Inflammatory bone loss: pathogenesis and therapeutic intervention (original) (raw)
Sims, N. A. & Gooi, J. H. Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin. Cell Dev. Biol.19, 444–451 (2008). ArticleCASPubMed Google Scholar
Bodine, P. V. & Komm, B. S. Wnt signaling and osteoblastogenesis. Rev. Endocr. Metab. Disord.7, 33–39 (2006). ArticleCASPubMed Google Scholar
Yavropoulou, M. P. & Yovos, J. G. Osteoclastogenesis — current knowledge and future perspectives. J. Musculoskelet. Neuronal. Interact.8, 204–216 (2008). CASPubMed Google Scholar
Mosekilde, L. Primary hyperparathyroidism and the skeleton. Clin. Endocrinol. (Oxf.)69, 1–19 (2008). ArticleCAS Google Scholar
Bliuc, D. et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA301, 513–521 (2009). ArticleCASPubMed Google Scholar
Johnell, O. et al. Mortality after osteoporotic fractures. Osteoporos. Int.15, 38–42 (2004). ArticleCASPubMed Google Scholar
Holm, K. & Hedricks, C. Immobility and bone loss in the aging adult. Crit. Care Nurs. Q.12, 46–51 (1989). ArticleCASPubMed Google Scholar
Michalakis, K., Peitsidis, P. & Ilias, I. Pregnancy- and lactation-associated osteoporosis: a narrative mini-review. Endocr. Regul.45, 43–47 (2011). CASPubMed Google Scholar
Howe, T. E. et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database. Syst. Rev. CD000333 (2011).
Sinaki, M. et al. The role of exercise in the treatment of osteoporosis. Curr. Osteoporos. Rep.8, 138–144 (2010). ArticlePubMed Google Scholar
Romas, E. & Gillespie, M. T. Inflammation-induced bone loss: can it be prevented? Rheum. Dis. Clin. North Am.32, 759–773 (2006). ArticlePubMed Google Scholar
Smolen, J. S. et al. Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and TNF-blockade. Ann. Rheum. Dis.68, 823–827 (2009). ArticleCASPubMed Google Scholar
Gaur, T. et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J. Biol. Chem.280, 33132–33140 (2005). ArticleCASPubMed Google Scholar
Derynck, R. & Zhang, Y. E. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature425, 577–584 (2003). This study provides an authoritative review of the signal transduction pathways mediated bythe transforming growth factor-β protein family, to which BMPs belong, which utilize SMADs as intracellular effectors of transcriptional regulation. ArticleCASPubMed Google Scholar
Qin, L. et al. Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics. J. Biol. Chem.278, 19723–19731 (2003). ArticleCASPubMed Google Scholar
Bodine, P. V., Seestaller-Wehr, L., Kharode, Y. P., Bex, F. J. & Komm, B. S. Bone anabolic effects of parathyroid hormone are blunted by deletion of the Wnt antagonist secreted frizzled-related protein-1. J. Cell Physiol.210, 352–357 (2007). ArticleCASPubMed Google Scholar
Gazzerro, E. & Canalis, E. Bone morphogenetic proteins and their antagonists. Rev. Endocr. Metab. Disord.7, 51–65 (2006). ArticleCASPubMed Google Scholar
Franceschi, R. T. & Xiao, G. Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J. Cell Biochem.88, 446–454 (2003). ArticleCASPubMed Google Scholar
Lian, J. B. et al. Networks and hubs for the transcriptional control of osteoblastogenesis. Rev. Endocr. Metab. Disord.7, 1–16 (2006). ArticleCASPubMed Google Scholar
Yamane, T. et al. Wnt signaling regulates hemopoiesis through stromal cells. J. Immunol.167, 765–772 (2001). ArticleCASPubMed Google Scholar
Van Den Berg, D. J., Sharma, A. K., Bruno, E. & Hoffman, R. Role of members of the Wnt gene family in human hematopoiesis. Blood92, 3189–3202 (1998). CASPubMed Google Scholar
van Amerongen, R. & Nusse, R. Towards an integrated view of Wnt signaling in development. Development136, 3205–3214 (2009). ArticleCASPubMed Google Scholar
Fedi, P. et al. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. J. Biol. Chem.274, 19465–19472 (1999). ArticleCASPubMed Google Scholar
Kwack, M. H. et al. Dihydrotestosterone-inducible Dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J. Invest. Dermatol.128, 262–269 (2008). ArticleCASPubMed Google Scholar
Tian, E. et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N. Engl. J. Med.349, 2483–2494 (2003). ArticleCASPubMed Google Scholar
Diarra, D. et al. Dickkopf-1 is a master regulator of joint remodeling. Nature Med.13, 156–163 (2007). ArticleCASPubMed Google Scholar
Mao, B. et al. Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling. Nature417, 664–667 (2002). ArticleCASPubMed Google Scholar
Veverka, V. et al. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J. Biol. Chem.284, 10890–10900 (2009). ArticleCASPubMedPubMed Central Google Scholar
Romero, G. et al. Parathyroid hormone receptor directly interacts with Dishevelled to regulate β-catenin signaling and osteoclastogenesis. J. Biol. Chem.285, 14756–14763 (2010). ArticleCASPubMedPubMed Central Google Scholar
Nakashima, K. et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell108, 17–29 (2002). This publication provides the first description of the role of osterix in osteoblast differentiation. ArticleCASPubMed Google Scholar
Koga, T. et al. NFAT and osterix cooperatively regulate bone formation. Nature Med.11, 880–885 (2005). ArticleCASPubMed Google Scholar
Chang, J. et al. Inhibition of osteoblastic bone formation by nuclear factor-κB. Nature Med.15, 682–689 (2009). ArticleCASPubMed Google Scholar
Krum, S. A., Chang, J., Miranda-Carboni, G. & Wang, C. Y. Novel functions for NFκB: inhibition of bone formation. Nature Rev. Rheumatol.6, 607–611 (2010). ArticleCAS Google Scholar
Gooi, J. H. et al. Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes. Bone46, 1486–1497 (2010). ArticleCASPubMed Google Scholar
Yasuda, H. et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl Acad. Sci. USA95, 3597–3602 (1998). This was one of the initial studies describing RANKL and its pivotal osteoclastogenic role. ArticleCASPubMedPubMed Central Google Scholar
Murshed, M., Harmey, D., Millan, J. L., McKee, M. D. & Karsenty, G. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev.19, 1093–1104 (2005). ArticleCASPubMedPubMed Central Google Scholar
Bonewald, L. F. Osteocytes as dynamic multifunctional cells. Ann. NY Acad. Sci.1116, 281–290 (2007). ArticleCASPubMed Google Scholar
Schneider, P., Meier, M., Wepf, R. & Muller, R. Towards quantitative 3D imaging of the osteocyte lacuno–canalicular network. Bone47, 848–858 (2010). ArticlePubMed Google Scholar
van Bezooijen, R. L., ten Dijke, P., Papapoulos, S. E. & Lowik, C. W. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev.16, 319–327 (2005). ArticleCASPubMed Google Scholar
Murakami, M. et al. IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science260, 1808–1810 (1993). This paper clarifies the complexity of IL-6R molecules and signalling. ArticleCASPubMed Google Scholar
Rose-John, S., Scheller, J., Elson, G. & Jones, S. A. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J. Leukoc. Biol.80, 227–236 (2006). ArticleCASPubMed Google Scholar
Walker, E. C. et al. Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J. Clin. Invest.120, 582–592 (2010). ArticleCASPubMedPubMed Central Google Scholar
Malaval, L., Liu, F., Vernallis, A. B. & Aubin, J. E. GP130/OSMR is the only LIF/IL-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors. J. Cell Physiol.204, 585–593 (2005). ArticleCASPubMed Google Scholar
Sims, N. A. & Walsh, N. C. gp130 cytokines and bone remodelling in health and disease. BMB Rep.43, 513–523 (2010). ArticleCASPubMed Google Scholar
Manolagas, S. C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev.21, 115–137 (2000). CASPubMed Google Scholar
Hay, E., Lemonnier, J., Fromigue, O., Guenou, H. & Marie, P. J. Bone morphogenetic protein receptor IB signaling mediates apoptosis independently of differentiation in osteoblastic cells. J. Biol. Chem.279, 1650–1658 (2004). ArticleCASPubMed Google Scholar
Bradford, P. G., Gerace, K. V., Roland, R. L. & Chrzan, B. G. Estrogen regulation of apoptosis in osteoblasts. Physiol. Behav.99, 181–185 (2010). ArticleCASPubMed Google Scholar
Moriishi, T. et al. Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis. PLoS ONE6, e27487 (2011). ArticleCASPubMedPubMed Central Google Scholar
de Vernejoul, M. C. & Kornak, U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann. NY Acad. Sci.1192, 269–277 (2010). ArticleCASPubMed Google Scholar
Li, X. et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Miner. Res.23, 860–869 (2008). ArticlePubMed Google Scholar
Wagner, E. F. Bone development and inflammatory disease is regulated by AP-1 (Fos/Jun). Ann. Rheum. Dis.69 (Suppl. 1), 86–88 (2010). ArticleCAS Google Scholar
Schonthaler, H. B., Guinea-Viniegra, J. & Wagner, E. F. Targeting inflammation by modulating the Jun/AP-1 pathway. Ann. Rheum. Dis.70 (Suppl. 1), 109–112 (2011). ArticleCAS Google Scholar
Shaulian, E. & Karin, M. AP-1 as a regulator of cell life and death. Nature Cell Biol.4, E131–E136 (2002). ArticleCASPubMed Google Scholar
Koga, T. et al. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature428, 758–763 (2004). ArticleCASPubMed Google Scholar
Takayanagi, H. et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell3, 889–901 (2002). ArticleCASPubMed Google Scholar
Delaisse, J. M. et al. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities. Microsc. Res. Tech.61, 504–513 (2003). ArticleCASPubMed Google Scholar
Supanchart, C. & Kornak, U. Ion channels and transporters in osteoclasts. Arch. Biochem. Biophys.473, 161–165 (2008). ArticleCASPubMed Google Scholar
Goldring, S. R., Roelke, M. S., Petrison, K. K. & Bhan, A. K. Human giant cell tumors of bone identification and characterization of cell types. J. Clin. Invest.79, 483–491 (1987). ArticleCASPubMedPubMed Central Google Scholar
Hofbauer, L. C. et al. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J. Bone Miner. Res.15, 2–12 (2000). ArticleCASPubMed Google Scholar
Wiktor-Jedrzejczak, W. et al. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc. Natl Acad. Sci. USA87, 4828–4832 (1990). ArticleCASPubMedPubMed Central Google Scholar
Grigoriadis, A. E. et al. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science266, 443–448 (1994). This study reveals the essential role of the transcription factor AP1, and particularly its component FOS, in osteoclastogenesis. ArticleCASPubMed Google Scholar
Binder, N. B. et al. Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis. Nature Med.15, 417–424 (2009). ArticleCASPubMed Google Scholar
Kim, M. S., Day, C. J. & Morrison, N. A. MCP-1 is induced by receptor activator of nuclear factor-κB ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. J. Biol. Chem.280, 16163–16169 (2005). ArticleCASPubMed Google Scholar
Kong, Y. Y. et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature402, 304–309 (1999). This publication links the adaptive immune system to osteoclast activation and inflammatory bone destruction. ArticleCASPubMed Google Scholar
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. USA98, 13960–13965 (2001). This study provides evidence of the role of TNF in osteoporosis induced by oestrogen deficiency. ArticleCASPubMedPubMed Central Google Scholar
Kapinas, K., Kessler, C., Ricks, T., Gronowicz, G. & Delany, A. M. miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J. Biol. Chem.285, 25221–25231 (2010). ArticleCASPubMedPubMed Central Google Scholar
Sugatani, T. & Hruska, K. A. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J. Biol. Chem.284, 4667–4678 (2009). ArticleCASPubMedPubMed Central Google Scholar
Gough, A. K., Lilley, J., Eyre, S., Holder R. L. & Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet344, 23–27 (1994). ArticleCASPubMed Google Scholar
Romas, E. Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract. Res. Clin. Rheumatol.19, 1065–1079 (2005). ArticleCASPubMed Google Scholar
Roldan, J. F., del, Rincón, I. & Escalante, A. Loss of cortical bone from the metacarpal diaphysis in patients with rheumatoid arthritis: independent effects of systemic inflammation and glucocorticoids. J. Rheumatol.33, 508–516 (2006). PubMed Google Scholar
Gravallese, E. M. et al. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am. J. Pathol.152, 943–951 (1998). This study reveals the role of synovial-derived osteoclasts in local bone damage (erosions) in patients with rheumatoid arthritis. CASPubMedPubMed Central Google Scholar
Garcia-Carrasco, M. et al. Osteoporosis in patients with systemic lupus erythematosus. Isr. Med. Assoc. J.11, 486–491 (2009). PubMed Google Scholar
Grisar, J. et al. Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation. J. Rheumatol.29, 1430–1436 (2002). PubMed Google Scholar
Ali, T., Lam, D., Bronze, M. S. & Humphrey, M. B. Osteoporosis in inflammatory bowel disease. Am. J. Med.122, 599–604 (2009). ArticlePubMedPubMed Central Google Scholar
Paganelli, M. et al. Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease. Inflamm. Bowel Dis.13, 416–423 (2007). ArticlePubMed Google Scholar
Bianchi, M. L. & Bardella, M. T. Bone in celiac disease. Osteoporos. Int.19, 1705–1716 (2008). ArticlePubMed Google Scholar
Cashman, K. D. Altered bone metabolism in inflammatory disease: role for nutrition. Proc. Nutr. Soc.67, 196–205 (2008). ArticleCASPubMed Google Scholar
Shead, E. F., Haworth, C. S., Barker, H., Bilton, D. & Compston, J. E. Osteoclast function, bone turnover and inflammatory cytokines during infective exacerbations of cystic fibrosis. J. Cyst. Fibros.9, 93–98 (2010). ArticleCASPubMed Google Scholar
Dam, T. T., Harrison, S., Fink, H. A., Ramsdell, J. & Barrett-Connor, E. Bone mineral density and fractures in older men with chronic obstructive pulmonary disease or asthma. Osteoporos. Int.21, 1341–1349 (2010). ArticlePubMed Google Scholar
Yoshihara, A., Seida, Y., Hanada, N. & Miyazaki, H. A longitudinal study of the relationship between periodontal disease and bone mineral density in community-dwelling older adults. J. Clin. Periodontol.31, 680–684 (2004). ArticlePubMed Google Scholar
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.164, 543–555 (2004). ArticleCASPubMedPubMed Central Google Scholar
Lin, C. L., Moniz, C., Chambers, T. J. & Chow, J. W. Colitis causes bone loss in rats through suppression of bone formation. Gastroenterology111, 1263–1271 (1996). ArticleCASPubMed Google Scholar
Mattila, K. J., Valle, M. S., Nieminen, M. S., Valtonen, V. V. & Hietaniemi, K. L. Dental infections and coronary atherosclerosis. Atherosclerosis103, 205–211 (1993). ArticleCASPubMed Google Scholar
Reddy, M. S. Oral osteoporosis: is there an association between periodontitis and osteoporosis? Compend. Contin. Educ. Dent.23, 21–28 (2002). PubMed Google Scholar
Kawai, T. et al. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am. J. Pathol.169, 987–998 (2006). ArticleCASPubMedPubMed Central Google Scholar
Teng, Y. T. et al. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J. Clin. Invest.106, R59–R67 (2000). ArticleCASPubMedPubMed Central Google Scholar
Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V. K. IL-17 and Th17 cells. Annu. Rev. Immunol.27, 485–517 (2009). ArticleCASPubMed Google Scholar
Hundorfean, G., Neurath, M. F. & Mudter, J. Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease. Inflamm. Bowel Dis.18, 180–186 (2012). ArticlePubMed Google Scholar
Wong, P. K. et al. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum.54, 158–168 (2006). This study provides evidence of the role of IL-6 and associated IL-17 production on osteoclast generation. ArticleCASPubMed Google Scholar
Dinarello, C. A. Interleukin-1 and interleukin-1 antagonism. Blood77, 1627–1652 (1991). CASPubMed Google Scholar
Tracey K. J. & Cerami, A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu. Rev. Med.45, 491–503 (1994). ArticleCASPubMed Google Scholar
Dinarello, C. A. et al. Tumor necrosis factor (cachectin) is an endogeneous pyrogen and induces production of interleukin 1. J. Exp. Med.163, 1433–1450 (1986). ArticleCASPubMed Google Scholar
Naka, T., Nishimoto, N. & Kishimoto, T. The paradigm of IL-6: from basic science to medicine. Arthritis Res.4 (Suppl. 3), 233–242 (2002). Article Google Scholar
Kishimoto, T. IL-6: from its discovery to clinical applications. Int. Immunol.22, 347–352 (2010). ArticleCASPubMed Google Scholar
Wallach, D. et al. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu. Rev. Immunol.17, 331–367 (1999). ArticleCASPubMed Google Scholar
Goeddel, D. V. Signal transduction by tumor necrosis factor: the Parker B. Francis Lectureship. Chest116 (Suppl. 1), 69–73 (1999). Article Google Scholar
Sethi, G., Sung, B. & Aggarwal, B. B. TNF: a master switch for inflammation to cancer. Front. Biosci.13, 5094–5107 (2008). ArticleCASPubMed Google Scholar
Ikejima, T., Okusawa, S., Ghezzi, P., van der Meer, J. W. & Dinarello, C. A. Interleukin-1 induces tumor necrosis factor (TNF) in human peripheral blood mononuclear cells in vitro and a circulating TNF-like activity in rabbits. J. Infect. Dis.162, 215–223 (1990). ArticleCASPubMed Google Scholar
Legendre, F., Bogdanowicz, P., Boumediene, K. & Pujol, J. P. Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of transcription and mitogen-activated protein kinase/extracellular signal-related kinase in upregulation of matrix metalloproteinase and ADAMTS gene expression in articular chondrocytes. J. Rheumatol.32, 1307–1316 (2005). PubMed Google Scholar
Rowan, A. D. et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum.44, 1620–1632 (2001). ArticleCASPubMed Google Scholar
Shingu, M. et al. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin. Exp. Immunol.94, 145–149 (1993). ArticleCASPubMedPubMed Central Google Scholar
Solis-Herruzo, J. A. et al. Interleukin-6 increases rat metalloproteinase-13 gene expression through stimulation of activator protein 1 transcription factor in cultured fibroblasts. J. Biol. Chem.274, 30919–30926 (1999). ArticleCASPubMed Google Scholar
Richards, C., Gauldie, J. & Baumann, H. Cytokine control of acute phase protein expression. Eur. Cytokine Netw.2, 89–98 (1991). CASPubMed Google Scholar
Dinarello, C. A. Interleukin-1 and the pathogenesis of the acute-phase response. N. Engl. J. Med.311, 1413–1418 (1984). ArticleCASPubMed Google Scholar
Kushner, I. Regulation of the acute phase response by cytokines. Perspect. Biol. Med.36, 611–622 (1993). ArticleCASPubMed Google Scholar
Andus, T., Geiger, T., Hirano, T., Kishimoto, T. & Heinrich, P. C. Action of recombinant human interleukin 6, interleukin 1β and tumor necrosis factor α on the mRNA induction of acute-phase proteins. Eur. J. Immunol.18, 739–746 (1988). ArticleCASPubMed Google Scholar
Zhang, Y. H., Lin, J. X. & Vilcek, J. Interleukin-6 induction by tumor necrosis factor and interleukin-1 in human fibroblasts involves activation of a nuclear factor binding to a kappa B-like sequence. Mol. Cell Biol.10, 3818–3823 (1990). ArticleCASPubMedPubMed Central Google Scholar
Everaerdt, B., Brouckaert, P. & Fiers, W. Recombinant IL-1 receptor antagonist protects against TNF-induced lethality in mice. J. Immunol.152, 5041–5049 (1994). CASPubMed Google Scholar
Devlin, R. D., Reddy, S. V., Savino, R., Ciliberto, G. & Roodman G. D. IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1,25(OH)2D3, on osteoclast-like cell formation in normal human bone marrow cultures. J. Bone Miner. Res.13, 393–399 (1998). ArticleCASPubMed Google Scholar
Ma, T. et al. Human interleukin-1-induced murine osteoclastogenesis is dependent on RANKL, but independent of TNF-α. Cytokine26, 138–144 (2004). ArticleCASPubMed Google Scholar
Lee, Z. H. et al. IL-1α stimulation of osteoclast survival through the PI 3-kinase/Akt and ERK pathways. J. Biochem.131, 161–166 (2002). ArticleCASPubMed Google Scholar
Kobayashi, K. et al. Tumor necrosis factor α stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL–RANK interaction. J. Exp. Med.191, 275–286 (2000). ArticleCASPubMedPubMed Central Google Scholar
Kotake, S. et al. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J. Bone Miner. Res.11, 88–95 1996. ArticleCASPubMed Google Scholar
De Benedetti, F. et al. Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis Rheum.54, 3551–3563 (2006). ArticleCASPubMed Google Scholar
Lam, J. et al. TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin. Invest.106, 1481–1488 (2000). This report reveals the role of the pro-inflammatory cytokine TNF in osteoclastogenesis. ArticleCASPubMedPubMed Central Google Scholar
Abu-Amer, Y., Ross, F. P., Edwards, J. & Teitelbaum S. L. Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its p55 receptor. J. Clin. Invest.100, 1557–1565 (1997). ArticleCASPubMedPubMed Central Google Scholar
Bluml, S. et al. Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis. Arthritis Rheum.62, 1608–1619 (2010). This study dissects the osteoclastogenic effects of TNF signals, showing that these effects are mediated via activation of TNF receptor 1 rather than TNF receptor 2, and that the latter may have protective effects. ArticleCASPubMed Google Scholar
Zhang, Y. H., Heulsmann, A., Tondravi, M. M., Mukherjee, A. & Abu-Amer, Y. Tumor necrosis factor-α (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J. Biol. Chem.276, 563–568 (2001). ArticleCASPubMed Google Scholar
Zou, W. et al. Syk, c-Src, the αvβ3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J. Cell Biol.176, 877–888 (2007). ArticleCASPubMedPubMed Central Google Scholar
Zvaifler, N. J. Rheumatoid synovitis. An extravascular immune complex disease. Arthritis Rheum.17, 297–305 (1974). ArticleCASPubMed Google Scholar
Weissmann, G. Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases. Bull. NYU Hosp. Jt Dis.67, 251–253 (2009). PubMed Google Scholar
Brown, E. E., Edberg, J. C. & Kimberly, R. P. Fc receptor genes and the systemic lupus erythematosus diathesis. Autoimmunity40, 567–581 (2007). ArticleCASPubMed Google Scholar
Mocsai, A. et al. The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc. Natl Acad. Sci. USA101, 6158–6163 (2004). ArticleCASPubMedPubMed Central Google Scholar
Scott, D. L., Symmons, D. P., Coulton, B. L. & Popert, A. J. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet1, 1108–1111 (1987). ArticleCASPubMed Google Scholar
Aringer, M. & Smolen, J. S. Therapeutic blockade of TNF in patients with SLE — promising or crazy? Autoimmunity Rev. 18 May 2011 (doi:10.1016/j.autrev.2011.05.001.2011).
