PDF
Abstract
Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery; however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Since the incidence of osteoporosis is expected to increase worldwide, orthopedic surgeons should pay more attention to comprehensive strategies for improving the poor prognosis of osteoporotic fractures. Herein, we highlight the molecular basis of osteoimmunology and bone mechanosensation in different healing phases of elderly osteoporotic fractures, guiding perioperative management to alleviate the unfavorable effects of insufficient mechanical loading, high inflammatory levels and pathogen infection. The well-informed pharmacologic and surgical intervention, including treatment with anti-inflammatory drugs and sufficient application of antibiotics, as well as bench-to-bedside strategies for bone augmentation and hardware selection, should be made according to a comprehensive understanding of bone biomechanical properties in addition to the remodeling status of osteoporotic bones, which is necessary for creating proper biological and mechanical environments for bone union and remodeling. Multidisciplinary collaboration will facilitate the improvement of overall osteoporotic care and reduction of secondary fracture incidence.
Cite this article
Download citation ▾
Yong Xie, Licheng Zhang, Qi Xiong, Yanpan Gao, Wei Ge, Peifu Tang.
Bench-to-bedside strategies for osteoporotic fracture: From osteoimmunology to mechanosensation.
Bone Research, 2019, 7(1): 25 DOI:10.1038/s41413-019-0066-7
| [1] |
Brown C. Osteoporosis: staying strong. Nature, 2017, 550:S15-s17
|
| [2] |
Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur. J. Rheumatol., 2017, 4:46-56
|
| [3] |
Yaacobi E, Sanchez D, Maniar H, Horwitz DS. Surgical treatment of osteoporotic fractures: an update on the principles of management. Injury, 2017, 48 Suppl. 7 S34-s40
|
| [4] |
Feron JM, Mauprivez R. Fracture repair: general aspects and influence of osteoporosis and anti-osteoporosis treatment. Injury, 2016, 47 Suppl. 1 S10-S14
|
| [5] |
von Ruden C, Augat P. Failure of fracture fixation in osteoporotic bone. Injury, 2016, 47 Suppl. 2 S3-S10
|
| [6] |
Smith DM, Khairi MR, Johnston CC Jr. The loss of bone mineral with aging and its relationship to risk of fracture. J. Clin. Investig., 1975, 56:311-318
|
| [7] |
Bernatz JT et al. Osteoporosis is common and undertreated prior to total joint arthroplasty. J. Arthroplast., 2019, 34:1347-1353
|
| [8] |
Singer A et al. Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin. Proc., 2015, 90:53-62
|
| [9] |
Clark D, Nakamura M, Miclau T, Marcucio R. Effects of aging on fracture healing. Curr. Osteoporos. Rep., 2017, 15:601-608
|
| [10] |
Baxter MA et al. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells, 2004, 22:675-682
|
| [11] |
Foulke BA, Kendal AR, Murray DW, Pandit H. Fracture healing in the elderly: a review. Maturitas, 2016, 92:49-55
|
| [12] |
Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos. Int.:, 2002, 13:97-104
|
| [13] |
Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simoes MJ, Cerri PS. Biology of bone tissue: structure, function, and factors that influence bone cells. BioMed. Res. Int., 2015, 2015:421746
|
| [14] |
Iwaniec UT, Turner RT. Influence of body weight on bone mass, architecture and turnover. J. Endocrinol., 2016, 230:R115-R130
|
| [15] |
van der Linden JC, Weinans H. Effects of microarchitecture on bone strength. Curr. Osteoporos. Rep., 2007, 5:56-61
|
| [16] |
Stock SR. The mineral–collagen interface in bone. Calcif. Tissue Int., 2015, 97:262-280
|
| [17] |
Tzaphlidou M. Bone architecture: collagen structure and calcium/phosphorus maps. J. Biol. Phys., 2008, 34:39-49
|
| [18] |
Guerado E et al. Bone mineral density aspects in the femoral neck of hip fracture patients. Injury, 2016, 47 Suppl. 1 S21-S24
|
| [19] |
Qi Z, Liu W, Lu J. The mechanisms underlying the beneficial effects of exercise on bone remodeling: roles of bone-derived cytokines and microRNAs. Prog. Biophys. Mol. Biol., 2016, 122:131-139
|
| [20] |
Katsimbri P.. The biology of normal bone remodelling. European Journal of Cancer Care, 2017, 26 6 e12740
|
| [21] |
Boyce BF, Rosenberg E, de Papp AE, Duong LT. The osteoclast, bone remodelling and treatment of metabolic bone disease. Eur. J. Clin. Investig., 2012, 42:1332-1341
|
| [22] |
Li C, Williams BO, Cao X, Wan M. LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling. Bone Res., 2014, 2:14006
|
| [23] |
Delaisse JM. The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. Bone. Rep., 2014, 3:561
|
| [24] |
Lai X et al. The dependences of osteocyte network on bone compartment, age, and disease. Bone Res., 2015, 3:15009
|
| [25] |
Hadjidakis DJ, Androulakis II. Bone remodeling. Ann. New Y. Acad. Sci., 2006, 1092:385-396
|
| [26] |
Watson EC, Adams RH. Biology of bone: the vasculature of the skeletal system. Cold Spring Harbor Perspect. Med., 2018, 8:a031559
|
| [27] |
Diab DL, Watts NB. Postmenopausal osteoporosis. Curr. Opin. Endocrinol. Diab. Obes., 2013, 20:501-509
|
| [28] |
Duque G, Troen BR. Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. J. Am. Geriatr. Soc., 2008, 56:935-941
|
| [29] |
Marie PJ. Bone cell senescence: mechanisms and perspectives. J. Bone Miner. Res., 2014, 29:1311-1321
|
| [30] |
Black DM, Rosen CJ. Clinical practice. Postmenopausal osteoporosis. New Engl. J. Med., 2016, 374:254-262
|
| [31] |
Yamagishi S. Role of advanced glycation end products (AGEs) in osteoporosis in diabetes. Curr. Drug Targets, 2011, 12:2096-2102
|
| [32] |
Chen H, Zhou X, Fujita H, Onozuka M, Kubo KY. Age-related changes in trabecular and cortical bone microstructure. Int. J. Endocrinol., 2013, 2013:213234
|
| [33] |
Osterhoff G et al. Bone mechanical properties and changes with osteoporosis. Injury, 2016, 47 Suppl. 2 S11-S20
|
| [34] |
Silva MJ. Biomechanics of osteoporotic fractures. Injury, 2007, 38 Suppl. 3 S69-S76
|
| [35] |
Marsell R, Einhorn TA. The biology of fracture healing. Injury, 2011, 42:551-555
|
| [36] |
Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat. Rev. Rheumatol., 2015, 11:45-54
|
| [37] |
Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat. Rev. Rheumatol., 2012, 8:133-143
|
| [38] |
Rothberg DL, Lee MA. Internal fixation of osteoporotic fractures. Curr. Osteoporos. Rep., 2015, 13:16-21
|
| [39] |
Lu C et al. Cellular basis for age-related changes in fracture repair. J. Orthop. Res., 2005, 23:1300-1307
|
| [40] |
Ozaki A, Tsunoda M, Kinoshita S, Saura R. Role of fracture hematoma and periosteum during fracture healing in rats: interaction of fracture hematoma and the periosteum in the initial step of the healing process. J. Orthop. Sci., 2000, 5:64-70
|
| [41] |
Chan JK et al. Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response. EMBO Mol. Med., 2015, 7:547-561
|
| [42] |
Timlin M et al. Fracture hematoma is a potent proinflammatory mediator of neutrophil function. J. Trauma, 2005, 58:1223-1229
|
| [43] |
Gibon E, Lu L, Goodman SB. Aging, inflammation, stem cells, and bone healing. Stem Cell Res. Ther., 2016, 7:44
|
| [44] |
Briot K, Geusens P, Em Bultink I, Lems WF, Roux C. Inflammatory diseases and bone fragility. Osteoporos. Int., 2017, 28:3301-3314
|
| [45] |
Weng N-p. Aging of the immune system: how much can the adaptive immune system adapt? Immunity, 2006, 24:495-499
|
| [46] |
McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood, 2001, 98:2498-2507
|
| [47] |
Frasca D et al. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J. Immunol., 2008, 180:5283-5290
|
| [48] |
Chong Y et al. CD27+ (memory) B cell decrease and apoptosis-resistant CD27− (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances. Int. Immunol., 2005, 17:383-390
|
| [49] |
Weksler ME, Goodhardt M, Szabo P. The effect of age on B cell development and humoral immunity. Springe. Semin. Immunopathol., 2002, 24:35-52
|
| [50] |
Swain S, Clise-Dwyer K, Haynes L. Homeostasis and the age-associated defect of CD4 T cells. Semin. Immunol., 2005, 17:370-377
|
| [51] |
Kovtun A et al. The crucial role of neutrophil granulocytes in bone fracture healing. Eur. Cells Mater., 2016, 32:152-162
|
| [52] |
Hearps AC et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell, 2012, 11:867-875
|
| [53] |
Sinder BP, Pettit AR, McCauley LK. Macrophages: their emerging roles in bone. J. Bone Miner. Res., 2015, 30:2140-2149
|
| [54] |
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat. Rev. Immunol., 2013, 13:875-887
|
| [55] |
Qian F et al. Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell, 2012, 11:104-110
|
| [56] |
Cope AP et al. Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J. Clin. Investig., 1994, 94:749-760
|
| [57] |
Frasca D et al. A molecular mechanism for TNF-α-mediated down-regulation of B cell responses. J. Immunol. (Baltim., MD: 1950), 2012, 188:279-286
|
| [58] |
Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE. Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells. Arthritis Res., 2001, 3:54-64
|
| [59] |
Isomaki P et al. Prolonged exposure of T cells to TNF down-regulates TCR zeta and expression of the TCR/CD3 complex at the cell surface. J. Immunol. (Baltim., MD: 1950), 2001, 166:5495-5507
|
| [60] |
Lim JC et al. TNFalpha contributes to diabetes impaired angiogenesis in fracture healing. Bone, 2017, 99:26-38
|
| [61] |
Oishi Y, Manabe I. Macrophages in age-related chronic inflammatory diseases. Npj Aging Mech. Dis., 2016, 2
|
| [62] |
Blanchette KA, Prabhakara R, Shirtliff ME, Wenke JC. Inhibition of fracture healing in the presence of contamination by Staphylococcus aureus: effects of growth state and immune response. J. Orthop. Res., 2017, 35:1845-1854
|
| [63] |
Kumar A, Tassopoulos AM, Li Q, Yu FS. Staphylococcus aureus protein A induced inflammatory response in human corneal epithelial cells. Biochem. Biophys. Res. Commun., 2007, 354:955-961
|
| [64] |
Olaru F, Jensen LE. Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop. J. Invest. Dermatol., 2010, 130:1866-1876
|
| [65] |
Stenzel W et al. An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance. J. Neuropathol. Exp. Neurol., 2005, 64:27-36
|
| [66] |
Liu H et al. Staphylococcus aureus epicutaneous exposure drives skin inflammation via IL-36-mediated T cell responses. Cell Host microbe, 2017, 22:653-666.e655
|
| [67] |
Hofbauer LC et al. Interleukin-1beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone, 1999, 25:255-259
|
| [68] |
Cenci S et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J. Clin. Investig., 2000, 106:1229-1237
|
| [69] |
Fuller K, Murphy C, Kirstein B, Fox SW, Chambers TJ. TNFalpha potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology, 2002, 143:1108-1118
|
| [70] |
Scheidt-Nave C et al. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J. Clin. Endocrinol. Metab., 2001, 86:2032-2042
|
| [71] |
Cuturi MC et al. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J. Exp. Med., 1987, 165:1581-1594
|
| [72] |
Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A. Tumor necrosis factor-α induces differentiation of and bone resorption by osteoclasts. J. Biol. Chem., 2000, 275:4858-4864
|
| [73] |
Gilbert L et al. Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology, 2000, 141:3956-3964
|
| [74] |
Kitaura H et al. Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. Clin. Dev. Immunol., 2013, 2013:8
|
| [75] |
Kim JH et al. The mechanism of osteoclast differentiation induced by IL-1. J. Immunol. (Baltim., MD: 1950), 2009, 183:1862-1870
|
| [76] |
Udagawa N et al. Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J. Exp. Med., 1995, 182:1461-1468
|
| [77] |
Chakravarti A, Raquil MA, Tessier P, Poubelle PE. Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption. Blood, 2009, 114:1633-1644
|
| [78] |
Allaeys I et al. Osteoblast retraction induced by adherent neutrophils promotes osteoclast bone resorption: implication for altered bone remodeling in chronic gout. Lab. Investig., 2011, 91:905-920
