87
Views
21
CrossRef citations to date
0
Altmetric
Review

Clodronate: mechanisms of action on bone remodelling and clinical use in osteometabolic disorders

&
Pages 1643-1656 | Published online: 25 Feb 2005

REFERENCES

  • FLEISCH H: Bisphosphonates: history and experimental basis. Bone (1987) 8:523–528.
  • MENSCHUTKIN N: Veber die Einwirkung des Chloracetyls auf phosphorige Saure. Am. Chem. Pharm. (1865) 133:317–320.
  • VON BAYER H, HOFMANN KA: Acetodiphosphorige Saure. Vitt: Dtsch Chem. Ges. (1897) 30:1973–1978.
  • FLEISCH H, RUSSELL RGG, BISAZ S, CASEY PA, MUHLBAUER RC: The influence of pyrophosphate analogues (diphosphonates) on the precipitation and dissolution of calcium phosphate M vitro and in vivo. Ca/al Timm Res. (1968) 2:S10-S10A.
  • GLOWACKI Y: Studies on the regulation of bone synthesis and bone resorption. Frog. Clin. Biol. Res. (1982) 101:83–91.
  • SCHENK R, EGGLI P, FLEISCH H, ROSINI S: Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. Ca/dl Tissue Int. (1986) 38:342–349.
  • MUHLBAUER RC, BAUSSF, SCHENK R et al: BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J. Bone Muter. Res. (1991) 6:1003–1011.
  • MUHLBAUER RC: Mechanisms of action of bisphosphonates: information from animal models. In: Bisphosphonate on Bones. Bijvoet OLM, Fleisch HA, Canfield RE, Russell RGG (Eds.). Elsevier, Amsterdam (1995):177–197.
  • GREEN JR, MOLLER K, JAEGGI KA: Preclinical pharmacology of CGP 42446, a new, potent, heterocyclic bisphosphonate compound. I Bone Muter. Res. (1994) 9:745–751.
  • RICO H, AMO C, REVILLA M et al: Etidronate versus clodronate in the prevention of postovariectomy bone loss. An experimental study in rats. Clin. Exp. Rheumatol (1994) 12:301–304.
  • LEPOLA V, JALOVAARA P, VAANANEN K: The influence of clodronate on the torsional strength of the growing rat tibia in immobilization osteoporosis. Bone (1994) 15:367–371.
  • DOPPELT SH, NEER RM, POTTS JT Jr:Human parathyroid hormone 1-34-mediated hypercalcemia in a rat model, and its inhibition by dichloromethane diphosphonate. Cakil Tissue Int. (1981) 33:649–654.
  • JAEGER P, JONES W, BARON R, HAYSLETT JP: Modulation of hypercalcemia by dichloromethane diphosphonate and by calcitonin in a model of chronic primary hyperparathyroidism in rats. Epithelial calcium and phosphate transport: molecular and cellular aspects. Frog Clin Biol. Res. (1984) 168:375–380.
  • LICHT JH, MCVICKER M: Parathyroid-hormone-induced metabolic alkalosis in dogs. Min. Electrol. Metab. (1982) 8:78–91.
  • TROEHLER U, BONJOUR J-P, FLEISCH H: Interference of dichloromethane diphosphonate with parathyroid hormone effects at the bone but not at the kidney level. Min. Electrol Met. (1982) 7:122–126.
  • HOCK JM, HUMMERT JR, BOYCE R, FONSECA J, RAISZ LG: Resorption is not essential for the stimulation of bone growth by hPTH-(1-34) in rats in vivo. J. Bone Muter. Res. (1989) 4:449–458.
  • SIETSEMA WK, EBETINO FH, SALVAGNO AM, BE VAN JA: Antiresorptive dose-response relationships across three generations of bisphosphonates. Drugs Under Experim. Clin. Res. (1989) 15:389–396.
  • WEISBRODE S, CAPEN CC, PENDLEY II CB: Interaction of dichloromethylene diphosphonate and vitamin D on bone of thyroparathyroidectomized rats. Am. J. Pathol (1977) 89:137–152.
