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Endocrine
Erschienen in: Endocrine 1/2012

01.02.2012 | New Horizons in

New understanding and treatments for osteoporosis

verfasst von: G. Mazziotti, J. Bilezikian, E. Canalis, D. Cocchi, A. Giustina

Erschienen in: Endocrine | Ausgabe 1/2012

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Abstract

To summarize promising areas of investigation in osteoporosis and to stimulate further research in this area, as discussed in a recent international conference. Over the recent years, there has been an improvement in the knowledge of molecular pathways involved in bone formation and resorption with the development of new drugs to treat osteoporosis. Intact parathyroid hormone, teriparatide, and anti-sclerostin monoclonal antibody are anabolic drugs, whereas denosumab and odanacatib are anti-resorptive drugs with more reversible effects as compared to bisphosphonates. Anabolic and anti-resorptive agents have different effects on bone, and research in this area includes the efficacy of combination and sequential therapies with them. New insights in the molecular pathways of bone remodeling have clarified the mechanisms responsible for skeletal fragility in several forms of secondary osteoporosis, such as that occurring in type 2 diabetes, following drug exposure and systemic inflammatory diseases. Future research is needed to address the efficacy of anti-osteoporotic drugs in these more recently recognized conditions of skeletal fragility. Osteoporosis continues to be an important field of biomedical research.
Literatur
1.
E.A. Chrischilles, C.D. Butler, C.S. Davis, R.B. Wallace, A model of lifetime osteoporosis impact. Arch. Intern. Med. 51, 2026–2032 (1991)CrossRef
2.
3.
M. Almeida, L. Han, E. Ambrogini, S.M. Bartell, S.C. Manolagas, Oxidative stress stimulates apoptosis and activates NF-kappaB in osteoblastic cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol. Endocrinol. 24, 2030–2037 (2010)PubMedCrossRef
4.
E. Ambrogini, M. Almeida, M. Martin-Millan, J.H. Paik, R.A. Depinho, L. Han, J. Goellner, R.S. Weinstein, R.L. Jilka, C.A. O’Brien, S.C. Manolagas, FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab. 11, 136–146 (2010)PubMedCrossRef
5.
S.C. Manolagas, De-fense! De-fense! De-fense: scavenging H2O2 while making cholesterol. Endocrinology 149, 3264–3266 (2008)PubMedCrossRef
6.
M. Almeida, M. Martin-Millan, E. Ambrogini III, R. Bradsher, L. Han, X.D. Chen, P.K. Roberson, R.S. Weinstein, C.A. O’Brien, R.L. Jilka, S.C. Manolagas, Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA-binding-independent actions of the ERalpha. J. Bone Miner. Res. 25, 769–781 (2010)PubMed
7.
S.C. Manolagas, From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr. Rev. 31, 266–300 (2010)PubMedCrossRef
8.
9.
Y. Nam, P. Sliz, L. Song, J.C. Aster, S.C. Blacklow, Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell 124, 973–983 (2006)PubMedCrossRef
10.
V. Deregowski, E. Gazzerro, L. Priest, S. Rydziel, E. Canalis, Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-Catenin but not bone morphogenetic protein signaling. J. Biol. Chem. 281, 6203–6210 (2006)PubMedCrossRef
11.
S. Zanotti, A. Smerdel-Ramoya, L. Stadmeyer, D. Durant, F. Radtke, E. Canalis, Notch inhibits osteoblast differentiation and causes osteopenia. Endocrinology 149, 3890–3899 (2008)PubMedCrossRef
12.
M.J. Hilton, X. Tu, X. Wu, S. Bai, H. Zhao, T. Kobayashi, H.M. Kronenberg, S.L. Teitelbaum, F.P. Ross, R. Kopan, F. Long, Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat. Med. 14, 306–314 (2008)PubMedCrossRef
13.
N. Sethi, X. Dai, C.G. Winter, J. Kang, Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19, 192–205 (2011)PubMedCrossRef
14.
J. Tao, A. Erez, B. Lee, One NOTCH further: Jagged 1 in bone metastasis. Cancer Cell 19, 159–161 (2011)PubMedCrossRef
15.