|
| [79] |
Takayanagi H et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature, 2000, 408:600-605
|
| [80] |
Schlundt C et al. Macrophages in bone fracture healing: their essential role in endochondral ossification. Bone, 2018, 106:78-89
|
| [81] |
Horowitz MC, Fretz JA, Lorenzo JA. How B cells influence bone biology in health and disease. Bone, 2010, 47:472-479
|
| [82] |
Yonou H et al. Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice. Cancer Res., 2003, 63:2096-2102
|
| [83] |
Catalano A et al. Pain in osteoporosis: from pathophysiology to therapeutic approach. Drugs aging, 2017, 34:755-765
|
| [84] |
Zuo Fuxing, Xiong Feng, Wang Xia, Li Xueyuan, Wang Renzhi, Ge Wei, Bao Xinjie. Intrastriatal Transplantation of Human Neural Stem Cells Restores the Impaired Subventricular Zone in Parkinsonian Mice. STEM CELLS, 2017, 35 6 1519-1531
|
| [85] |
Tatsumi S et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab., 2007, 5:464-475
|
| [86] |
Glatt V, Evans CH, Tetsworth K. A concert between biology and biomechanics: the influence of the mechanical environment on bone healing. Front. Physiol., 2016, 7:678
|
| [87] |
Plotkin LI, Bellido T. Osteocytic signalling pathways as therapeutic targets for bone fragility. Nat. Rev. Endocrinol., 2016, 12:593-605
|
| [88] |
Han MKL, de Rooij J. Converging and unique mechanisms of mechanotransduction at adhesion sites. Trends Cell Biol., 2016, 26:612-623
|
| [89] |
Sikavitsas VI, Temenoff JS, Mikos AG. Biomaterials and bone mechanotransduction. Biomaterials, 2001, 22:2581-2593
|
| [90] |
Xiao ZS, Quarles LD. Role of the polycytin-primary cilia complex in bone development and mechanosensing. Ann. New Y. Acad. Sci., 2010, 1192:410-421
|
| [91] |
Tu X et al. Osteocytes mediate the anabolic actions of canonical Wnt/beta-catenin signaling in bone. Proc. Natl Acad. Sci. USA, 2015, 112:E478-E486
|
| [92] |
Nguyen AM, Jacobs CR. Emerging role of primary cilia as mechanosensors in osteocytes. Bone, 2013, 54:196-204
|
| [93] |
Yavropoulou MP, Yovos JG. The molecular basis of bone mechanotransduction. J. Musculoskelet. Neuron. Interact., 2016, 16:221-236
|
| [94] |
Ranade SS, Syeda R, Patapoutian A. Mechanically activated ion channels. Neuron, 2015, 87:1162-1179
|
| [95] |
Lewis KJ et al. Osteocyte calcium signals encode strain magnitude and loading frequency in vivo. Proc. Natl Acad. Sci. USA, 2017, 114:11775-11780
|
| [96] |
Xu H et al. Connexin 43 channels are essential for normal bone structure and osteocyte viability. J. Bone Miner. Res., 2015, 30:436-448
|
| [97] |
Plotkin LI, Speacht TL, Donahue HJ. Cx43 and mechanotransduction in bone. Curr. Osteoporos. Rep., 2015, 13:67-72
|
| [98] |
Lynch ME, Fischbach C. Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations. Adv. Drug Deliv. Rev., 2014, 79-80:119-134
|
| [99] |
Fedorchak GR, Kaminski A, Lammerding J. Cellular mechanosensing: getting to the nucleus of it all. Prog. Biophys. Mol. Biol., 2014, 115:76-92
|
| [100] |
Kim CH, You L, Yellowley CE, Jacobs CR. Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling. Bone, 2006, 39:1043-1047
|
| [101] |
Temiyasathit S, Jacobs CR. Osteocyte primary cilium and its role in bone mechanotransduction. Ann. New Y. Acad. Sci., 2010, 1192:422-428
|
| [102] |
Goggin PM, Zygalakis KC, Oreffo RO, Schneider P. High-resolution 3D imaging of osteocytes and computational modelling in mechanobiology: insights on bone development, ageing, health and disease. Eur. Cells Mater., 2016, 31:264-295
|
| [103] |
Devlin MJ, Rosen CJ. The bone-fat interface: basic and clinical implications of marrow adiposity. The Lancet. Diab. Endocrinol., 2015, 3:141-147
|
| [104] |
Li J, Liu X, Zuo B, Zhang L. The role of bone marrow microenvironment in governing the balance between osteoblastogenesis and adipogenesis. Aging Dis., 2016, 7:514-525
|
| [105] |