  • EVANS RA, WERGEDAL JE, BAYLINK DJ: Effect of dichloromethylene diphosphonate on bone metabolism in calcium and phosphorus-depleted rats. Min. Electra Metab. (1983) 9:119–124.
  • MUHLBAUER RC, RUSSELL RGG, WILLIAMS DA, FLEISCH H: The effects of diphosphonates, polyphosphates, and calcitonin on 'immobilisation osteoporosis' in rats. Ear: Clin. Invest. (1971) 1:336–344.
  • JEE WSS, BLACK HE, GOTCHERJE: Effect of dichloromethane diphosphonate on cortisol-induced bone loss in young adult rabbits. Clin. Orthop. Related Res. (1981) 156:39–51.
  • YARRINGTON JT, CAPEN CC, BLACK HE, RE R, NAGODE LA: Effect of dichloromethane diphosphonate on calcium homeostatic mechanisms in pregnant cows. Am. J. Pathol (1977) 83:615–632.
  • BROMMAGE R, BAXTER DC: Inhibitionof bone mineral loss during lactation by C12MBP. Calcif Tissue Int. (1990) 47:169–172.
  • WINK CS, ONGE M, PARKER B: Theeffects of dichloromethylene biphosphonate on osteoporotic femora of adult castrate male rats. Acta Anatomica (1985) 124:117–121.
  • WINK CS: A scanning electron-microscopic study of femoral bone surfaces from castrate rats treated with dichloromethylene biphosphonate. Acta Anat. (1986) 126:57–62.
  • GOTCHER JE, JEE WSS: The progress of the periodontal syndrome in the rice rat. J. Periodontal Res. (1981) 16:441–455.
  • LEONARD EP, REESE MV, MANDEL EJ: Comparison of the effects of ethane-1-hydroxy-1,1-diphosphonate and dichloromethylene diphosphonate upon periodontal bone resorption in rice rats. Arch. Oral Biol. (1979) 24:707–708.
  • OLSON HM, HAGEN A: Inhibition of post-extraction alveolar ridge resorption in rats by dichloromethane diphosphonate. J. Periodontal Res. (1982) 17:669–674.
  • SCHMIDT L, ROWE DJ: The effects of diphosphonates on alveolar bone loss. Quintessence Int. (1987) 18:497–501.
  • KOIVUKANGAS A, TUUKKANEN J, LEHENKARI P et al: Microstructural properties of bone in rat vertebra after long-term clodronate treatment. J. Bone Muter. Metab. (2002) 20:223–227.
  • FLEISCH H: The bisphosphonate ibandronate, given daily as well as discontinuously, decreases bone resorption and increases calcium retention as assessed by 45Ca kinetics in the intact rat. Osteoporosis Int. (1996) 6:166–170.
  • GUY JA, SHEA M, PETER CP, MORRISSEY R, HAYES WC: Continuous alendronate treatment throughout growth, maturation and aging in rats results in increases in bone mass and mechanical properties. Cakif Tissue Int. (1993) 53:283–288.
  • TOOLAN BC, SHEA M, MYERS ER et al.: Effects of 4-amino-1-hydroxy-butylidine bisphosphonate on bone biomechanics in rats. J. Bone Muter. Res. (1992) 7:1399–1406.
  • BALENA R, TOOLAN BC, SHEA M et al.: The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates. I Gin. Invest. (1993) 92:2577–2586.
  • KaastAD TS, REIKERAS 0, MADSEN JE et al.: Effects of clodronate on cortical and trabecular bone in ovariectomized rats on low calcium diet. Cakif Tissue Int. (1997) 61:158–164.
  • REYNOLDS JJ, MINKIN C, MORGAN DB, SPYCHER D, FLEISCH H: The effect of two diphosphonates on the resorption of mouse calvaria in vitro. Cakil Tissue Res. (1972) 10:302–313.
  • FLEISCH H, RUSSELL RGG, FRANCIS MD: Diphosphonates inhibit hydroxyapatite dissolution IP vitro and bone resorption in tissue culture and in vivo. Science (1969) 165:1262–1264.
