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New Bisphosphonates in the Treatment of Bone Diseases

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Abstract

Bisphosphonates are pyrophosphate analogues, in which the oxygen in P-O-P has been replaced by a carbon, resulting in a P-C-P structure. They are characterised by a strong anti-osteoclastic activity and for this pharmacological property they are now considered the treatment of choice for Paget’s disease of the bone, malignant hypercalcaemia and bone metastases. Etidronate, clodronate and pamidronate have been registered in several countries for these indications. Etidronate and alendronate are also extensively used for the prevention and treatment of postmenopausal and senile osteoporosis. In this article, we review the most recent findings on the newest bisphosphonates, which will become available in the near future.

The aminobisphosphonate risedronate is undergoing a huge programme of clinical development for the treatment of osteoporosis. In a study of the prevention of early postmenopausal bone loss, oral risedronate 5mg fully prevented the bone loss observed in the placebo group. Similar effects have been observed with an intermittent dosage regimen of oral risedronate 30 mg/day for 2 out of 12 weeks, which corresponds to 5 mg/day in terms of cumulative dose. With lower doses [5mg on alternate fortnights (2 weeks)] the prevention of bone loss was half that observed with continuous 5 mg/day therapy, indicating that this might not yet be the maximum effective dose.

The use of intermittent intravenous bisphosphonates for osteoporosis therapy has been pioneered by studies with clodronate, pamidronate and alendronate. This treatment regimen has been chosen for an extensive clinical development programme for ibandronate. In a phase 2 study, this new bisphosphonate was administered as an intravenous bolus (0.25, 0.5, 1 or 2 mg) every 3 months for a year, with increases in spinal bone mass of 5.2%.

Tiludronate, alendronate and risedronate have been recently introduced for the treatment of Paget’s disease of bone. Daily doses of tiludronate 400mg, alendronate 40mg and risedronate 30mg for 3 to 6 months have been shown to be superior to etidronate 400 mg/day. The intravenous administration of ibandronate, zoledronate and alendronate (40mg, 10mg and 5mg, respectively) have achieved the normalisation of serum alkaline phosphatase in more than 70% of the patients and these treatments may provide an alternative for patients intolerant oral bisphosphonates.

Intravenous ibandronate has been also developed for the treatment of hypercalcaemia of malignancy. The effective doses ranged from 2 to 4mg. Zoledronate appears to be the most powerful bisphosphonate under investigation, and the effective doses used in cancer hypercalcaemia are as low as 1 to 2mg.

The new generation of bisphosphonates are likely to increase clinical options in terms of administration regimens, but their real advantage over those already available in terms of clinical efficacy remains uncertain.

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References

  1. Fleish H. Bisphosphonates: mechanism of action and clinical use. In: Mundy GR, Martin TJ, editors. Physiology and pharmacology of bone: handbook of experimental pharmacology. New York: Springer-Verlag, 1993: 377–418

    Chapter  Google Scholar 

  2. Fleish H. Bisphosphonates: mechanism of action and clinical use. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. San Diego: Academic Press, 1996: 1037–52

    Google Scholar 

  3. Geddes AD, D’Souza SM, Ebetino FH, et al. Bisphosphonates: structure activity relationship and therapeutic implications. J Bone Miner Res 1994; 8: 265–306

    CAS  Google Scholar 

  4. Luckman SP, Hughes DE, Coxon FP, et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including rats. J Bone Miner Res 1998; 13: 581–9

    Article  PubMed  CAS  Google Scholar 

  5. Frith JC, Monkkonen J, Blackburn GM, et al. Clodronate and liposome-encapsualted clodronate are metabolized to atoxis ATP analog, adenosine 5′-beta, gamma-dichloromethylene triphosphate, by mammalian cells in vitro. J Bone Miner Res 1997; 12: 1358–67

    Article  PubMed  CAS  Google Scholar 

  6. Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995; 10: 1478–87

    Article  PubMed  CAS  Google Scholar 

  7. Johansen A, Stone M, Rawlinson F. Bisphosphonates and the treatment of bone disease in the elderly. Drug Aging 1996; 8(2): 113–26

    Article  CAS  Google Scholar 

  8. Adami S, Zamberlan N. Adverse effects of bisphosphonates. Drug Saf 1996; 14(3): 158–70

    Article  PubMed  CAS  Google Scholar 

  9. Papapoulos SE. Pharmacodynamics of bisphosphonates in man: implication for treatment. In: Bijovet OLM, Fleish H, Canfield RE, et al., editors. Bisphosphonate on bones. Amsterdam: Elsevier, 1995: 231–63

    Google Scholar 

  10. Adami S, Zamberlan N, Mian M, et al. Duration of the effects of intravenous alendronate in postmenopausal women and in patients with primary hyperparathyroidism. Bone Miner 1994; 25: 75–82

    Article  PubMed  CAS  Google Scholar 

  11. Sato M, Grasser W, Naoto E, et al. Bisphosphonate action: alendronate localization in rat bone and effects on osteoclasts culture. J Clin Invest 1991; 88: 2095–105

    Article  PubMed  CAS  Google Scholar 

  12. Masarachia P, Weinreb M, Balena R, et al. Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and mouse bones. Bone 1996; 19: 281–90

    Article  PubMed  CAS  Google Scholar 

  13. Sahni M, Guenther HL, Fleisch H, et al. Bisphosphonates act on rat bone resorption trough the mediation of osteoblasts. J Clin Invest 1993; 91: 2004–11

    Article  PubMed  CAS  Google Scholar 

  14. Sato M, Grasser W. Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. J Bone Miner Res 1990; 5: 31–40

    Article  PubMed  CAS  Google Scholar 

  15. Boonekamp PM, van der Wee-Pals LJA, van Wijk-van Lennep MM, et al. Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1986; 1: 27–39

    PubMed  CAS  Google Scholar 

  16. Flora L, Hassing GS, Cloyd GG, et al. The long-term skeletal effects of EHDP in dogs. Metab Bone Dis Relat Res 1981; 4/5: 289–300

    Article  Google Scholar 

  17. Storm T, Steiniche T, Thamsborg G, et al. Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis. J Bone Miner Res 1993; 8(2): 199–208

    Article  PubMed  CAS  Google Scholar 

  18. Ott SM, Woodson GC, Huffer WE, et al. Bone histomorphometric changes after cyclic therapy with phosphate and etidronate disodium in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 1994; 78: 968–72

    Article  PubMed  CAS  Google Scholar 

  19. Miller PD, Watts NB, Licata AA, et al. Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment. Am J Med 1997; 103: 468–76

    Article  PubMed  CAS  Google Scholar 

  20. Adami S, Bhalla AK, Dorizzi R, et al. The acute-phase response after bisphosphonates administration. Calcif Tissue Int 1987; 41: 326–31

    Article  PubMed  CAS  Google Scholar 

  21. Schweitzer DH, Oostendorp-van der Ruit M, van de Pluijm G, et al. Interleukin-6 and the acute phase response during treatment of patients with Paget’s disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate. J Bone Miner Res 1995; 6: 956–62

    Google Scholar 

  22. De Groen PC, Lubbe DF, Hirsh LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 355(14): 1016–21

    Article  Google Scholar 

  23. Melton LJ, Chrischilles EA, Cooper C, et al. Perspective: how many women have osteoporosis. J Bone Miner Res 1992; 7: 1005–10

    Article  PubMed  Google Scholar 

  24. Chrischilles EA, Butler CD, Davis CS, et al. Amodel of lifetime osteoporosis impact. Arch Intern Med 1991; 151: 2026–32

    Article  PubMed  CAS  Google Scholar 

  25. Cummings S, Black D, Nevitt M, et al. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341: 72–5

    Article  PubMed  CAS  Google Scholar 

  26. Adami S, Kanis JA. Assessment of involutional bone loss: methodological and conceptual problems. J Bone Miner Res 1995; 10: 511–7

    Article  PubMed  CAS  Google Scholar 

  27. Herd RJM, Balena R, Black LM, et al. The prevention of early postmenopausal bone loss by cyclic etidronate therapy; a 2-year, double-blind, placebo-controlled study. Am J Med 1997; 103: 92–9

    Article  PubMed  CAS  Google Scholar 

  28. Meunier PJ, Confavreux E, Tupinon I, et al. Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up). J Clin Endocrinol Metab 1997; 82: 2784–91

    Article  PubMed  CAS  Google Scholar 

  29. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997; 337: 382–421

    Article  PubMed  CAS  Google Scholar 

  30. Watts NB, Harris ST, Genant HG, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990; 323: 73–9

    Article  PubMed  CAS  Google Scholar 

  31. Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990; 322(18): 1265–71

    Article  PubMed  CAS  Google Scholar 

  32. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures: Fracture Intervention Trial Research Group. Lancet 1996; 348: 1535–41

    Article  PubMed  CAS  Google Scholar 

  33. Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis: the Glucocorticoid-induced Osteoporosis Intervention Study Group. N Engl J Med 1998; 339(5): 292–9

    Article  PubMed  CAS  Google Scholar 

  34. Reginster JY, Lecart MP, Deroisy R, et al. Prevention of postmenopausal bone loss by tiludronate. Lancet 1989; II: 1469–71

    Article  Google Scholar 

  35. Mortensen L, Charles P, Bekker PJ, et al. Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow up. J Clin Endocrinol Metab 1998; 83(2): 396–402

    Article  PubMed  CAS  Google Scholar 

  36. McClung M, Clemmesen B, Daifotis A. Alendronate prevents postmenopausal bone loss in women without osteoporosis. Ann Intern Med 1998; 128(4): 253–61

    PubMed  CAS  Google Scholar 

  37. Rossini M, Gatti D, Zamberlan N, et al. Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Miner Res 1994; 11: 1833–7

    Google Scholar 

  38. Stock JL, Bell NH, Chesnut III CH, et al. Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women. Am J Med 1997; 103: 291–7

    Article  PubMed  CAS  Google Scholar 

  39. Delmas PD, Balena R, Confravreux E. Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer; a double-blind placebo controlled study. J Clin Oncol 1997; 15(3): 955–62

    PubMed  CAS  Google Scholar 

  40. Passeri M, Baroni MC, Pedrazzoni M, et al. Intermittent treatment with intravenous 4-amino-l-hydroxybutylidene-1,1-bisphosphonate (AHButBP) in the therapy of postmenopausal osteoporosis. Bone Miner 1991; 15: 237–48

    Article  PubMed  CAS  Google Scholar 

  41. Thiébaud D, Burckardt P, Melchior J, et al. Two years effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the menopause. Osteoporosis Int 1994; 4: 76–83

    Article  Google Scholar 

  42. Filipponi P, Pedretti 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

    Article  PubMed  CAS  Google Scholar 

  43. Thiébaud D, Burckhardt P, Kriegbaum H, et al. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med 1997; 103: 298–307

    Article  PubMed  Google Scholar 

  44. Ravn P, Clemmensen B, Riis BJ, et al. The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo controlled dose finding study. Bone 1996; 19(10): 527–33

    Article  PubMed  CAS  Google Scholar 

  45. Singer FR, Roodman GD. Paget’s disease of bone. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. San Diego (CA): Academic Press, 1996: 969–77

    Google Scholar 

  46. Patel S, Lyons AR, Hosking DJ. Drugs used in the treatment of metabolic bone disease: clinical pharmacology and therapeutic use. Drugs 1993; 46(4): 594–617

    Article  PubMed  CAS  Google Scholar 

  47. Dunn CJ, Fitton A, Sorkin EM. Etidronic acid: a review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drug Aging 1994; 5: 446–74

    Article  CAS  Google Scholar 

  48. Gibbs CJ, Aaron JE, Peacock M. Osteomalacia in Paget’s disease treated with short-term, high dose sodium etidronate. BMJ 1986; 292: 1227–9

    Article  PubMed  CAS  Google Scholar 

  49. Kanis JA, McCloskey EV. The use of clodronate in disorders of calcium and skeletal metabolism. In: Kanis JA, editors. Calcium metabolism: progress in basic and clinical pharmacology. Basel: Karger, 1990; 4: 89–136

    Google Scholar 

  50. Fitton A, McTavish D. Pamidronate: a review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs 1991; 41: 289–318

    Article  PubMed  CAS  Google Scholar 

  51. Papapoulos SE, Frölich M. Prediction of the outcome of treatment of Paget’s disease of bone with bisphosphonates from short term changes in the rate of bone resorption. J Clin Endocrinol Metab 1996; 81(11): 3993–7

    Article  PubMed  CAS  Google Scholar 

  52. Cundy T, Wattie D, King AR. High dose pamidronate in the management of resistant Paget’s disease. Calcif Tissue Int 1996; 58: 6–8

    Article  PubMed  CAS  Google Scholar 

  53. McClung MR, Tou CKP, Goldstein NH, et al. Tiludronate therapy for Paget’s disease of bone. Bone 1995; 17 Suppl.: 493S–6

    Article  PubMed  CAS  Google Scholar 

  54. Roux C, Gennari C, Farrerons J, et al. Comparative prospective, double blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget’s bone disease of bone. Arthritis Rheum 1995; 6: 851–8

    Article  Google Scholar 

  55. Devogelaer JP, Malghem J, Stasse P, et al. Biological and radiological responses to oral etidronate and tiludronate in Paget’s disease of bone. Bone 1997; 20(3): 259–61

    Article  PubMed  CAS  Google Scholar 

  56. Adami S, Mian M, Gatti D, et al. Effects of two oral doses of alendronate in the treatment of Paget’s disease of bone. Bone 1994; 15: 415–7

    Article  PubMed  CAS  Google Scholar 

  57. Siris E, Weinstein RS, Altaian R, et al. Comparative study of alendronate versus etidronate for the treatment of Paget’s bone disease of bone. J Clin Endocrinol Metab 1996; 81: 961–7

    Article  PubMed  CAS  Google Scholar 

  58. Reid IR, Nicholson GC, Weinstein RS, et al. Biochemical and radiological improvement in Paget’s disease of bone treated with alendronate: a randomized placebo controlled trial. Am J Med 1996; 101(4): 341–8

    Article  PubMed  CAS  Google Scholar 

  59. Khan SA, Vasikaran S, McCloskey EV, et al. Alendronate in the treatment of Paget’s disease of bone. Bone 1997; 20(3): 263–71

    Article  PubMed  CAS  Google Scholar 

  60. Singer FR, Clemens TL, Rachelle AE, et al. Risedronate, a highly effective oral agent in the treatment of patients with severe Paget’s disease. J Clin Endocrinol Metab 1998; 83(6): 1906–10

    Article  PubMed  CAS  Google Scholar 

  61. Hosking DJ, Eusebio RA, Chines AA. Paget’s disease of bone: reduction of disease activity with oral risedronate. Bone 1998; 22(1): 51–5

    Article  PubMed  CAS  Google Scholar 

  62. Siris ES, Chines AA, Altaian RD, et al. Risedronate in the treatment of Paget’s disease of bone: an open label, multicenter study. J Bone Miner Res 1998; 13(6): 1032–8

    Article  PubMed  CAS  Google Scholar 

  63. Grauer A, Knaus J, Seibel M, et al. Treatment of Paget’s disease of bone with the new bisphosphonates BM 21.0955 by intravenous bolus injection. J Bone Miner Res 1994; 9Suppl. l: S430

    Google Scholar 

  64. Arden-Cardone M, Siris ES, Lyles KW, et al. Antiresorptive effect of a single infusion of microgram quantities of zole-dronate in Paget’s disease of bone. Calcif Tissue Int 1997; 60: 415–8

    Article  Google Scholar 

  65. Garnero P, Gineyts E, Schaffer AV, et al. Measurement of urinary excretion of non-isomerized and beta-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget’s disease. Arthritis Rheum 1998; 41(2): 354–60

    Article  PubMed  CAS  Google Scholar 

  66. Adami S, Salvagno G, Guerrera G, et al. Treatment of Paget’s disease of bone with intravenous 4-amino-l-hydroxy-buthylidene-1,1-bisphosphonate. Calcif Tissue Int 1986; 39: 226–9

    Article  PubMed  CAS  Google Scholar 

  67. O’Doherty DP, McCloskey EV, Vasikaran S, et al. The effects of intravenous alendronate in Paget’s disease of bone. J Bone Miner Res 1995; 10: 1094–100

    Article  PubMed  Google Scholar 

  68. Rubens RD. Bone involvement in solid tumors. In: Bijvoet OLM, Fleisch HA, Canfield RE, et al., editors. Bisphosphonate on bones. Amsterdam: Elsevier, 1995: 337–47

    Google Scholar 

  69. Mundy GR, Martin TJ. Pathophysiology of skeletal complications of cancer. In: Mundy GR, Martin TJ, editors. Physiology and pharmacology of bone: handbook of experimental pharmacology. New York: Springer-Verlag, 1993: 641–71

    Chapter  Google Scholar 

  70. Martin TJ, Moseley JM, Gillespie MT. Parathyroid hormone-related protein: biochemistry and molecular biology. Crit Rev Biochem Mol Biol 1991; 26: 377–95

    Article  PubMed  CAS  Google Scholar 

  71. Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med 1997; 103: 134–45

    Article  PubMed  CAS  Google Scholar 

  72. Yoneda T. Mechanisms of preferential metastases of breast cancer to bone. Int J Oncol 1996; 9: 103–9

    PubMed  CAS  Google Scholar 

  73. Urwin GH, Persival RC, Harris S, et al. Generalized increase in bone resorption in carcinoma of the prostate. Br J Urol 1985; 57: 721–3

    Article  PubMed  CAS  Google Scholar 

  74. Goltzman D. Mechanisms of development of osteoblastic metastases. Cancer 1997; 80 Suppl.: 1581–7

    Article  PubMed  CAS  Google Scholar 

  75. Walls J, Ratcliffe WA, Howell A, et al. Response to intravenous bisphosphonate therapy in hypercalcaemic patients with and without bone metastases: the role of parathyroid hormone-related protein. Br J Cancer 1994; 70: 169–72

    Article  PubMed  CAS  Google Scholar 

  76. Bonjour JP, Philippe J, Guelpa G, et al. Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. Bone 1988; 9: 123–30

    Article  PubMed  CAS  Google Scholar 

  77. Adami S. Bisphosphonates in prostate carcinoma. Cancer 1997; Suppl. 80: 1674–9

    Google Scholar 

  78. Plosker GL, Goa KL. Clodronate: a review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs 1994; 47: 945–82

    Article  PubMed  CAS  Google Scholar 

  79. Kanis JA, Powles T, Paterson AHG, et al. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone 1996; 19(6): 663–67

    Article  PubMed  CAS  Google Scholar 

  80. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 1996; 335: 1785–91

    Article  PubMed  CAS  Google Scholar 

  81. Diel IJ, Solomayer EF, Costa S, et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998; 339: 357–63

    Article  PubMed  CAS  Google Scholar 

  82. Van der Pluijm G, Vloedgraven H, van Beek E, et al. Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 1996; 98: 698–705

    Article  PubMed  Google Scholar 

  83. Boissier S, Magnetto S, Frapport L, et al. Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to un-mineralized bone extracellular matrices. Cancer Res 1997; 57: 3890–4

    PubMed  CAS  Google Scholar 

  84. Adami S, Mian M. Clodronate therapy of metastatic bone disease in patients with prostatic carcinoma. Recent Results Cancer Res 1989; 116: 67–72

    Article  PubMed  CAS  Google Scholar 

  85. Pelger RCM, Hamdy NAT, Zwinderman AH, et al. Effect of the bisphosphonate olpadronate in patients with carcinoma of the prostate metastatic to the skeleton. Bone 1998; 22(4): 403–8

    Article  PubMed  Google Scholar 

  86. Wüster C, Shöter KH, Thiébaud D, et al. Methyl-pentylamino-propylidene-bisphosphonate (BM 21.0955): a new potent and safe bisphosphonate for the treatment of cancer-associated hypercalcemia. Bone Miner 1993; 22: 77–85

    Article  PubMed  Google Scholar 

  87. Ralston SH, