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Published in: Osteoporosis International 10/2010

01-10-2010 | Original Article

Alendronate reduces osteoclast precursors in osteoporosis

Authors: P. D’Amelio, A. Grimaldi, M. A. Cristofaro, M. Ravazzoli, P. A. Molinatti, G. P. Pescarmona, G. C. Isaia

Published in: Osteoporosis International | Issue 10/2010

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Abstract

Summary

This study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women. We suggest that it acts on mature bone resorbing osteoclasts after 3 months of treatment, whereas, after 1 year, it diminishes their formation by reducing their precursors and serum RANKL.

Introduction

Osteoclasts are the target cells of bisphosphonates, though the most drug-sensitive steps of their formation and activity have not been determined. The present study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women.

Methods

The study was conducted on 35 osteoporotic women; 15 were pretreated with alendronate 70 mg/week, whereas, 20 were treated with calcium 1 g/day and vitamin D 800 IU/day. After 3 months, 30 received alendonate 70/mg, vitamin D 2800 IU/week, and calcium 1 g/day for 12 months (combined therapy), whereas, the other five patients remained on calcium 1 g/day and vitamin D 800 IU/day. The following parameters were assessed before and after therapy: changes in bone resorption markers, circulating osteoclast precursors, formation of osteoclasts in peripheral blood mononuclear cell cultures, their viability, and variations in cytokines production.

Results

After 3 months of alendronate, there was no significant reduction in the number of osteoclast precursors, osteoclast formation and viability, and cytokine levels, whereas, there was a significant reduction of bone resorption markers. One year of the combined therapy, on the other hand, reduced osteoclast precursors, osteoclast formation, and serum RANKL, whereas, calcium plus vitamin D alone had no effect.

Conclusions

We suggest that alendronate mainly acts on mature bone resorbing osteoclasts in the short term, whereas, its long-term administration diminishes their formation by reducing their precursors and serum RANKL.
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Literature
1.
go back to reference Rogers MJ (2003) New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 9:2643–2658CrossRefPubMed Rogers MJ (2003) New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 9:2643–2658CrossRefPubMed
2.
go back to reference Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28:465–473CrossRefPubMed Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28:465–473CrossRefPubMed
3.
go back to reference Sudhoff H, Jung JY, Ebmeyer J, Faddis BT, Hildmann H, Chole RA (2003) Zoledronic acid inhibits osteoclastogenesis in vitro and in a mouse model of inflammatory osteolysis. Ann Otol Rhinol Laryngol 112:780–786PubMed Sudhoff H, Jung JY, Ebmeyer J, Faddis BT, Hildmann H, Chole RA (2003) Zoledronic acid inhibits osteoclastogenesis in vitro and in a mouse model of inflammatory osteolysis. Ann Otol Rhinol Laryngol 112:780–786PubMed
4.
go back to reference Rogers MJ, Chilton KM, Coxon FP, Lawry J, Smith MO, Suri S, Russell RG (1996) Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism. J Bone Miner Res 11:1482–1491CrossRefPubMed Rogers MJ, Chilton KM, Coxon FP, Lawry J, Smith MO, Suri S, Russell RG (1996) Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism. J Bone Miner Res 11:1482–1491CrossRefPubMed
5.
go back to reference Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487CrossRefPubMed Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487CrossRefPubMed
6.
go back to reference Cecchini MG, Felix R, Fleisch H, Cooper PH (1987) Effect of bisphosphonates on proliferation and viability of mouse bone marrow-derived macrophages. J Bone Miner Res 2:135–142CrossRefPubMed Cecchini MG, Felix R, Fleisch H, Cooper PH (1987) Effect of bisphosphonates on proliferation and viability of mouse bone marrow-derived macrophages. J Bone Miner Res 2:135–142CrossRefPubMed
7.
go back to reference Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OL (1986) Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1:27–39PubMed Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OL (1986) Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1:27–39PubMed
9.
go back to reference Colucci S, Minielli V, Zambonin G, Cirulli N, Mori G, Serra M, Patella V, Zambonin Zallone A, Grano M (1998) Alendronate reduces adhesion of human osteoclast-like cells to bone and bone protein-coated surfaces. Calcif Tissue Int 63:230–235CrossRefPubMed Colucci S, Minielli V, Zambonin G, Cirulli N, Mori G, Serra M, Patella V, Zambonin Zallone A, Grano M (1998) Alendronate reduces adhesion of human osteoclast-like cells to bone and bone protein-coated surfaces. Calcif Tissue Int 63:230–235CrossRefPubMed
10.
go back to reference Carano A, Teitelbaum SL, Konsek JD, Schlesinger PH, Blair HC (1990) Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. J Clin Invest 85:456–461CrossRefPubMed Carano A, Teitelbaum SL, Konsek JD, Schlesinger PH, Blair HC (1990) Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. J Clin Invest 85:456–461CrossRefPubMed
11.
go back to reference Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88:2095–2105CrossRefPubMed Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88:2095–2105CrossRefPubMed
12.
go back to reference D'Amelio P, Grimaldi A, Di Bella S, Tamone C, Brianza SZ, Ravazzoli MG, Bernabei P, Cristofaro MA, Pescarmona GP, Isaia G (2008) Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women. J Bone Miner Res 23:373–379CrossRefPubMed D'Amelio P, Grimaldi A, Di Bella S, Tamone C, Brianza SZ, Ravazzoli MG, Bernabei P, Cristofaro MA, Pescarmona GP, Isaia G (2008) Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women. J Bone Miner Res 23:373–379CrossRefPubMed
13.
go back to reference Dobnig H, Hofbauer LC, Viereck V, Obermayer-Pietsch B, Fahrleitner-Pammer A (2006) Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Osteoporos Int 17:693–703CrossRefPubMed Dobnig H, Hofbauer LC, Viereck V, Obermayer-Pietsch B, Fahrleitner-Pammer A (2006) Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Osteoporos Int 17:693–703CrossRefPubMed
14.
go back to reference Sauty A, Pecherstorfer M, Zimmer-Roth I, Fioroni P, Juillerat L, Markert M, Ludwig H, Leuenberger P, Burckhardt P, Thiebaud D (1996) Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy. Bone 18:133–139CrossRefPubMed Sauty A, Pecherstorfer M, Zimmer-Roth I, Fioroni P, Juillerat L, Markert M, Ludwig H, Leuenberger P, Burckhardt P, Thiebaud D (1996) Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy. Bone 18:133–139CrossRefPubMed
15.
go back to reference Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK (2005) The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 139:101–111CrossRefPubMed Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK (2005) The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 139:101–111CrossRefPubMed
16.
go back to reference Thompson K, Rogers MJ (2004) Statins prevent bisphosphonate-induced gamma, delta-T-cell proliferation and activation in vitro. J Bone Miner Res 19:278–288CrossRefPubMed Thompson K, Rogers MJ (2004) Statins prevent bisphosphonate-induced gamma, delta-T-cell proliferation and activation in vitro. J Bone Miner Res 19:278–288CrossRefPubMed
17.
go back to reference Mossetti G, Rendina D, De Filippo G, Viceconti R, Di Domenico G, Cioffi M, Postiglione L, Nunziata V (2005) Interleukin-6 and osteoprotegerin systems in Paget's disease of bone: relationship to risedronate treatment. Bone 36:549–554CrossRefPubMed Mossetti G, Rendina D, De Filippo G, Viceconti R, Di Domenico G, Cioffi M, Postiglione L, Nunziata V (2005) Interleukin-6 and osteoprotegerin systems in Paget's disease of bone: relationship to risedronate treatment. Bone 36:549–554CrossRefPubMed
18.
go back to reference Papadaki HA, Tsatsanis C, Christoforidou A, Malliaraki N, Psyllaki M, Pontikoglou C, Miliaki M, Margioris AN, Eliopoulos GD (2004) Alendronate reduces serum TNFalpha and IL-1beta, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis. J Bone Miner Metab 22:577–587CrossRefPubMed Papadaki HA, Tsatsanis C, Christoforidou A, Malliaraki N, Psyllaki M, Pontikoglou C, Miliaki M, Margioris AN, Eliopoulos GD (2004) Alendronate reduces serum TNFalpha and IL-1beta, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis. J Bone Miner Metab 22:577–587CrossRefPubMed
19.
go back to reference Santini D, Fratto ME, Vincenzi B, La Cesa A, Dianzani C, Tonini G (2004) Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. BioDrugs 18:269–278CrossRefPubMed Santini D, Fratto ME, Vincenzi B, La Cesa A, Dianzani C, Tonini G (2004) Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. BioDrugs 18:269–278CrossRefPubMed
20.
go back to reference Gur A, Denli A, Cevik R, Nas K, Karakoc M, Sarac AJ (2003) The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study. Yonsei Med J 44:99–109PubMed Gur A, Denli A, Cevik R, Nas K, Karakoc M, Sarac AJ (2003) The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study. Yonsei Med J 44:99–109PubMed
21.
go back to reference Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ (1993) Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004–2011CrossRefPubMed Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ (1993) Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004–2011CrossRefPubMed
22.
go back to reference Vitte C, Fleisch H, Guenther HL (1996) Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption. Endocrinology 137:2324–2333CrossRefPubMed Vitte C, Fleisch H, Guenther HL (1996) Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption. Endocrinology 137:2324–2333CrossRefPubMed
23.
go back to reference Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381CrossRefPubMed Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381CrossRefPubMed
24.
go back to reference D'Amelio P, Grimaldi A, Pescarmona GP, Tamone C, Roato I, Isaia G (2005) Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis. Faseb J 19:410–412PubMed D'Amelio P, Grimaldi A, Pescarmona GP, Tamone C, Roato I, Isaia G (2005) Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis. Faseb J 19:410–412PubMed
25.
go back to reference Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111:821–831PubMed Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111:821–831PubMed
26.
go back to reference Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, Haskard DO, McQueen FM, Reid IR, Cornish J (2008) Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum 58:1854–1865CrossRefPubMed Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, Haskard DO, McQueen FM, Reid IR, Cornish J (2008) Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum 58:1854–1865CrossRefPubMed
27.
go back to reference Ramnaraine M, Pan W, Clohisy DR (2006) Osteoclasts direct bystander killing of cancer cells in vitro. Bone 38:4–12CrossRefPubMed Ramnaraine M, Pan W, Clohisy DR (2006) Osteoclasts direct bystander killing of cancer cells in vitro. Bone 38:4–12CrossRefPubMed
28.
go back to reference Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106:167–170CrossRefPubMed Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106:167–170CrossRefPubMed
29.
go back to reference Shalhoub V, Elliott G, Chiu L, Manoukian R, Kelley M, Hawkins N, Davy E, Shimamoto G, Beck J, Kaufman SA, Van G, Scully S, Qi M, Grisanti M, Dunstan C, Boyle WJ, Lacey DL (2000) Characterization of osteoclast precursors in human blood. Br J Haematol 111:501–512CrossRefPubMed Shalhoub V, Elliott G, Chiu L, Manoukian R, Kelley M, Hawkins N, Davy E, Shimamoto G, Beck J, Kaufman SA, Van G, Scully S, Qi M, Grisanti M, Dunstan C, Boyle WJ, Lacey DL (2000) Characterization of osteoclast precursors in human blood. Br J Haematol 111:501–512CrossRefPubMed
30.
go back to reference Faust J, Lacey DL, Hunt P, Burgess TL, Scully S, Van G, Eli A, Qian Y, Shalhoub V (1999) Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors. J Cell Biochem 72:67–80CrossRefPubMed Faust J, Lacey DL, Hunt P, Burgess TL, Scully S, Van G, Eli A, Qian Y, Shalhoub V (1999) Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors. J Cell Biochem 72:67–80CrossRefPubMed
31.
go back to reference Matayoshi A, Brown C, DiPersio JF, Haug J, Abu-Amer Y, Liapis H, Kuestner R, Pacifici R (1996) Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells. Proc Natl Acad Sci USA 93:10785–10790CrossRefPubMed Matayoshi A, Brown C, DiPersio JF, Haug J, Abu-Amer Y, Liapis H, Kuestner R, Pacifici R (1996) Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells. Proc Natl Acad Sci USA 93:10785–10790CrossRefPubMed
32.
go back to reference Roato I, Grano M, Brunetti G, Colucci S, Mussa A, Bertetto O, Ferracini R (2005) Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. Faseb J 19:228–230PubMed Roato I, Grano M, Brunetti G, Colucci S, Mussa A, Bertetto O, Ferracini R (2005) Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. Faseb J 19:228–230PubMed
33.
go back to reference van Beek ER, Lowik CW, Papapoulos SE (1997) Effect of alendronate treatment on the osteoclastogenic potential of bone marrow cells in mice. Bone 20:335–340CrossRefPubMed van Beek ER, Lowik CW, Papapoulos SE (1997) Effect of alendronate treatment on the osteoclastogenic potential of bone marrow cells in mice. Bone 20:335–340CrossRefPubMed
34.
go back to reference Van Beek ER, Lowik CW, Papapoulos SE (2002) Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates on osteoclast precursors. Bone 30:64–70CrossRefPubMed Van Beek ER, Lowik CW, Papapoulos SE (2002) Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates on osteoclast precursors. Bone 30:64–70CrossRefPubMed
35.
go back to reference Coxon FP, Thompson K, Roelofs AJ, Ebetino FH, Rogers MJ (2008) Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone 42:848–860CrossRefPubMed Coxon FP, Thompson K, Roelofs AJ, Ebetino FH, Rogers MJ (2008) Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone 42:848–860CrossRefPubMed
36.
go back to reference D'Amelio P, Grimaldi A, Di Bella S, Brianza SZ, Cristofaro MA, Tamone C, Giribaldi G, Ulliers D, Pescarmona GP, Isaia G (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone 43:92–100CrossRefPubMed D'Amelio P, Grimaldi A, Di Bella S, Brianza SZ, Cristofaro MA, Tamone C, Giribaldi G, Ulliers D, Pescarmona GP, Isaia G (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone 43:92–100CrossRefPubMed
37.
go back to reference Brunetti G, Colucci S, Pignataro P, Coricciati M, Mori G, Cirulli N, Zallone A, Grassi FR, Grano M (2005) T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients. J Periodontol 76:1675–1680CrossRefPubMed Brunetti G, Colucci S, Pignataro P, Coricciati M, Mori G, Cirulli N, Zallone A, Grassi FR, Grano M (2005) T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients. J Periodontol 76:1675–1680CrossRefPubMed
38.
go back to reference Olivier BJ, Schoenmaker T, Mebius RE, Everts V, Mulder CJ, van Nieuwkerk KM, de Vries TJ, van der Merwe SW (2008) Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia. Hepatology 47:259–267CrossRefPubMed Olivier BJ, Schoenmaker T, Mebius RE, Everts V, Mulder CJ, van Nieuwkerk KM, de Vries TJ, van der Merwe SW (2008) Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia. Hepatology 47:259–267CrossRefPubMed