  • FLEISCH H, RUSSELL RGG, BISAZ S,MUHLBAUER RC, WILLIAMS DA: The inhibitory effect of phosphonates on the formation of calcium phosphate crystals IP vitro and on aortic and kidney calcification in vivo. Eur. Gin. Invest. (1970) 1:12–18.
  • SCHENK R, MERZ WA, MUHLBAUER R, RUSSELL RGG, FLEISCH H: Effect of ethane-l-hydroxy-1, diphosphonate (EHDP) and dichloromethylene diphosphonate (C12MDP) on the calcification and resorption of cartilagene and bone in the tibial epiphysis and metaphysis of rats. Cakif Tissue Res. (1973) 11:196–214.
  • TAUBE T, ELOMAA I, BLOMQVIST C, BENETON MNC, KANIS JA: Comparative effects of clodronate and calcitonin on bone metastatic breast cancer: a histomorphometric study. Eur: Cancer (1993) 29A(12):1677–1681.
  • PASPALIARIS V, LEAVER DD: Clodronate inhibits contraction and prevents the action of 1-type calcium channel antagonists on vascular smooth muscle.' Bone Miner. Res. (1991) 6:835–841.
  • HOLLANDER W, PRUSTY S, NAGRAJ S, KIRKPATRICK B, PADDOCK J: Comparative effects of cetaben (PHB) and dichloromethylene diphosphonate (C12MDP) on the development of atherosclerosis in the cynomolgus monkey. Atherosclerosis (1978) 31:307–325.
  • YLITALO R, OKSALA 0, YLA-HERTTUALA S, URTTI A, MONKKONEN: Antiatherosclerotic effects of clodronate in rabbits. Pharmacol. Toxicol. (1993) 72 (Suppl. 2):Abstract 55.
  • YLITALO R, SYVALA H, TOUHIMAA P, YLITALO P: Suppression of immunoreactive macrophages in atheromatous lesions of rabbits by clodronate. Pharmacol. Toxicol. (2002) 90:139–143.
  • DUNN CL, GALINET LA, WU H, NUGENT RA, SCHLACHTER ST: Demonstration of novel anti-arthritic and anti-inflammatory effects of diphosphonates.j Pharm. Expel: Ther: (1993) 266:1691–1698.
  • FLORA L: Comparative antiinflammatory and bone protective effects of two diphosphonates in adjuvant arthritis. Arthritis Rheum. (1979) 22:340–346.
  • HYVONEN PM, KOWOLIK MJ: Influence of dichloromethylene bisphosphonate on the IP vitro phagocytosis of hydroxyapatite particles by rat peritoneal exudate cells: an electron microscopic and chemiluminescence study. Ann. Rheum. Dis. (1992) 51:203–209.
  • KINNE R, HOPPE R, SCHMIDT C, BUCHNER E, NURNBERG H: Established adjuvant arthritis (AA) can be treated by systemic application of clodronate containing multilamellar liposomes. Clin. Rheumatol. (1993) 12:134.
  • VAN LENT PLEM, VAN DEN HOEK AEM, VAN DEN BERSSELAAR LAM, DIJKSTRA CD, VAN ROOIJEN N: Role of synovial macrophages in experimental arthritis. Res. Immunol. (1992) 143:229–234.
  • SERRETTI R, CORE P, MUTI S, SALAFFI F: Influence of dichloromethylene diphosphonate on reactive oxygen species production by human neutrophils. Rheumatology Int. (1993) 13:135–138.
  • SAHNI M, GUENTHER HL, FLEISCH H, COLLIN P, MARTIN TJ: Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. Gin. Invest. (1993) 91:2004–2011.
  • MANSFIELD K, TEIXEIRA CC, ADAMS CS SHAPIRO M: Phosphate ions mediate chondrocyte apoptosis trough a plasma membrane transporter mechanism. Bone (2001) 28:1–8.
  • AMIN D, CORNELL SA, GUSTAFSON SK, NEEDLE SJ, ULLRICH JVV: Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. Lipid Res. (1992) 33:1657–1663.