Manolagas SC. The quest for osteoporosis mechanisms and rational therapies: how far we’ve come, how much further we need to go. J. Bone Miner. Res.:, 2018, 33:371-385
|
| [106] |
Goodman CA, Hornberger TA, Robling AG. Bone and skeletal muscle: key players in mechanotransduction and potential overlapping mechanisms. Bone, 2015, 80:24-36
|
| [107] |
Boyce BF, Xiu Y, Li J, Xing L, Yao Z. NF-kappaB-mediated regulation of osteoclastogenesis. Endocrinol. Metab., 2015, 30:35-44
|
| [108] |
Tarapore RS et al. NF-kappaB has a direct role in inhibiting Bmp- and Wnt-induced matrix protein expression. J. Bone Miner. Res., 2016, 31:52-64
|
| [109] |
Thompson WR, Rubin CT, Rubin J. Mechanical regulation of signaling pathways in bone. Gene, 2012, 503:179-193
|
| [110] |
Aguirre JI et al. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J. Biol. Chem., 2007, 282:25501-25508
|
| [111] |
Srinivasan S, Gross TS, Bain SD. Bone mechanotransduction may require augmentation in order to strengthen the senescent skeleton. Ageing Res. Rev., 2012, 11:353-360
|
| [112] |
Devlin MJ. Estrogen, exercise, and the skeleton. Evolut. Anthropol., 2011, 20:54-61
|
| [113] |
Loi F et al. Inflammation, fracture and bone repair. Bone, 2016, 86:119-130
|
| [114] |
Lin TH et al. NF-kappaB as a therapeutic target in inflammatory-associated bone diseases. Adv. protein Chem. Struct. Biol., 2017, 107:117-154
|
| [115] |
Salles MB et al. Evaluating nuclear factor NF-kappaB activation following bone trauma: a pilot study in a Wistar rats model. PLoS One, 2015, 10
|
| [116] |
Liu, T., Zhang, L., Joo, D. & Sun, S. C. NF-kappaB signaling in inflammation. Signal Transduct.Target. Ther. 2, https://doi.org/10.1038/sigtrans.2017.23 (2017).
|
| [117] |
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol., 2011, 7:33-42
|
| [118] |
Long P, Liu F, Piesco NP, Kapur R, Agarwal S. Signaling by mechanical strain involves transcriptional regulation of proinflammatory genes in human periodontal ligament cells in vitro. Bone, 2002, 30:547-552
|
| [119] |
Agarwal S et al. A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain. FASEB J., 2003, 17:899-901
|
| [120] |
Novack DV. Role of NF-kappaB in the skeleton. Cell Res., 2011, 21:169-182
|
| [121] |
Yu HS, Kim JJ, Kim HW, Lewis MP, Wall I. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues. J. Tissue Eng., 2016, 7:2041731415618342
|
| [122] |
Pires Bruno, Silva Rafael, Ferreira Gerson, Abdelhay Eliana. NF-kappaB: Two Sides of the Same Coin. Genes, 2018, 9 1 24
|
| [123] |
Wang L et al. Involvement of p38MAPK/NF-kappaB signaling pathways in osteoblasts differentiation in response to mechanical stretch. Ann. Biomed. Eng., 2012, 40:1884-1894
|
| [124] |
Wang L et al. Involvement of BMPs/Smad signaling pathway in mechanical response in osteoblasts. Cell. Physiol. Biochem.: Int. J. Exp. Cell Physiol., Biochem. Pharmacol., 2010, 26:1093-1102
|
| [125] |
Long P, Hu J, Piesco N, Buckley M, Agarwal S. Low magnitude of tensile strain inhibits IL-1beta-dependent induction of pro-inflammatory cytokines and induces synthesis of IL-10 in human periodontal ligament cells in vitro. J. Dent. Res., 2001, 80:1416-1420
|
| [126] |
Sauerschnig M et al. Effect of COX-2 inhibition on tendon-to-bone healing and PGE2 concentration after anterior cruciate ligament reconstruction. Eur. J. Med. Res., 2018, 23
|
| [127] |
Thorsen K, Kristoffersson AO, Lerner UH, Lorentzon RP. In situ microdialysis in bone tissue. Stimulation of prostaglandin E2 release by weight-bearing mechanical loading. J. Clin. Investig., 1996, 98:2446-2449
|
| [128] |
Cheung WH, Miclau T, Chow SK, Yang FF, Alt V. Fracture healing in osteoporotic bone. Injury, 2016, 47 Suppl. 2 S21-S26
|
| [129] |
Chow SK et al. Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats. Osteoporos. Int., 2016, 27:2989-3000
|
| [130] |
Thomas M, Puleo D. Infection, inflammation, and bone regeneration: a paradoxical relationship. J. Dent. Res., 2011, 90:1052-1061
|
| [131] |
Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J. Bone Jt. Surg. Am. Vol., 2011, 93:1583-1587