S. Zanotti, A. Smerdel-Ramoya, E. Canalis, Reciprocal regulation of Notch and nuclear factor of activated T-cells (NFAT) c1 transactivation in osteoblasts. J. Biol. Chem. 286, 4576–4588 (2011)PubMedCrossRef
16.
B. Isidor, P. Lindenbaum, O. Pichon, S. Bézieau, C. Dina, S. Jacquemont, D. Martin-Coignard, C. Thauvin-Robinet, M. Le Merrer, J.L. Mandel, A. David, L. Faivre, V. Cormier-Daire, R. Redon, C. Le Caignec, Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat. Genet. 43, 306–308 (2011)PubMedCrossRef
17.
M.A. Simpson, M.D. Irving, E. Asilmaz, M.J. Gray, D. Dafou, F.V. Elmslie, S. Mansour, S.E. Holder, C.E. Brain, B.K. Burton, K.H. Kim, R.M. Pauli, S. Aftimos, H. Stewart, C.A. Kim, M. Holder-Espinasse, S.P. Robertson, W.M. Drake, R.C. Trembath, Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat. Genet. 43, 303–305 (2011)PubMedCrossRef
18.
M.M. Dvorak, A. Siddiqua, D.T. Ward, D.H. Carter, S.L. Dallas, E.F. Nemeth, D. Riccardi, Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc. Natl Acad. Sci. USA 101, 5140–5145 (2004)PubMedCrossRef
19.
N. Chattopadhyay, S. Yano, J. Tfelt-Hansen, P. Rooney, D. Kanuparthi, S. Bandyopadhyay, X. Ren, E. Terwilliger, E.M. Brown, Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts. Endocrinology 145, 3451–3462 (2004)PubMedCrossRef
20.
T. Kameda, H. Mano, Y. Yamada, H. Takai, N. Amizuka, M. Kobori, N. Izumi, H. Kawashima, H. Ozawa, K. Ikeda, A. Kameda, Y. Hakeda, M. Kumegawa, Calcium-sensing receptor in mature osteoclasts, which are bone resorbing cells. Biochem. Biophys. Res. Commun. 245, 419–422 (1998)PubMedCrossRef
21.
E.M. Brown, R.J. MacLeod, Extracellular calcium sensing and extracellular calcium signaling. Physiol. Rev. 81, 239–297 (2001)PubMed
22.
K. Ballen, Targeting the stem cell niche: squeezing blood from bones. Bone Marrow Transplant. 39, 655–660 (2007)PubMedCrossRef
23.
24.
P.J. Marie, The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone 46, 571–576 (2010)PubMedCrossRef
25.
E. Canalis, A. Giustina, J.P. Bilezikian, Mechanisms of anabolic therapies for osteoporosis. N. Engl. J. Med. 357, 905–916 (2007)PubMedCrossRef
26.
R. Pacifici, T cells: critical bone regulators in health and disease. Bone 47, 461–471 (2010)PubMedCrossRef
27.
Y. Gao, X. Wu, M. Terauchi, F. Grassi, S. Galley, X. Yang, M.N. Weitzmann, R. Pacifici, T cells potentiate PTH-induced cortical bone loss through CD40L signaling. Cell Metab. 8, 132–145 (2008)PubMedCrossRef
28.
H. Tawfeek, B. Bedi, J.Y. Li, J. Adams, T. Kobayashi, M.N. Weitzmann, H.M. Kronenberg, R. Pacifici, Disruption of PTH receptor 1 in T cells protects against PTH-induced bone loss. PLoS ONE 5, e12290 (2010)PubMedCrossRef
29.
R.M. Neer, C.D. Arnaud, J.R. Zanchetta, R. Prince, G.A. Gaich, J.Y. Reginster, A.B. Hodsman, E.F. Eriksen, S. Ish-Shalom, H.K. Genant, O. Wang, B.H. Mitlak, Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434–1441 (2001)PubMedCrossRef
30.
S.L. Greenspan, H.G. Bone, M.P. Ettinger, D.A. Hanley, R. Lindsay, J.R. Zanchetta, C.M. Blosch, A.L. Mathisen, S.A. Morris, T.B. Marriott, Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann. Intern. Med. 146, 326–339 (2007)PubMed
31.