  • LUCKMAN SP, HUGHES DE, COXON FP, GRAHAM R, RUSSELL RGG, ROGERS MJ: Nitrogen containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. I Bone Miner. Res. (1998) 13:581–589.
  • FISHER JE, ROGERS MJ, KALASHI JM: Alendronate mechanism of action: geranyilgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption and kinase activation IP vitro. Proc. Nati Acad. Sci. USA (1999) 96:133–138.
  • BERGSTROM JD, BOSTEDOR RG, MASSARACHIA PJ, RERSZKA AA, RODAN GA: Alendronate is a specific monomalor inhibitor of farnesyl diphosphate synthase. Arch. Biochem. Biophys. (2000) 373:231–241.
  • FAST DK, FELIX R, DOWSE., NEUMAN WF, FLEISH H: The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture. Biochem. J. (1978) 172:97–107.
  • REITSMA PH, TEITELBAUM SL, BIJVOET OLM, KAHN AJ: Differential action of the bisphosphonates (3-amino-l-hydroxypropyline)-1, 1-bisphophinate (APD) and disodium dichloromethylidene bisphosphonate (C12 MDP) on rat macrophage-mediated bone resorption IP vitro. .1. Clin. Invest. (1982) 70:927–933.
  • BOONEKAMP PM, VAN DER WEE-PALS LJA, VAN WIJK-VAN LENNER MML, THESING CW, BIJUOET OLM: The modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Min. (1986) 1:27–39.
  • HUGHES DE, MACDONALD BR, KUSSEL RGG, GOWEN M: Inhibition of osteoclast-like cells formation by bisphosphonates in long-term cultures of human bone marrow. I Clin. Invest. (1989) 83:1930–1935.
  • CARANO A, TEITELBAUM SL, KONSEK JD, SCHLESINGER PH, BLAIR HC: Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro.' Gin. Invest. (1990) 85:456–461.
  • HUGHES DE, WRIGHT KR, UY HL et al.: Bisphosphonates promote apoptosis in murine osteoclasts IP vitro and in vivo. Bone Miner. Res. (1995) 10:1478–1487.
  • ROGERS MJ, BROWN RJ, HODKIN V, BLACKBURN GM, RUSSELL RGG, WATTS DJ: Bisphosphonates are incapsulates into adenine nucleotides by human aminacyl-tRNA sinthetase enzymes. Biochem. Biophys. Res. Comm. (1996) 224:853-869. 1654
  • ROGERS MJ, JI X, RUSSELL RGG et al.: Incorporation of bisphosphonates into adenine nucleotides by amoebae of the cellular slime mould Dictyostelium discoideum. Biochem. J. (1994) 303:303–311.
  • ROGERS MJ, RUSSELL RGG, BALCKBURN GM, WILLIOAMSON MP, WATS DY: Metabolism of halogenates bisphosphonates by the cellular slime mould Dictyostelium Discoideum. Biochem. Biophys. Res. Comm. (1992) 189:414–423.
  • SELANDER KS, MONKKONEN J, KARMUKORPI EK, HARKONENE P, HANNUNIEMI R, VAANANEN HK: Characteristics of clodronate induced apoptosis in osteoclasts and macrophages. Mol. Pharmacol. (1996) 50:1127–1138.
  • FRITH JC, MONKKONEN J, BLACKBURN GM, RUSSELL RGG, ROGERS MJ: Clodronate and liposome-encapsulated clodronate are metabolized to atoxic ATP analog, adenosine 5-U3, y-dicloromethylene) triphosphate, by mammalian cells in vitro. J. Bone Miner. Res. (1997) 12:1358–1367.
  • LEHENKARI PP, KELLINSALMI M, NAPANKAN GAS JP et al.: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol. Pharmacol. (2002) 62:1255–1262.
  • TWISS IM, RAMP-KOOPMANSCHAP W, DEN HARTIGH J, VERMEIJ P: The effects of nitrogen containing bisphosphonate on human epithelial (Caco-2) cells, an in vitro model for intestinal epithelium. Bone Miner. Res. (1999) 14:784–791.