Sokolove, J., Zhao, X., Chandra, P. E. & Robinson, W. H. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum.63, 53–62 (2011). ArticleCASPubMedPubMed Central Google Scholar
Guerne, P. A., Carson, D. A. & Lotz, M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J. Immunol.144, 499–505 (1990). CASPubMed Google Scholar
van Gool, J., van Vugt, H., Helle, M. & Aarden, L. A. The relation among stress, adrenalin, interleukin 6 and acute phase proteins in the rat. Clin. Immunol. Immunopathol.57, 200–210 (1990). ArticleCASPubMed Google Scholar
Chrousos, G. P. The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation. N. Engl. J. Med.332, 1351–1362 (1995). ArticleCASPubMed Google Scholar
Perlstein, R. S., Whitnall, M. H., Abrams, J. S., Mougey, E. H. & Neta, R. Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology132, 946–952 (1993). ArticleCASPubMed Google Scholar
Rachon, D., Mysliwska, J., Suchecka-Rachon, K., Wieckiewicz, J. & Mysliwski, A. Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women. J. Endocrinol.172, 387–395 (2002). ArticleCASPubMed Google Scholar
Girasole, G., Passeri, G., Jilka, R. L. & Manolagas, S. C. Interleukin-11: a new cytokine critical for osteoclast development. J. Clin. Invest.93, 1516–1524 (1994). ArticleCASPubMedPubMed Central Google Scholar
Okamoto, H. et al. The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis Rheum.40, 1096–1105 (1997). ArticleCASPubMed Google Scholar
Sasai, M. et al. Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice. Arthritis Rheum.42, 1635–1643 (1999). ArticleCASPubMed Google Scholar
Gilbert, L. et al. Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2αA) is inhibited by tumor necrosis factor-α. J. Biol. Chem.277, 2695–2701 (2002). ArticleCASPubMed Google Scholar
Gilbert, L. C., Rubin, J. & Nanes, M. S. The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation independently of apoptosis. Am. J. Physiol. Endocrinol. Metab.288, E1011–E1018 (2005). ArticleCASPubMed Google Scholar
Kaneki, H. et al. Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. J. Biol. Chem.281, 4326–4333 (2006). ArticleCASPubMed Google Scholar
Abbas, S., Zhang, Y. H., Clohisy, J. C. & Abu-Amer, Y. Tumor necrosis factor-α inhibits pre-osteoblast differentiation through its type-1 receptor. Cytokine22, 33–41 (2003). ArticleCASPubMed Google Scholar
Mukai, T. et al. TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem. Biophys. Res. Commun.356, 1004–1010 (2007). ArticleCASPubMed Google Scholar
Ding, J. et al. TNF-α and IL-1β inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells. Life Sci.84, 499–504 (2009). ArticleCASPubMed Google Scholar
Hughes, F. J. & Howells, G. L. Interleukin-6 inhibits bone formation in vitro. Bone Miner.21, 21–28 (1993). ArticleCASPubMed Google Scholar
Hughes, F. J. & Howells, G. L. Interleukin-11 inhibits bone formation in vitro. Calcif. Tissue Int.53, 362–364 (1993). ArticleCASPubMed Google Scholar
Li, X. et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem.280, 19883–19887 (2005). ArticleCASPubMed Google Scholar
Mason, J. J. & Williams, B. O. SOST and DKK: antagonists of LRP family signaling as targets for treating bone disease. J. Osteoporos.2010, 460120 (2010). ArticleCASPubMedPubMed Central Google Scholar
Viswanathan, A. & Sylvester, F. A. Chronic pediatric inflammatory diseases: effects on bone. Rev. Endocr. Metab. Disord.9, 107–122 (2008). ArticlePubMed Google Scholar
Capriles, V. D., Martini, L. A. & Areas, J. A. Metabolic osteopathy in celiac disease: importance of a gluten-free diet. Nutr. Rev.67, 599–606 (2009). ArticlePubMed Google Scholar
Payne, J. B. & Golub, L. M. Using tetracyclines to treat osteoporotic/osteopenic bone loss: from the basic science laboratory to the clinic. Pharmacol. Res.63, 121–129 (2011). ArticleCASPubMed Google Scholar
Elborn, J. S. How can we prevent multisystem complications of cystic fibrosis? Semin. Respir. Crit. Care Med.28, 303–311 (2007). ArticlePubMed Google Scholar
Haugeberg, G., Conaghan, P. G., Quinn, M. & Emery, P. Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann. Rheum. Dis.68, 1898–1901 (2009). ArticleCASPubMed Google Scholar
Strand, V. & Simon, L. S. Low dose glucocorticoids in early rheumatoid arthritis. Clin. Exp. Rheumatol.21 (Suppl. 31), 186–190 (2003). Google Scholar
Hoes, J. N. et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann. Rheum. Dis.66, 1560–1567 (2007). ArticleCASPubMedPubMed Central Google Scholar
Teitelbaum, S. L., Seton, M. P. & Saag, K. G. Should bisphosphonates be used for long-term treatment of glucocorticoid-induced osteoporosis? Arthritis Rheum.63, 325–328 (2011). ArticleCASPubMedPubMed Central Google Scholar
Lange, U., Teichmann, J., Muller-Ladner, U. & Strunk, J. Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-α antibody: a prospective open-label pilot study. Rheumatology (Oxford)44, 1546–1548 (2005). ArticleCAS Google Scholar
Bernstein, M., Irwin, S. & Greenberg, G. R. Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease. Am. J. Gastroenterol.100, 2031–2035 (2005). ArticleCASPubMed Google Scholar
Veerappan, S. G., O'Morain, C. A., Daly, J. S. & Ryan, B. M. Review article: the effects of antitumour necrosis factor-a on bone metabolism in inflammatory bowel disease. Aliment. Pharmacol. Ther.33, 1261–1272 (2011). ArticleCASPubMed Google Scholar
Kremer, J. M. et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum.63, 609–621 (2011). ArticleCASPubMed Google Scholar
Ito, H. et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology126, 989–996 (2004). ArticleCASPubMed Google Scholar
Hsu, B., Zhou, B., Smolen, J. S. & Weinblatt, M. Proof-of-concept for CNTO 136, a human anti-interleukin-6 monoclonal antibody, in a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann. Rheum. Dis.70 (Suppl. 3), 459 (2011). Google Scholar
Mease, P. et al. Inhibition of IL-6 with ALD518 improves disease activity in rheumatoid arthritis in a randomized, double-blind, placebo-controlled, dose ranging Phase 2 clinical trial. Ann. Rheum. Dis.69 (Suppl. 3), 98 (2011). Google Scholar
Hickling, M., Golor, G., Juillon, A., Shaw, S. & Kretsos, K. Safety and pharmacokinetics of CDP6038, an anti-IL-6 monoclonal antibody, administered by subcutaneous injection and intravenous infusion to healthy male volunteers: a Phase 1 study. Ann. Rheum. Dis.70 (Suppl. 3), 471 (2011). Google Scholar
Nam, J. L. et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann. Rheum. Dis.69, 976–986 (2010). ArticleCASPubMed Google Scholar
Baltzer, A. W. et al. Gene therapy for osteoporosis: evaluation in a murine ovariectomy model. Gene Ther.8, 1770–1776 (2001). ArticleCASPubMed Google Scholar
Genovese, M. et al. Secukinumab (ain457) showed a rapid decrease of disease activity in patients with active rheumatoid arthritis including those with high inflammatory burden. Ann. Rheum. Dis.70 (Suppl. 3), 472 (2011). Google Scholar
Bluml, S. et al. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum.63, 1281–1288 (2011). ArticleCASPubMed Google Scholar
Yang, M. & Mattes, J. Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol. Ther.117, 94–104 (2008). ArticleCASPubMed Google Scholar
Smolen J. S. & Steiner, G. Therapeutic strategies for rheumatoid arthritis. Nature Rev. Drug Discov.2, 473–488 (2003). ArticleCAS Google Scholar
Westhovens, R. et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann. Rheum. Dis.68, 1870–1877 (2009). ArticleCASPubMed Google Scholar
Tak, P. P. et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann. Rheum. Dis.70, 39–46 (2011). ArticleCASPubMed Google Scholar
Hein, G. et al. Influence of rituximab on markers of bone remodeling in patients with rheumatoid arthritis: a prospective open-label pilot study. Rheumatol Int.31, 269–272 (2011). ArticleCASPubMed Google Scholar
van der Heijde, D. et al. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, in combination with methotrexate reduced the progression of structural damage in patients with rheumatoid arthritis: a 24-month Phase 3 study. [meeting abstract] Arthritis Rheum.63 (Suppl. 10), 2592 (2011). Google Scholar
Weinblatt, M. E. et al. An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N. Engl. J. Med.363, 1303–1312 (2010). ArticleCASPubMed Google Scholar
Massey, D. C., Bredin, F. & Parkes, M. Use of sirolimus (rapamycin) to treat refractory Crohn's disease. Gut57, 1294–1296 (2008). ArticleCASPubMed Google Scholar
Cejka, D. et al. Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis. Arthritis Rheum.62, 2294–2302 (2010). ArticleCASPubMed Google Scholar
Westenfeld, R. et al. Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis —implications for post-transplantation bone disease. Nephrol. Dial. Transplant.12, 4115–4123 (2011). ArticleCAS Google Scholar
Dobashi, Y., Watanabe, Y., Miwa, C., Suzuki, S. & Koyama, S. Mammalian target of rapamycin: a central node of complex signaling cascades. Int. J. Clin. Exp. Pathol.4, 476–495 (2011). CASPubMedPubMed Central Google Scholar
Markman, B., Dienstmann, R. & Tabernero, J. Targeting the PI3K/Akt/mTOR pathway — beyond rapalogs. Oncotarget1, 530–543 (2010). PubMedPubMed Central Google Scholar
Kim, J. E. & Chen, J. Regulation of peroxisome proliferator-activated receptor-γ activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes53, 2748–2756 (2004). ArticleCASPubMed Google Scholar
Glantschnig, H., Fisher, J. E., Wesolowski, G., Rodan, G. A. & Reszka, A. A. M-CSF, TNFα and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death. Differ.10, 1165–1177 (2003). ArticleCASPubMed Google Scholar
Garrett, I. R. et al. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J. Clin. Invest.111, 1771–1782 (2003). ArticleCASPubMedPubMed Central Google Scholar
Chen, D., Frezza, M., Schmitt, S., Kanwar, J. & Dou, P. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr. Cancer Drug Targets11, 239–253 (2011). ArticleCASPubMedPubMed Central Google Scholar
von Metzler, I. et al. Bortezomib inhibits human osteoclastogenesis. Leukemia21, 2025–2034 (2007). ArticleCASPubMed Google Scholar
Zavrski, I. et al. Proteasome inhibitors abrogate osteoclast differentiation and osteoclast function. Biochem. Biophys. Res. Commun.333, 200–205 (2005). ArticleCASPubMed Google Scholar
Hongming, H. & Jian, H. Bortezomib inhibits maturation and function of osteoclasts from PBMCs of patients with multiple myeloma by downregulating TRAF6. Leuk. Res.33, 115–122 (2009). ArticleCASPubMed Google Scholar
Schmidt, N. et al. Targeting the proteasome: partial inhibition of the proteasome by bortezomib or deletion of the immunosubunit LMP7 attenuates experimental colitis. Gut59, 896–906 (2010). ArticleCASPubMed Google Scholar
Lee, S. W., Kim, J. H., Park, Y. B. & Lee, S. K. Bortezomib attenuates murine collagen-induced arthritis. Ann. Rheum. Dis.68, 1761–1767 (2009). ArticleCASPubMed Google Scholar
Yannaki, E. et al. The proteasome inhibitor bortezomib drastically affects inflammation and bone disease in adjuvant-induced arthritis in rats. Arthritis Rheum.62, 3277–3288 (2010). ArticleCASPubMed Google Scholar