39.
go back to reference Tjoa ST, de Vries TJ, Schoenmaker T, Kelder A, Loos BG, Everts V (2008) Formation of osteoclast-like cells from peripheral blood of periodontitis patients occurs without supplementation of macrophage colony-stimulating factor. J Clin Periodontol 35:568–575CrossRefPubMed Tjoa ST, de Vries TJ, Schoenmaker T, Kelder A, Loos BG, Everts V (2008) Formation of osteoclast-like cells from peripheral blood of periodontitis patients occurs without supplementation of macrophage colony-stimulating factor. J Clin Periodontol 35:568–575CrossRefPubMed
40.
go back to reference Hofbauer LC, Kuhne CA, Viereck V (2004) The OPG/RANKL/RANK system in metabolic bone diseases. JMNI 4:268–275PubMed Hofbauer LC, Kuhne CA, Viereck V (2004) The OPG/RANKL/RANK system in metabolic bone diseases. JMNI 4:268–275PubMed
41.
go back to reference Roato I, Brunetti G, Gorassini E, Grano M, Colucci S, Bonello L, Buffoni L, Manfredi R, Ruffini E, Ottaviani D, Ciuffreda L, Mussa A, Ferracini R (2006) IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor. PLoS ONE 1:e124CrossRefPubMed Roato I, Brunetti G, Gorassini E, Grano M, Colucci S, Bonello L, Buffoni L, Manfredi R, Ruffini E, Ottaviani D, Ciuffreda L, Mussa A, Ferracini R (2006) IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor. PLoS ONE 1:e124CrossRefPubMed
42.
go back to reference De Vries TJ, Everts V (2009) Osteoclast formation from peripheral blood of patients with bone-lytic diseases De Vries TJ, Everts V (2009) Osteoclast formation from peripheral blood of patients with bone-lytic diseases
43.
go back to reference Deng X, Yu Z, Funayama H, Yamaguchi K, Sasano T, Sugawara S, Endo Y (2007) Histidine decarboxylase-stimulating and inflammatory effects of alendronate in mice: involvement of mevalonate pathway, TNFalpha, macrophages, and T-cells. Int Immunopharm 7:152–161CrossRef Deng X, Yu Z, Funayama H, Yamaguchi K, Sasano T, Sugawara S, Endo Y (2007) Histidine decarboxylase-stimulating and inflammatory effects of alendronate in mice: involvement of mevalonate pathway, TNFalpha, macrophages, and T-cells. Int Immunopharm 7:152–161CrossRef
44.
go back to reference Pietschmann P, Stohlawetz P, Brosch S, Steiner G, Smolen JS, Peterlik M (1998) The effect of alendronate on cytokine production, adhesion molecule expression, and transendothelial migration of human peripheral blood mononuclear cells. Calcif Tissue Int 63:325–330CrossRefPubMed Pietschmann P, Stohlawetz P, Brosch S, Steiner G, Smolen JS, Peterlik M (1998) The effect of alendronate on cytokine production, adhesion molecule expression, and transendothelial migration of human peripheral blood mononuclear cells. Calcif Tissue Int 63:325–330CrossRefPubMed
45.
go back to reference Toyras A, Ollikainen J, Taskinen M, Monkkonen J (2003) Inhibition of mevalonate pathway is involved in alendronate-induced cell growth inhibition, but not in cytokine secretion from macrophages in vitro. Eur J Pharm Sci 19:223–230CrossRefPubMed Toyras A, Ollikainen J, Taskinen M, Monkkonen J (2003) Inhibition of mevalonate pathway is involved in alendronate-induced cell growth inhibition, but not in cytokine secretion from macrophages in vitro. Eur J Pharm Sci 19:223–230CrossRefPubMed
46.
go back to reference Pan B, Farrugia AN, To LB, Findlay DM, Green J, Lynch K, Zannettino AC (2004) The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). J Bone Miner Res 19:147–154CrossRefPubMed Pan B, Farrugia AN, To LB, Findlay DM, Green J, Lynch K, Zannettino AC (2004) The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). J Bone Miner Res 19:147–154CrossRefPubMed
47.
go back to reference Russell RG, Watts NB, Ebetino FH, Rogers MJ (2008) Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733–759CrossRefPubMed Russell RG, Watts NB, Ebetino FH, Rogers MJ (2008) Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733–759CrossRefPubMed
48.
go back to reference Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257CrossRefPubMed Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257CrossRefPubMed
Metadata
Title
Alendronate reduces osteoclast precursors in osteoporosis
Authors
P. D’Amelio
A. Grimaldi
M. A. Cristofaro
M. Ravazzoli
P. A. Molinatti
G. P. Pescarmona
G. C. Isaia
Publication date
01-10-2010
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 10/2010
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-009-1129-1

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