  • TOMALEHTO S, MONKKONEN H, RONKKO S, AURIOLA S, ROGERS MJ, MONKKONENEN J: Metabolism of clodronate into a nucleotide analogue of ATP in Caco-2 cell monolayers. Bone (2000) 26:325.
  • PENNANEN N, LAPINJOKI S, URTTI A, MONKKONEN J: Effect of liposomal and free bisphosphonates on the IL-113, IL-6 and TNFa secretion from RAW 264 cells in vitro. Flamm. Res. (1995) 12:916–922.
  • MAKKONEN N, H1RVONEN MR, TERAVAINEN T, SAVOLAINEN K, MOKKONEN J: Different effects of three bisphosphonates on nitric oxide production by RAW 264 macrophage-like cells in vitro. Pharmacol. Exp. Ther. (1996) 277:1097–1102.
  • NAKAMURA M, ANDO T, ABE M, KUMAGAI K, ENDO Y: Contrast between effects of aminobisphosphonates on non-aminobisphosphonates on collagen-induced arthritis in mice. Br. Pharmacol. (1996) 119:205–212.
  • SCHMIDT A, RUTLEDGE SJ, ENDO N et al.: Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Proc. Nati Acad. Sci. USA (1996) 93:3068–3073.
  • SASAKI A, BOYCE BE STORY Bet al.:Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone nude mice. Cancer Res. (1995) 55:3551–3557.
  • VAN DER PLUIYN G, VLOEDGRAVEN H, VAN BEEK E, VAN DER WEE-PALS L, LOWIK C, PAPAPOULOS S: Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. Clin. Invest. (1996) 98:698–705.
  • FROMIGUE 0, BODY JJ: Bisphosphonates induce cell apoptosis in MCF-7 cells, an effect partly reversed by IGEs. Bone (2000) 26:29S.
  • SHINODA H, ADAMEK G, FELIX R et al.: Structure-activity relationship of various bisphosphonates. Cakii Tissue Int. (1983) 35:87–99.
  • YACATAN GJ, POYNOR WJ, TALBERT RL, FLOYD BE SLOUGH CL: Clodronate kinetics and bioavailability. Clin. Pharmacol. Ther. (1982) 31:402–410.
  • PENTIKAINEN PJ, ELOMAA I, NURMI A-K, KARKKAINEN S: Pharmacokinetics of clodronate in patients with metastatic breast cancer. Int.' Clin. Pharm. Ther. Toxicol . (1989) 27:222–228.
  • MANHIJARVI H, ELOMAA I, KALSSON M, LAUREN L: Pharmacokinetics of disodium clodronate after daily intravenous infusions during five consecutive days. hat. Clin. Pharm. Ther. Toxicol. (1989) 27:602–606.
  • BOUNAMEAUX HM, SCHIFFERLI J, MONTANIJ-P, JUNG A, CHATELANAT F: Renal failure is associated with intravenous diphosphonates. Lancet (1983) 1:471.
  • HOSKING DJ: Advances in the management of Paget's disease of bone. Drugs (1990) 40:829–840.
  • RENDINA D, POSTIGLIONE L, VUOTTO P et al.: Clodronate reduces serum levels of interleukin-6 soluble in Paget's disease of bone. Clin. Exp. Rheumatol. (2002) 20:359–364.
  • ADAMI S, GUARRERA G, SAVAGNO G, SPIAZZI G, MARINI G: Sequential treatment of Paget's disease with human calcitonin and dichloromethylene diphosphonate (C12MDP). Met. Bone. Dis. Rel. Res. (1984) 5:265–267.
  • YATES AJP, PERCIVAL RC, GRAY RES, ATKINS RIVI, URWIN GM: Intravenous clodronate in the treatment and retreatment of Paget's disease of bone. Lancet (1985) 1:1474–1477.
  • GRAY RES, YATES AJP, PRESTON CJ,SMITH R, RUSSELL RGG: Duration of effect of oral diphosphonate therapy in Paget's disease of bone. QIM (1987) 64:755–767.
  • CHAPUY MC, CHARHON SA, MEUNIER PY: Sustained biochemical effect of short treatment of Pagef s disease of bone with dichlorometilene diphosphonate. Met. Bone Dis. Rel. Res. (1983) 4:325–328.
  • KANIS JA, MCCLOSKEY EV: The use ofclodronate in disorders of calcium and skeletal metabolism. In: Calcium metabolism. (Vol. 4). Progress in basic and clinical pharmacology. Kanis JA (Ed.), Karger, Basel, Switzerland(1990):89–136.
  • RIZZOLI R, FLEISCH H: The Walker 256/B Carcinosarcoma in thyroparathyroidectomized rats: a model to evaluate inhibitors of bone resorption. Cakii Tissue mt. (1987) 41:202–207.
  • HARJUNG H, FRITZE D: Results of treating tumor-induced hypercalcemia with clodronate alone. German Deutsche Medizinische Wochenschrift (1990) 115:48–52.
  • ZIEGLER R, SCHARLA SH: Treatment of human hypercalcemia with clodronate. Cancer Res. (1989) 116:46–53.
  • O'ROURKE NP, MCCLOSKEY EV, VASIKARAN S, EYRES K, FERN D: Effective treatment of malignant hypercalcemia with a single intravenous infusion of clodronate. Br. J. Cancer (1993) 37:560–563.
  • RALSTON SH, GARDNER MD, JENKINS AS, MCKILLOP JH, BOYLE IT: Malignancy-associated hypercalcemia: relationship between mechanisms of hypercalcemia and response to antihypercalcemic therapy. Bone MM. (1987) 2:227–242.
  • BAKOWSKI MT, SPITTLE MF: Double-shind placebo-controlled trial of bonefos (clodronate) in malignant hypercalcemia. Eur. Cancer(1991) 27:9289.
  • CHAPUY MC, MEUNIER PY, ALEXANDRE CM, VIGNON EP: Effects of disodium dichloromethylene diphosphonate on hypercalcemia traduced by bone metastases. Clin. Invest. (1980) 65:1243–1247.
  • DELMAS P, CHAPUY MC, VIGNON E, BRIANCON D, CHARHON S: Dichloromethylene diphosphonate (C12MDP) treatment of hypercalcemia produced from bone metastases. Nouvelle Presse Med. (1982) 11:1471–1474.
  • PATERSON AHG, POWLES TJ, KANIS YA, MCCLOSKEY E, HANSON Y, ASHLEY S: Double-controlled trial of oral clodronate in patienbts with bone metastases from breast cancer. J. Clin. Oncol (1993) 11:59–65.
  • DIEL TY, SOLOMAYER EF, GOLLAN C, WALLWIENER D, BASTERT G: Adjuvant clodronate treatment in patients with primary breast cancer reduces the incidence of subsequent metastases. Bone (1998) 22:575.
  • POWLES T, PATERSON S, ASHLEY S et al.: A placebo controlled trial of clodronate for prevention of metastases in patient with primary operable breast cancer. Bone (2000) 26:42S.
  • SALO T, KONTTINEN YT, LINDQVIST C, TERONEN 0. Inhibition of MMP-2 activation by clodronate in osteosarcoma MG 63 and U-205 cells. Bone (1998) 22:48S.
  • FILIPPONI P, PEDETTI M, FEDELI L et al.: Cyclical clodronate is effective in preventing postmenopausal bone loss: a comparative study with transcutaneous hormone replacement therapy. J. Bone Miner. Res. (1995) 10:697–703.
  • PLOSKER GL, GOA KL: Clodronate. A review of its pharmaceutical properties and therapeutic efficacy in resorptive bone disease. Drugs (1994) 47:945–985.
  • KANIS JA, MCCLOSKEY EV, BENETON MNC: Clodronate and osteoporosis. Maturitas (1996) 23:S81–S86.
  • MIRAIRE P, BERARD E, MEUNIER PJ, EDOUARD C, GOEDERT G, PILONCHERY G: Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. I Clin. Invest. (1981) 68:1086–1092.
  • ELOMAA I, BLOMQVIST C, PORKKA L, HOLMSTROM T: Experience of clodronate in treatment of multifocal eosinophilic granuloma of bone. J. Intern. Med. (1989) 225:59–61.
  • CUNDY T, BENETON MNC, DARBY AJ, MARSHALL WJ, KANIS JA: Osteopenia in systemic mastocytosis: natural history and responses to treatment with inhibitors of bone resorption. Bone (1987) 8:149–155.
  • KANIS JA: Pathophysiology and treatment of Paget's disease of bone. Martin Dunitz, London, UK (1991).
  • MCCLOSKEY EV, YATES AJP, BENETON MNC, GALLOWAY J, HARRIS S, KANIS JA: Comparative effects of intravenous diphosphonates on calcium and skeletal metabolism in man. Bone (1987) 8:S35–S41.
  • CHESNUT CH: Synthetic salmon calcitonin, diphosphonates and anabolic steroids in the treatment of postmenopausal osteoporosis. In: Osteoporosis. Proceedings of the Copenhagen International Symposium on Osteoporosis. Glostrup, Copenhagen: Aalborg Stiftsborgtrykkeri. Christiansen C, Arnaud CD, Nordin BEC, Parfitt AM, Peck WA, Riggs BL (Eds.). (1984):549–555.
  • GIANNINI S, D'ANGELO A, MALVASI L et al.: Effects of one-year cyclical treatment with clodronate on postmenopausal bone loss. Bone (1993) 14:137–141.
  • ROSSINI M, BRAGA V, GATTI D, ZAMBERLAN N, BIANCHINI D, ADAMI S: Intramuscular intermittent clodronate in the treatment of postmenopausal osteoporosis. Bone (1999) 16:606.
  • GIANNINI S, D'ANGELO A, SARTORI L, PASSER' G, DALLE CARBONARE L, CREPALDI G: Continuous and cyclical clodronate therapies and bone density in postmenopausal bone loss. Obstet. Cynecol (1996) 88:431–436.
  • FILIPPONI P, CRISTALLINT S, RIZZELLO E et al.: Cyclical intravenous alendronate in postmenopausal osteoporosis: results of a long-term cyclical trial. Bone (1996) 18:179–184.
  • HEIKKINEN JE, SELANDER KS, LAITINEN K, ARNALA I, VAANANEN HK: Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss. Bone Muter. Res. (1997) 12:103–110.
  • ROSSINI M, BRAGA V, GATTI D, GERARDI D, ZAMBERLAN N, ADAMI S: Intramuscolar clodronate therapy in postmenopausal osteoporosis. Bone (1999) 24:125–129.
  • FILIPPONI P, CRISTALLINI S, POLICANI G, SCHIFINI MF, CASCIARI C, GARINEI P: Intermittent versus continuous clodronate administration in postmenopausal women with low bone mass. Bone (2000) 26:269–274.
  • REID IR, BROWN JP, BURCKHARDT P et al.: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl. J. Med. (2002) 346:653–661.
  • BRANDI ML: I bisfosfonati per via iniettiva nelle malattie metaboliche dell'osso. Riv. It. Biol. Med. (1998) 18:1–6.
  • McCLOSKEY E, SELBY P, DE TAKATS D et al.: Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis. Bone (2001) 28:310–315.
  • MIAN M, BEGHE F, CAPRIO A: Tolerability and safety of clodronate therapy in bone diseases. Int. J. Clin. Pharmacol Res. (1991) 11:107–114.
  • BORGSTROM GM, ELOMAA I, BLOMQVIST C, PORKKA L: Cytogenic investigations in patients on clodronate therapy for Paget's disease of bone. Bone (1987) 8:S85–S86.
  • AHLMARK M, VEPSALAINEN J, TAIPALE H, NIEMI R, JARVINEN T: Bisphosphonate prodrugs: synthesis and in vitro evaluation of novel clodronic acid dianhydrides as bioreversible prodrugs of clodronate. Med. Chem. (1999) 42:1473–1476.
  • RALSTON SH, MCGUIGAN FEA, REID DM: Methods of targeting bisphosphonate therapy in osteoporosis: use of genetic markers in combination with bone density measurements. Bone (1998) 22:45S–64S.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.