|
| [132] |
Grundnes O, Reikeras O. The role of hematoma and periosteal sealing for fracture healing in rats. Acta Orthop. Scand., 1993, 64:47-49
|
| [133] |
Yuasa M et al. Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification. J. Clin. Investig., 2015, 125:3723
|
| [134] |
Dohan Ehrenfest DM et al. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J., 2014, 4:3-9
|
| [135] |
Xie H et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat. Med., 2014, 20:1270-1278
|
| [136] |
Wagatsuma A. Effect of aging on expression of angiogenesis-related factors in mouse skeletal muscle. Exp. Gerontol., 2006, 41:49-54
|
| [137] |
Kallala R et al. In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture healing. Expert Opin. Drug Saf., 2012, 11:15-32
|
| [138] |
Antoci V Jr., Adams CS, Hickok NJ, Shapiro IM, Parvizi J. Antibiotics for local delivery systems cause skeletal cell toxicity in vitro. Clin. Orthop. Relat. Res., 2007, 462:200-206
|
| [139] |
Cope AP et al. Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling. J. Exp. Med., 1997, 185:1573-1584
|
| [140] |
Chopin F et al. Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann. Rheum. Dis., 2008, 67:353-357
|
| [141] |
Marotte H et al. A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab. Arthritis Res. Ther., 2007, 9:R61
|
| [142] |
Roggia C 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. Proc. Natl Acad. Sci. USA, 2001, 98:13960-13965
|
| [143] |
Kimble RB et al. Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. Endocrinology, 1995, 136:3054-3061
|
| [144] |
Gao Y et al. Estrogen prevents bone loss through transforming growth factor β signaling in T cells. Proc. Natl Acad. Sci. USA, 2004, 101:16618-16623
|
| [145] |
Scherrer CB, Mannion AF, Kyburz D, Vogt M. & Kramers-de Quervain, I. A. Infection risk after orthopedic surgery in patients with inflammatory rheumatic diseases treated with immunosuppressive drugs. Arthritis Care Res., 2013, 65:2032-2040
|
| [146] |
Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann. Clin. Biochem., 2014, 51:189-202
|
| [147] |
Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin. Proc., 2008, 83:1032-1045
|
| [148] |
Dirschl DR, Rustom H. Practice patterns and performance in U.S. fracture liaison programs: an analysis of > 32,000 patients from the own the bone program. J. Bone Jt. Surg. Am. Vol., 2018, 100:680-685
|
| [149] |
Hauser M, Siegrist M, Keller I, Hofstetter W. Healing of fractures in osteoporotic bones in mice treated with bisphosphonates—a transcriptome analysis. Bone, 2018, 112:107-119
|
| [150] |
Zaheer S, LeBoff M, Lewiecki EM. Denosumab for the treatment of osteoporosis. Expert Opin. Drug Metab. Toxicol., 2015, 11:461-470
|
| [151] |
Bone HG et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. The Lancet. Diabetes Endocrinol., 2017, 5:513-523
|
| [152] |
Silverman SL, Azria M. The analgesic role of calcitonin following osteoporotic fracture. Osteoporos. Int., 2002, 13:858-867
|
| [153] |
Liu Y et al. Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis. J. Control. Release., 2019, 304:39-50
|
| [154] |
Ren L, Wang W. Effect of risedronate on femoral periprosthetic bone loss following total hip replacement: a systematic review and meta-analysis. Medicine, 2018, 97
|
| [155] |
Redlich K et al. Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis. Am. J. Pathol., 2004, 164:543-555
|
| [156] |
Thompson WR et al. Osteocyte specific responses to soluble and mechanical stimuli in a stem cell derived culture model. Sci. Rep., 2015, 5
|
| [157] |
Cianferotti L, D’Asta F, Brandi ML. A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis. Ther. Adv. Musculoskelet. Dis., 2013, 5:127-139
|
| [158] |
Iolascon G et al. Bone quality and bone strength: benefits of the bone-forming approach. Clin. Cases Miner. Bone Metab., 2014, 11:20-24
|
| [159] |
Langdahl BL et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet, 2017, 390:1585-1594
|
| [160] |
MacFarlane Elena Gallo, Haupt Julia, Dietz Harry C., Shore Eileen M.. TGF-β Family Signaling in Connective Tissue and Skeletal Diseases. Cold Spring Harbor Perspectives in Biology, 2017, 9 11 a022269
|
| [161] |
Rys JP, Monteiro DA, Alliston T. Mechanobiology of TGFbeta signaling in the skeleton. Matrix Biol.: J. Int. Soc. Matrix Biol., 2016, 52:413-425
|
| [162] |
Li M, Liu X, Liu X, Ge B. Calcium phosphate cement with BMP-2-loaded gelatin microspheres enhances bone healing in osteoporosis: a pilot study. Clin. Orthop. Relat. Res., 2010, 468:1978-1985
|
| [163] |
Hu MH et al. Polymethylmethacrylate augmentation of the pedicle screw: the cement distribution in the vertebral body. Eur. Spine J., 2011, 20:1281-1288
|
| [164] |
Bettencourt A, Almeida AJ. Poly(methyl methacrylate) particulate carriers in drug delivery. J. Microencapsul., 2012, 29:353-367
|
| [165] |
Webb JC, Spencer RF. The role of polymethylmethacrylate bone cement in modern orthopaedic surgery. J. bone Jt. Surg. Br. Vol., 2007, 89:851-857
|
| [166] |
Arora M, Chan EK, Gupta S, Diwan AD. Polymethylmethacrylate bone cements and additives: a review of the literature. World J. Orthop., 2013, 4:67-74
|
| [167] |
Watson JT, Nicolaou DA. Orthobiologics in the augmentation of osteoporotic fractures. Curr. Osteoporos. Rep., 2015, 13:22-29
|
| [168] |
Schumaier A, Grawe B. Proximal humerus fractures: evaluation and management in the elderly patient. Geriatr. Orthop. Surg. Rehabilit., 2018, 9:2151458517750516
|
| [169] |
Chan ME, Uzer G, Rubin CT. The potential benefits and inherent risks of vibration as a non-drug therapy for the prevention and treatment of osteoporosis. Curr. Osteoporos. Rep., 2013, 11:36-44
|
| [170] |
Nagaraja MP, Jo H. The role of mechanical stimulation in recovery of bone loss-high versus low magnitude and frequency of force. Life, 2014, 4:117-130
|
| [171] |
Griffin, X. L., Parsons, N., Costa, M. L. & Metcalfe, D. Ultrasound and shockwave therapy for acute fractures in adults. Cochrane Database Syst. Rev. Cd008579, https://doi.org/10.1002/14651858.CD008579.pub3 (2014).
|
| [172] |
Miller PD. The history of bone densitometry. Bone, 2017, 104:4-6
|
| [173] |
Seeman E. Pathogenesis of bone fragility in women and men. Lancet, 2002, 359:1841-1850
|
| [174] |
de Bakker CMJ, Tseng WJ, Li Y, Zhao H, Liu XS. Clinical evaluation of bone strength and fracture risk. Curr. Osteoporos. Rep., 2017, 15:32-42
|
| [175] |
Silva BC et al. Trabecular bone score (TBS)—a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab., 2013, 98:1963-1970
|
| [176] |
Harvey NC et al. Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone, 2015, 78:216-224
|
| [177] |
Shevroja E et al. Use of trabecular bone score (TBS) as a complementary approach to dual-energy X-ray absorptiometry (DXA) for fracture risk assessment in clinical practice. J. Clin. Densitom., 2017, 20:334-345
|
| [178] |
Iki M et al. Trabecular bone score may improve FRAX(R) prediction accuracy for major osteoporotic fractures in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study. Osteoporos. Int., 2015, 26:1841-1848
|
| [179] |
Brandi ML. Microarchitecture, the key to bone quality. Rheumatology, 2009, 48 Suppl. 4 iv3-iv8
|
| [180] |
Eckert JA, Jaeger S, Klotz MC, Schwarze M, Bitsch RG. Can intraoperative measurement of bone quality help in decision making for cementless unicompartmental knee arthroplasty? Knee, 2018, 25:609-616
|
| [181] |
Seebeck J et al. Effect of cortical thickness and cancellous bone density on the holding strength of internal fixator screws. J. Orthop. Res., 2004, 22:1237-1242
|
| [182] |
Shea TM et al. Designs and techniques that improve the pullout strength of pedicle screws in osteoporotic vertebrae: current status. BioMed. Res. Int., 2014, 2014:748393
|
| [183] |
Wang T, Boone C, Behn AW, Ledesma JB, Bishop JA. Cancellous screws are biomechanically superior to cortical screws in metaphyseal bone. Orthopedics, 2016, 39:e828-e832
|
| [184] |
Cornell CN. Internal fracture fixation in patients with osteoporosis. J. Am. Acad. Orthop. Surg., 2003, 11:109-119
|
| [185] |
Ab-Lazid R, Perilli E, Ryan MK, Costi JJ, Reynolds KJ. Does cancellous screw insertion torque depend on bone mineral density and/or microarchitecture? J. Biomech., 2014, 47:347-353
|
| [186] |
Karim L, Vashishth D. Role of trabecular microarchitecture in the formation, accumulation, and morphology of microdamage in human cancellous bone. J. Orthop. Res., 2011, 29:1739-1744
|
| [187] |
Greiwe RM, Archdeacon MT. Locking plate technology: current concepts. J. Knee Surg., 2007, 20:50-55
|
| [188] |
Miranda MA. Locking plate technology and its role in osteoporotic fractures. Injury, 2007, 38 Suppl. 3 S35-S39
|
| [189] |
Kralinger F et al. The influence of local bone density on the outcome of one hundred and fifty proximal humeral fractures treated with a locking plate. J. Bone Jt. Surg. Am. Vol., 2014, 96:1026-1032
|
| [190] |
Johanson NA, Litrenta J, Zampini JM, Kleinbart F, Goldman HM. Surgical treatment options in patients with impaired bone quality. Clin. Orthop. Relat. Res., 2011, 469:2237-2247
|
| [191] |
Ito K, Hungerbuhler R, Wahl D, Grass R. Improved intramedullary nail interlocking in osteoporotic bone. J. Orthop. Trauma, 2001, 15:192-196
|
| [192] |
McKee MD et al. A multicenter, prospective, randomized, controlled trial of open reduction-internal fixation versus total elbow arthroplasty for displaced intra-articular distal humeral fractures in elderly patients. J. Shoulder Elb. Surg., 2009, 18:3-12
|
| [193] |
Boraiah S, Ragsdale M, Achor T, Zelicof S, Asprinio DE. Open reduction internal fixation and primary total hip arthroplasty of selected acetabular fractures. J. Orthop. Trauma, 2009, 23:243-248
|
| [194] |
Goldhahn J, Suhm N, Goldhahn S, Blauth M, Hanson B. Influence of osteoporosis on fracture fixation-a systematic literature review. Osteoporos. Int., 2008, 19:761-772
|
| [195] |
Seebeck J, Goldhahn J, Morlock MM, Schneider E. Mechanical behavior of screws in normal and osteoporotic bone. Osteoporos. Int., 2005, 16 Suppl. 2 S107-S111
|
| [196] |
McAndrew CM et al. Local bone quality measurements correlates with maximum screw torque at the femoral diaphysis. Clin. Biomech., 2018, 52:95-99
|
| [197] |
Parkinson IH, Fazzalari NL. Whole bone geometry and bone quality in distal forearm fracture. J. Orthop. Trauma, 2008, 22:S59-S65
|
| [198] |
Cornell CN, Ayalon O. Evidence for success with locking plates for fragility fractures. HSS J., 2011, 7:164-169
|
| [199] |
Ricci WM, Tornetta P, Borrelli J Jr. Lag screw fixation of medial malleolar fractures: a biomechanical, radiographic, and clinical comparison of unicortical partially threaded lag screws and bicortical fully threaded lag screws. J. Orthop. trauma, 2012, 26:602-606
|
| [200] |
Egol KA, Kubiak EN, Fulkerson E, Kummer FJ, Koval KJ. Biomechanics of locked plates and screws. J. Orthop. trauma, 2004, 18:488-493
|
| [201] |
Babhulkar S. Unstable trochanteric fractures: Issues and avoiding pitfalls. Injury, 2017, 48:803-818
|
| [202] |
Oheim R, Schinke T, Amling M, Pogoda P. Can we induce osteoporosis in animals comparable to the human situation? Injury, 2016, 47 Suppl. 1 S3-S9
|
| [203] |
Sproul RC, Iyengar JJ, Devcic Z, Feeley BT. A systematic review of locking plate fixation of proximal humerus fractures. Injury, 2011, 42:408-413
|
| [204] |
Mellibovsky L et al. Bone tissue properties measurement by reference point indentation in glucocorticoid-induced osteoporosis. J. Bone Miner. Res., 2015, 30:1651-1656
|
| [205] |
Sanchez-Riera L et al. Osteoporosis and fragility fractures. Best Pract. Res. Clin. Rheumatol., 2010, 24:793-810
|
Funding
National Natural Science Foundation of China (National Science Foundation of China)(81401809)
Beijing Nova Program(Z171100001117110)
Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)(7192127)
CAMS Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-3-001)