J.P. Bilezikian, Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr. Osteoporos. Rep. 6, 24–30 (2008)PubMedCrossRef
32.
K.G. Saag, E. Shane, S. Boonen, F. Marín, D.W. Donley, K.A. Taylor, G.P. Dalsky, R. Marcus, Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N. Engl. J. Med. 357, 2028–2039 (2007)PubMedCrossRef
33.
K.G. Saag, J.R. Zanchetta, J.P. Devogelaer, R.A. Adler, R. Eastell, K. See, J.H. Krege, K. Krohn, M.R. Warner, Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum. 60, 3346–3355 (2009)PubMedCrossRef
34.
F. Cosman, R.A. Wermers, C. Recknor, K.F. Mauck, L. Xie, E.V. Glass, J.H. Krege, Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronte or raloxifene: differences between stopping and continuing the antiresorptive agent. J. Clin. Endocrinol. Metab. 94, 3772–3780 (2009)PubMedCrossRef
35.
J.S. Finkelstein, J.J. Wyland, B.Z. Leder, S.M. Burnett-Bowie, H. Lee, H. Jüppner, R.M. Neer, Effects of teriparatide retreatment in osteoporotic men and women. J. Clin. Endocrinol. Metab. 94, 2495–2501 (2009)PubMedCrossRef
36.
N.E. Cusano, J.P. Bilezikian, Teriparatide: variations on the theme of a 2-year therapeutic course. BoneKey 7, 84–87 (2010)CrossRef
37.
N.E. Cusano, J.P. Bilezikian, Combination antiresorptive and osteoanabolic therapy for osteoporosis: we are not there yet. Curr. Med. Res. Opin. (2011) [Epub ahead of print, PMID 21740288]
38.
J. Compston, The use of combination therapy in the treatment of postmenopausal osteoporosis. Endocrine (2011) [Epub ahead of print]
39.
S. Boonen, K. Milison, E. Gielen, D. Vanderschueren, Sequential therapy in the treatment of osteoporosis. Curr. Med. Res. Opin. 27, 1149–1155 (2011)PubMedCrossRef
40.
D.M. Black, S.L. Greenspan, K.E. Ensrud, L. Palermo, J.A. McGowan, T.F. Lang, P. Garnero, M.L. Bouxsein, J.P. Bilezikian, C.J. Rosen, The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N. Engl. J. Med. 349, 1207–1215 (2003)PubMedCrossRef
41.
F. Cosman, E.F. Eriksen, C. Recknor, P.D. Miller, N. Guañabens, C. Kasperk, P. Papanastasiou, A. Readie, H. Rao, J.A. Gasser, C. Bucci-Rechtweg, S. Boonen, Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis. J. Bone Miner. Res. 26, 503–511 (2011)PubMedCrossRef
42.
J.P. Bilezikian, A. Khan, J.T. Potts Jr., M.L. Brandi, B.L. Clarke, D. Shoback, H. Jüppner, P. D’Amour, J. Fox, L. Rejnmark, L. Mosekilde, M.R. Rubin, D. Dempster, R. Gafni, M.T. Collins, J. Sliney, J. Sanders, Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target organ involvement, treatment, and challenges for future research. J. Bone Miner. Res. (2011). doi: 10.​1002/​jbmr.​483. [Epub ahead of print]
43.
K.K. Winer, N. Sinaii, J. Reynolds, D. Peterson, K. Dowdy, G.B. Cutler Jr, Long term therapy of 12 children with chronic hypoparathyroidism: a randomized trail comparing synthetic human parathyroid hormone (1–34) vs calcitriol and calcium. J. Clin. Endocrinol. Metab. 95, 2680–2688 (2010)PubMedCrossRef
44.
M.R. Rubin, J.P. Bilezikian, Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement. Braz. Arch. Endocrinol. Metab. 54, 220–226 (2010)CrossRef
45.
T. Sikjaer, L. Rejnmark, L. Rolighed, L. Heickendorff, L. Mosekilde, The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism–A randomized, placebo-controlled study. J. Bone Miner. Res. 26, 2358–2370 (2011)PubMedCrossRef
46.
W.J. Boyle, W.S. Simonet, D.L. Lacey, Osteoclast differentiation and activation. Nature 423, 337–342 (2003)PubMedCrossRef
47.
W.S. Simonet, D.L. Lacey, C.R. Dunstan, M. Kelley, M.S. Chang, R. Lüthy, H.Q. Nguyen, S. Wooden, L. Bennett, T. Boone, G. Shimamoto, M. DeRose, R. Elliott, A. Colombero, H.L. Tan, G. Trail, J. Sullivan, E. Davy, N. Bucay, L. Renshaw-Gegg, T.M. Hughes, D. Hill, W. Pattison, P. Campbell, S. Sander, G. Van, J. Tarpley, P. Derby, R. Lee, W.J. Boyle, Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309–319 (1997)PubMedCrossRef
48.
N. Bucay, I. Sarosi, C.R. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H.L. Tan, W. Xu, D.L. Lacey, W.J. Boyle, W.S. Simonet, Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12, 1260–1268 (1998)PubMedCrossRef
49.
L.C. Hofbauer, C.A. Kühne, V. Viereck, The OPG/RANKL/RANK system in metabolic bone diseases. J. Musculoskelet. Neuronal Interact. 4, 268–275 (2004)PubMed
50.
P.J. Kostenuik, C. Capparelli, S. Morony, S. Adamu, G. Shimamoto, V. Shen, D.L. Lacey, C.R. Dunstan, OPG and PTH-(1–34) have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats. Endocrinology 142, 4295–4304 (2001)PubMedCrossRef
51.
P.J. Bekker, D. Holloway, A. Nakanishi, M. Arrighi, P.T. Leese, C.R. Dunstan, The effect of a single dose of osteoprotegerin in postmenopausal women. J. Bone Miner. Res. 16, 348–360 (2001)PubMedCrossRef
52.
P.J. Bekker, D.L. Holloway, A.S. Rasmussen, R. Murphy, S.W. Martin, P.T. Leese, G.B. Holmes, C.R. Dunstan, A.M. DePaoli, A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J. Bone Miner. Res. 19, 1059–1066 (2004)PubMedCrossRef
53.
H.G. Bone, M.A. Bolognese, C.K. Yuen, D.L. Kendler, P.D. Miller, Y.C. Yang, L. Grazette, J. San Martin, J.C. Gallagher, Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J. Clin. Endocrinol. Metab. 96, 972–980 (2011)PubMedCrossRef
54.
T.D. Rachner, S. Khosla, L.C. Hofbauer, Osteoporosis: now and the future. Lancet 377, 1276–1287 (2011)PubMedCrossRef
55.
S.R. Cummings, J. San Martin, M.R. McClung, E.S. Siris, R. Eastell, I.R. Reid, P. Delmas, H.B. Zoog, M. Austin, A. Wang, S. Kutilek, S. Adami, J. Zanchetta, C. Libanati, S. Siddhanti, C. Christiansen, Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 361, 756–765 (2009)PubMedCrossRef
56.
S. Boonen, J.D. Adachi, Z. Man, S.R. Cummings, K. Lippuner, O. Törring, J.C. Gallagher, J. Farrerons, A. Wang, N. Franchimont, J. San Martin, A. Grauer, M. McClung, Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J. Clin. Endocrinol. Metab. 96, 1727–1736 (2011)PubMedCrossRef
57.
C. von Keyserlingk, R. Hopkins, A. Anastasilakis, K. Toulis, R. Goeree, J.E. Tarride, F. Xie, Clinical efficacy and safety of Denosumab in postmenopausal women with low bone mineral density and osteoporosis: a meta-analysis. Semin. Arthritis Rheum. 41, 178–186 (2011)CrossRef
58.
G. Mazziotti, E. Canalis, A. Giustina, Drug-induced osteoporosis: mechanisms and clinical implications. Am. J. Med. 123, 877–884 (2010)PubMedCrossRef
59.
M.R. Smith, B. Egerdie, N. Hernández Toriz, R. Feldman, T.L. Tammela, F. Saad, J. Heracek, M. Szwedowski, C. Ke, A. Kupic, B.Z. Leder, C. Goessl, Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N. Engl. J. Med. 361, 745–755 (2009)PubMedCrossRef
60.