Lin, C. L., Moniz, C. & Chow, J. W. Treatment with fluoride or bisphosphonates prevents bone loss associated with colitis in the rat. Calcif. Tissue Int.67, 373–377 (2000). ArticleCASPubMed Google Scholar
Eggelmeijer, F. et al. Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial. Arthritis Rheum.39, 396–402 (1996). ArticleCASPubMed Google Scholar
Kwak, H. B. et al. Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss. Biol. Pharm. Bull.32, 1193–1198 (2009). ArticleCASPubMed Google Scholar
Watts, N. B. & Diab, D. L. Long-term use of bisphosphonates in osteoporosis. J. Clin. Endocrinol. Metab.95, 1555–1565 (2010). ArticleCASPubMed Google Scholar
McClung, M. R. et al. Denosumab in postmenopausal women with low bone mineral density. N. Engl. J. Med.354, 821–831 (2006). ArticleCASPubMed Google Scholar
Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med.361, 756–765 (2009). ArticleCASPubMed Google Scholar
Cohen, S. B. et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, Phase II clinical trial. Arthritis Rheum.58, 1299–1309 (2008). The results from this trial provide proof of concept that selectively targeting osteoclasts prevents local inflammatory bone loss but does not affect inflammation or cartilage damage. ArticleCASPubMed Google Scholar
Dore, R. K. et al. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann. Rheum. Dis.69, 872–875 (2010). ArticleCASPubMed Google Scholar
Adler, R. A. & Gill, R. S. Clinical utility of denosumab for treatment of bone loss in men and women. Clin. Interv. Aging6, 119–124 (2011). ArticleCASPubMedPubMed Central Google Scholar
Saad, F. et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled Phase III trials in cancer patients with bone metastases. Ann. Oncol. 10 Oct 2011 (doi:10.1093/annonc/mdr435).
Takahata, M., Awad, H. A., O'Keefe, R. J., Bukata, S. V. & Schwarz, E. M. Endogenous tissue engineering: PTH therapy for skeletal repair. Cell Tissue Res. 31 May 2011 (doi:10.1007/s00441-011-1188-4).
Vincent, C. et al. Pro-inflammatory cytokines TNF-related weak inducer of apoptosis (TWEAK) and TNFα induce the mitogen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts. J. Bone Miner. Res.24, 1434–1449 (2009). ArticleCASPubMed Google Scholar
Heiland, G. R. et al. Neutralisation of Dkk-1 protects from systemic bone loss during inflammation and reduces sclerostin expression. Ann. Rheum. Dis.69, 2152–2159 (2010). This study reveals the efficacy of blocking DKK1 on inflammatory bone loss in an experimental model. ArticleCASPubMed Google Scholar
Betts, A. M. et al. The application of target information and preclinical pharmacokinetic/pharmacodynamic modeling in predicting clinical doses of a Dickkopf-1 antibody for osteoporosis. J. Pharmacol. Exp. Ther.333, 2–13 (2010). ArticleCASPubMed Google Scholar
Ominsky, M. S. et al. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J. Bone Miner. Res.26, 1012–1021 (2011). ArticleCASPubMed Google Scholar
Tian, X. et al. Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats. Bone47, 529–533 (2010). ArticleCASPubMed Google Scholar
Li, X. et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J. Bone Miner. Res.24, 578–588 (2009). ArticleCASPubMed Google Scholar
Rickels, M. R., Zhang, X., Mumm, S. & Whyte, M. P. Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation. J. Bone Miner. Res.20, 878–885 (2005). ArticleCASPubMed Google Scholar
Zeckey, C., Hildebrand, F., Frink, M. & Krettek, C. Heterotopic ossifications following implant surgery — epidemiology, therapeutical approaches and current concepts. Semin. Immunopathol.33, 273–286 (2011). ArticlePubMed Google Scholar
Boraiah, S., Paul, O., Hawkes, D., Wickham, M. & Lorich, D. G. Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report. Clin. Orthop. Relat. Res.467, 3257–3262 (2009). ArticlePubMedPubMed Central Google Scholar
Balemans, W., Cleiren, E., Siebers, U., Horst, J. & Van Hul, W. A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene. Bone36, 943–947 (2005). ArticleCASPubMed Google Scholar
Hoff, M. et al. Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: subanalysis of the PREMIER study. BMC Musculoskelet. Disord.12, 54 (2011). ArticleCASPubMedPubMed Central Google Scholar
Eklund, S. A. & Burt, B. A. Risk factors for total tooth loss in the United States; longitudinal analysis of national data. J. Public Health Dent.54, 5–14 (1994). ArticleCASPubMed Google Scholar
Gladman, D. D. et al. Consensus on a core set of domains for psoriatic arthritis. J. Rheumatol.34, 1167–1170 (2007). PubMed Google Scholar
van der Heijde, D. et al. How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum.47, 215–218 (2002). ArticlePubMed Google Scholar
Smolen, J. S., Aletaha, D., Koeller, M., Weisman, M. & Emery, P. New therapies for the treatment of rheumatoid arthritis. Lancet370, 1861–1874 (2007). ArticleCASPubMed Google Scholar
Smolen, J. S. et al. Evidence of radiographic benefit of infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of the ATTRACT trial. Arthritis Rheum.52, 1020–1030 (2005). ArticleCASPubMed Google Scholar
Smolen, J. S. et al. The need for prognosticators in rheumatoid arthritis. Biological and clinical markers — where are we now? Arthritis Res. Ther.10, 208 (2008). ArticleCASPubMedPubMed Central Google Scholar
Smolen, J. S., Martinez-Avila, J. C. & Aletaha, D. Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its antiinflammatory effects: disassociation of the link between inflammation and destruction. Ann. Rheum. Dis. 25 Nov 2011 (doi:10.1136/annrheumdis-2011-200395).
