways mediating mechanical signaling in bone. , 2006, Gene.

[146]  E. Siris,et al.  Clinical Vignette: Natural History of Untreated Paget's Disease of the Tibia , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[147]  R. Jilka,et al.  Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. , 1995, The New England journal of medicine.

[148]  D. Pavlović,et al.  Chronic kidney disease mineral bone disorder , 2015 .

[149]  W R Taylor,et al.  Osteoclastogenesis is repressed by mechanical strain in an in vitro model , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[150]  Sundeep Khosla,et al.  Sex steroids and the construction and conservation of the adult skeleton. , 2002, Endocrine reviews.

[151]  R. Ritchie,et al.  Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. , 2008, Arthritis and rheumatism.

[152]  Flemming Melsen,et al.  Cancellous Bone Remodeling Occurs in Specialized Compartments Lined by Cells Expressing Osteoblastic Markers , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[153]  Robert S. Balaban,et al.  Mitochondria, Oxidants, and Aging , 2005, Cell.

[154]  T. Martin,et al.  Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. , 1999, Endocrine reviews.

[155]  A. D. Bakker,et al.  The role of osteocytes in bone mechanotransduction , 2009, Osteoporosis International.

[156]  R. Steinman,et al.  TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. , 1999, Journal of immunology.

[157]  Xu Feng.  Regulatory roles and molecular signaling of TNF family members in osteoclasts. , 2005, Gene.

[158]  K. Saag,et al.  CHAPTER 44 – Glucocorticoid-Induced Osteoporosis , 2008 .

[159]  Y. Azuma,et al.  Tumor Necrosis Factor-α Induces Differentiation of and Bone Resorption by Osteoclasts* , 2000, The Journal of Biological Chemistry.

[160]  D. Bidwell,et al.  Formation , 2006, Revue Francophone d'Orthoptie.

[161]  T. Martin,et al.  Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. , 1991, Endocrinology.

[162]  S. Doty,et al.  Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[163]  Scott M Smith,et al.  Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended‐Duration Space Flight on the Mir Space Station , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.