G.K. Ellis, H.G. Bone, R. Chlebowski, D. Paul, S. Spadafora, J. Smith, M. Fan, S. Jun, Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J. Clin. Oncol. 26, 4875–4882 (2008)PubMedCrossRef
61.
O. Sezer, U. Heider, I. Zavrski, C.A. Kühne, L.C. Hofbauer, RANK ligand and osteoprotegerin in myeloma bone disease. Blood 101, 2094–2098 (2003)PubMedCrossRef
62.
U. Heider, C. Langelotz, C. Jakob, I. Zavrski, C. Fleissner, J. Eucker, K. Possinger, L.C. Hofbauer, O. Sezer, Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Clin. Cancer Res. 9, 1436–1440 (2003)PubMed
63.
S. Roux, V. Meignin, J. Quillard, G. Meduri, A. Guiochon-Mantel, J.P. Fermand, E. Milgrom, X. Mariette, RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma. Br. J. Haematol. 117, 86–92 (2002)PubMedCrossRef
64.
N. Giuliani, S. Colla, R. Sala, M. Moroni, M. Lazzaretti, S. La Monica, S. Bonomini, M. Hojden, G. Sammarelli, S. Barillè, R. Bataille, V. Rizzoli, Human myeloma cells stimulate the receptor activator of NF-kappaB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100, 4615–4621 (2002)PubMedCrossRef
65.
66.
A.T. Stopeck, A. Lipton, J.J. Body, G.G. Steger, K. Tonkin, R.H. de Boer, M. Lichinitser, Y. Fujiwara, D.A. Yardley, M. Viniegra, M. Fan, Q. Jiang, R. Dansey, S. Jun, A. Braun, Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J. Clin. Oncol. 28, 5132–5139 (2010)PubMedCrossRef
67.
K. Fizazi, M. Carducci, M. Smith, R. Damião, J. Brown, L. Karsh, P. Milecki, N. Shore, M. Rader, H. Wang, Q. Jiang, S. Tadros, R. Dansey, C. Goessl, Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377, 813–822 (2011)PubMedCrossRef
68.
D.H. Henry, L. Costa, F. Goldwasser, V. Hirsh, V. Hungria, J. Prausova, G.V. Scagliotti, H. Sleeboom, A. Spencer, S. Vadhan-Raj, R. von Moos, W. Willenbacher, P.J. Woll, J. Wang, Q. Jiang, S. Jun, R. Dansey, H. Yeh, Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J. Clin. Oncol. 29, 1125–1132 (2011)PubMedCrossRef
69.
A.K. Gough, J. Lilley, S. Eyre, R.L. Holder, P. Emery, Generalized bone loss in patients with rheumatoid arthritis. Lancet 344, 23–27 (1994)PubMedCrossRef
70.
K. Nemeth, M. Schoppet, N. Al-Fakhri, S. Helas, R. Jessberger, L.C. Hofbauer, C. Goettsch, The role of osteoclast-associated receptor in osteoimmunology. J. Immunol. 186, 13–18 (2011)PubMedCrossRef
71.
E. Romas, N.A. Sims, D.K. Hards, M. Lindsay, J.W. Quinn, P.F. Ryan, C.R. Dunstan, T.J. Martin, M.T. Gillespie, Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. Am. J. Pathol. 161, 1419–1427 (2002)PubMedCrossRef
72.
S.B. Cohen, R.K. Dore, N.E. Lane, P.A. Ory, C.G. Peterfy, J.T. Sharp, D. van der Heijde, L. Zhou, W. Tsuji, R. Newmark, 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)PubMedCrossRef
73.
74.
D.H. Jones, T. Nakashima, O.H. Sanchez, I. Kozieradzki, S.V. Komarova, I. Sarosi, S. Morony, E. Rubin, R. Sarao, C.V. Hojilla, V. Komnenovic, Y.Y. Kong, M. Schreiber, S.J. Dixon, S.M. Sims, R. Khokha, T. Wada, J.M. Penninger, Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440, 692–696 (2006)PubMedCrossRef
75.
N. Frazl-Zelman, A. Valenta, P. Roschger, A. Nader, B.D. Gelb, P. Fratzl, K. Klaushofer, Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J. Clin. Endocrinol. Metab. 89, 1538–1547 (2004)CrossRef
76.
J.Y. Gauthier, N. Chauret, W. Cromlish, S. Desmarais, T. Duong le, J.P. Falgueyret, D.B. Kimmel, S. Lamontagne, S. Léger, T. LeRiche, C.S. Li, F. Massé, D.J. McKay, D.A. Nicoll-Griffith, R.M. Oballa, J.T. Palmer, M.D. Percival, D. Riendeau, J. Robichaud, G.A. Rodan, S.B. Rodan, C. Seto, M. Thérien, V.L. Truong, M.C. Venuti, G. Wesolowski, R.N. Young, R. Zamboni, W.C. Black, The discovery of odanacatib (MK0822), a selective inhibitor of cathepsin-K. Bioorg. Med. Chem. Lett. 18, 923–928 (2008)PubMedCrossRef
77.
S. Nagase, M. Ohyama, Y. Hashimoto, M. Small, T. Kuwayama, S. Deacon, Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple-dose, phase 1 study. J. Clin. Pharmacol. (2011) [Epub ahead of print]
78.
H.G. Bone, M.R. McClung, C. Roux, R.R. Recker, J.A. Eisman, N. Verbruggen, C.M. Hustad, C. DaSilva, A.C. Santora, B.A. Ince, Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J. Bone Miner. Res. 25, 937–947 (2010)PubMed
79.
S.E. Papapoulos, Targeting sclerostin as potential treatment of osteoporosis. Ann. Rheum. Dis. 70(Suppl 1), 19–22 (2011)CrossRef
80.
X. Li, M.S. Ominsky, K.S. Warmington, S. Morony, J. Gong, J. Cao, Y. Gao, V. Shalhoub, B. Tipton, R. Haldankar, Q. Chen, A. Winters, T. Boone, Z. Geng, Q.T. Niu, H.Z. Ke, P.J. Kostenuik, W.S. Simonet, D.L. Lacey, C. Paszty, 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)PubMedCrossRef
81.
M.S. Ominsky, F. Vlasseros, J. Jolette, S.Y. Smith, B. Stouch, G. Doellgast, J. Gong, Y. Gao, J. Cao, K. Graham, B. Tipton, J. Cai, R. Deshpande, L. Zhou, M.D. Hale, D.J. Lightwood, A.J. Henry, A.G. Popplewell, A.R. Moore, M.K. Robinson, D.L. Lacey, W.S. Simonet, C. Paszty, Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density and bone strength. J. Bone Miner. Res. 25, 948–959 (2010)PubMedCrossRef
82.
D. Padhi, G. Jang, B. Stouch, L. Fang, E. Posvar, Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J. Bone Miner. Res. 26, 19–26 (2011)PubMedCrossRef
83.
R.H. Giles, J.K. van Es, H. Clevers, Caught up in a Wnt storm: Wnt signalling in cancer. Biochem. Biophys. Acta 1653, 1–24 (2003)PubMed
84.
M. Kansara, M. Tsang, L. Kodjabachian, N.A. Sims, M.K. Trivett, M. Ehrich, A. Dobrovic, J. Slavin, P.F. Choong, P.J. Simmons, I.B. Dawid, D.M. Thomas, Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice. J. Clin. Invest. 119, 837–851 (2009)PubMedCrossRef
85.
A.A. Khan, G.K.B. Sandor, E. Dore, A.D. Morrison, M. Alsahli, F. Amin, E. Peters, D.A. Hanley, S.R. Chaudry, B. Lentle, D.W. Dempster, F.H. Glorieux, A.J. Neville, R.M. Talwar, C.M. Clokie, M.A. Mardini, T. Paul, S. Khosla, R.G. Josse, S. Sutherland, D.K. Lam, R.P. Carmichael, N. Blanas, D. Kendler, S. Petak, L.G. Ste-Marie, J. Brown, A.W. Evans, L. Rios, J.E. Compston, Bisphosphonate associated osteonecrosis of the jaw. J. Reumathol. 36, 478–490 (2009)
86.
J.C. Lo, F.S. O’Ryan, N.P. Gordon, J. Yang, R.L. Hui, D. Martin, M. Hutchinson, P.V. Lathon, G. Sanchez, P. Silver, M. Chandra, C.A. McCloskey, J.A. Staffa, M. Willy, J.V. Selby, A.S. Go, Predicting risk of osteonecrosis of the jaw with oral bisphosphonate exposure (PROBE) investigators. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J. Oral Maxillofac. Surg. 68, 243–253 (2010)PubMedCrossRef
87.
S.L. Ruggiero, T.B. Dodson, L.A. Assael, R. Landesberg, R.E. Marx, B. Mehrotra, American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonates-related osteonecrosis of the jaws: 2009 update. J. Oral Maxillofac. Surg. 67(Suppl 5), 2–12 (2009)PubMed
88.
J.E. Compston, Bisphosphonates and atypical femoral fractures: a time for reflection. Maturitas 65, 3–4 (2010)PubMedCrossRef
89.
E.M. Lewiecki, Safety of long-term bisphosphonate therapy for the management of osteoporosis. Drugs 71, 791–814 (2011)PubMedCrossRef
90.
M. Pazianas, J. Compston, C.L. Huang, Atrial fibrillation and bisphosphonate therapy. J. Bone Miner. Res. 25, 2–10 (2010)PubMedCrossRef
91.
E. Barrett-Connor, A.S. Swern, C.M. Hustad, H.G. Bone, U.A. Liberman, S. Papapoulos, H. Wang, A. de Papp, A.C. Santora, Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials. Osteoporos. Int. (2011) [Epub ahead of print]
92.
W. Wang, X. Zhang, J. Zheng, J. Yang, High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signalregulated kinase pathway. Mol. Cell. Biochem. 338, 115–122 (2010)PubMedCrossRef
93.
R.A. Kayal, D. Tsatsas, M.A. Bauer, B. Allen, M.O. Al-Sebaei, S. Kakar, C.W. Leone, E.F. Morgan, L.C. Gerstenfeld, T.A. Einhorn, D.T. Graves, Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity. J. Bone Miner. Res. 22, 560–568 (2007)PubMedCrossRef
94.
Y. Hamada, S. Kitazawa, R. Kitazawa, K. Kono, S. Goto, H. Komaba, H. Fujii, Y. Yamamoto, H. Yamamoto, M. Usami, M. Fukagawa, The effects of the receptor for advanced glycation end products (RAGE) on bone metabolism under physiological and diabetic conditions. Endocrine 38, 369–376 (2010)PubMedCrossRef
95.
M. Alikhani, Z. Alikhani, C. Boyd, C.M. MacLellan, M. Raptis, R. Liu, N. Pischon, P.C. Trackman, L. Gerstenfeld, D.T. Graves, Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 40, 345 (2007)PubMedCrossRef
96.
A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev. 29, 535–559 (2008)PubMedCrossRef
97.
A. Räkel, O. Sheehy, E. Rahme, J. LeLorier, Osteoporosis among patients with type 1 and type 2 diabetes. Diabetes Metab. 34, 193–205 (2008)PubMedCrossRef
98.
P. Vestergaard, L. Rejnmark, L. Mosekilde, Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48, 1292–1299 (2005)PubMedCrossRef
99.
P. Vestergaard, Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos. Int. 18, 427–444 (2007)PubMedCrossRef
100.
S. Bonadonna, G. Mazziotti, M. Nuzzo, A. Bianchi, A. Fusco, L. De Marinis, A. Giustina, Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J. Bone Miner. Res. 20, 1837–1844 (2005)PubMedCrossRef
101.
G. Mazziotti, A. Angeli, J.P. Bilezikian, E. Canalis, A. Giustina, Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol. Metab. 17, 144–149 (2006)PubMedCrossRef
102.
G. Mazziotti, A. Bianchi, S. Bonadonna, M. Nuzzo, V. Cimino, A. Fusco, L. De Marinis, A. Giustina, Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J. Bone Miner. Res. 21, 520–528 (2006)PubMedCrossRef
103.
G. Mazziotti, A. Bianchi, S. Bonadonna, V. Cimino, I. Patelli, A. Fusco, A. Pontecorvi, L. De Marinis, A. Giustina, Prevalence of vertebral fractures in men with acromegaly. J. Clin. Endocrinol. Metab. 93, 4649–4655 (2008)PubMedCrossRef
104.
G. Mazziotti, M. Gola, A. Bianchi, T. Porcelli, A. Giampietro, V. Cimino, M. Doga, C. Gazzaruso, L. De Marinis, A. Giustina, Influence of diabetes mellitus on vertebral fractures in men with acromegaly. Endocrine 40, 102–108 (2011)PubMedCrossRef
105.
G. Mazziotti, T. Mancini, M. Mormando, E. De Menis, A. Bianchi, M. Doga, T. Porcelli, P.P. Vescovi, L. De Marinis, A. Giustina, High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas. Pituitary 14, 299–306 (2011)PubMedCrossRef
106.
G. Mazziotti, T. Porcelli, M. Mormando, E. De Menis, A. Bianchi, C. Mejia, T. Mancini, L. De Marinis, A. Giustina, Vertebral fractures in males with prolactinoma. Endocrine 39, 288–293 (2011)PubMedCrossRef
107.
M. Viégas, C. Costa, A. Lopes, L. Griz, M.A. Medeiro, F. Bandeira, Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications. J. Diabetes Complications 25, 216–221 (2011)PubMedCrossRef
108.
P. Vestergaard, Risk of newly diagnosed type 2 diabetes is reduced in users of alendronate. Calcif. Tissue. Intern. (2011) [Epub ahead of print]
109.
M.S. Molinuevo, L. Schurman, A.D. McCarthy, A.M. Cortizo, M.J. Tolosa, M.V. Gangoiti, V. Arnol, C. Sedlinsky, Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J. Bone Miner. Res. 25, 211–221 (2010)PubMedCrossRef
110.
P. Ma, B. Gu, J. Ma, X. Wu, J. Cao, H. Liu, Glimepiride induces proliferation and differentiation of rat osteoblasts via the PI3-kinase/Akt pathway. Metabolism 59, 359–366 (2010)PubMedCrossRef
111.
V. Gopalakrishnan, R.C. Vignesh, J. Arunakaran, M.M. Aruldhas, N.E. Srinivasan, Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages. Biochem. Cell Biol. 84, 93–101 (2006)PubMedCrossRef
112.
B. Nuche-Berenguer, S. Portal-Núñez, P. Moreno, N. González, A. Acitores, A. López-Herradón, P. Esbrit, I. Valverde, M.L. Villanueva-Peñacarrillo, Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J. Cell. Physiol. 225, 585–592 (2010)PubMedCrossRef
113.
A. Grey, Skeletal consequences of thiazolidinedione therapy. Osteoporos. Int. 19, 129–137 (2008)PubMedCrossRef
114.
Y.K. Loke, S. Singh, C.D. Furberg, Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Can. Med. Assoc. J. 180, 32–39 (2009)CrossRef
115.
T. Mancini, G. Mazziotti, M. Doga, R. Carpinteri, N. Simetovic, P.P. Vescovi, A. Giustina, Vertebral fractures in males with type 2 diabetes treated with rosiglitazone. Bone 45, 784–788 (2009)PubMedCrossRef
116.
I.J. Douglas, S.J. Evans, S. Pocock, L. Smeeth, The risk of fractures associated with thiazolidinediones: a self-controlled case-series study. PLoS Med. 6, e1000154 (2009)PubMedCrossRef
117.
C.R. Dormuth, G. Carney, B. Carleton, K. Bassett, J.M. Wright, Thiazolidinediones and fractures in men and women. Arch. Intern. Med. 169, 1395–1402 (2009)PubMedCrossRef
118.
I. Kanazawa, T. Yamaguchi, M. Yamamoto, M. Yamauchi, S. Yano, T. Sugimoto, Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus. Eur. J. Endocrinol. 160, 265–273 (2009)PubMedCrossRef
Metadaten
Titel
New understanding and treatments for osteoporosis
verfasst von
G. Mazziotti
J. Bilezikian
E. Canalis
D. Cocchi
A. Giustina
Publikationsdatum
01.02.2012
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2012
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-011-9570-2

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