Mattes, J., Yang, M. & Foster, P. S. Regulation of microRNA by antagomirs: a new class of pharmacological antagonists for the specific regulation of gene function? Am. J. Respir. Cell. Mol. Biol.36, 8–12 (2007). ArticleCASPubMed Google Scholar
Sims, N. A. et al. Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis Rheum.50, 2338–2346 (2004). ArticleCASPubMed Google Scholar
Herrak, P. et al. Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-mediated arthritis. Arthritis Rheum.50, 2327–2337 (2004). ArticleCASPubMed Google Scholar
Jarrett, S. J. et al. Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in early rheumatoid arthritis. Arthritis Rheum.54, 1410–1414 (2006). ArticleCASPubMed Google Scholar
Schett, G. et al. Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheum.48, 2042–2051 (2003). ArticleCASPubMed Google Scholar
Schett, G. et al. Additive bone-protective effects of anabolic treatment when used in conjunction with RANKL and tumor necrosis factor inhibition in two rat arthritis models. Arthritis Rheum.52, 1604–1611 (2005). ArticleCASPubMed Google Scholar
Aletaha, D., Funovits, J. & Smolen, J. S. Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction. Ann. Rheum. Dis.70, 733–739 (2011). ArticlePubMed Google Scholar
van der Heijde, D. et al. Expert agreement confirms that negative changes in hand and foot radiographs are a surrogate for repair in patients with rheumatoid arthritis. Arthritis Res. Ther.9, R62 (2007). ArticlePubMedPubMed Central Google Scholar
Machold, K. P. et al. Very recent onset arthritis — clinical, laboratory and radiological findings during the first year of disease. J. Rheumatol.29, 2278–2287 (2002). PubMed Google Scholar
Plant, M. J., Jones, P. W., Saklatvala, J., Ollier, W. E. & Dawes, P. T. Patterns of radiological progression in rheumatoid arthritis: results of an 8 year prospective study. J. Rheumatol.25, 417–426 (1998). CASPubMed Google Scholar
Van der Heijde, D. M. Joint erosions and patients with early rheumatoid arthritis. Br. J. Rheumatol.34,(Suppl. 2), 74–78 (1995). ArticlePubMed Google Scholar
Redlich, K. et al. Tumor necrosis factor α-mediated joint destruction is inhibited by targeting osteoclasts with osteoprotegerin. Arthritis Rheum.46, 785–792 (2002). ArticleCASPubMed Google Scholar
Muller-Ladner, U. et al. Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am. J. Pathol.149, 1607–1615 (1996). CASPubMedPubMed Central Google Scholar
Colucci, S. et al. Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFα, and IL-7 in an in vitro model derived from human psoriatic arthritis. J. Pathol.212, 47–55 (2007). ArticleCASPubMed Google Scholar
Partsch, G. et al. Highly increased levels of tumor necrosis factor-α and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J. Rheumatol.24, 518–523 (1997). CASPubMed Google Scholar
Gortz, B. et al. Arthritis induces lymphocytic bone marrow inflammation and endosteal bone formation. J. Bone Miner. Res.19, 990–998 (2004). ArticleCASPubMed Google Scholar
Jimenez-Boj, E. et al. Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum.56, 1118–1124 (2007). ArticlePubMed Google Scholar
Arnett, F. C. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum.31, 315–324 (1988). ArticleCASPubMed Google Scholar
Shimizu, S., Shiozawa, S., Shiozawa, K., Imura, S. & Fujita, T. Quantitative histologic studies on the pathogenesis of periarticular osteoporosis in rheumatoid arthritis. Arthritis Rheum.28, 25–31 (1985). ArticleCASPubMed Google Scholar
Mansson, B., Gulfe, A., Geborek, P., Heinegard, D. & Saxne, T. Release of cartilage and bone macromolecules into synovial fluid: differences between psoriatic arthritis and rheumatoid arthritis. Ann. Rheum. Dis.60, 27–31 (2001). ArticleCASPubMedPubMed Central Google Scholar
Furie, R. et al. A Phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum.63, 3918–3930 (2011). ArticleCASPubMedPubMed Central Google Scholar
Hsu, B., Sheng, S., Smolen, J. & Weinblatt, M. Results from a 2-part, proof-of-concept, dose-ranging, randomized, double-blind, placebo-controlled, Phase 2 study of sirukumab, a human anti-interleukin-6 monoclonal antibody, in active rheumatoid arthritis patients despite methotrexate therapy. [meeting abstract] Arthritis Rheum.63 (Suppl. 10), 2631 (2011). Google Scholar
Griffiths, C. E. et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N. Engl. J. Med.362, 118–128 (2010). ArticleCASPubMed Google Scholar
Taylor, P. C. et al. Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial. Ann. Rheum. Dis.70, 2119–2125 (2011). ArticleCASPubMed Google Scholar
van Vollenhoven, R. F., Kinnman, N., Vincent, E., Wax, S. & Bathon, J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a Phase II, randomized, placebo-controlled trial. Arthritis Rheum.63, 1782–1792 (2011). ArticleCASPubMed Google Scholar
Cusick, T. et al. Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey. J Bone Miner. Res. 23 Nov 2011 (doi:10.1002/jbmr.1477).
Eisman, J. A. et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J. Bone Miner. Res.26, 242–251 (2011). ArticleCASPubMed Google Scholar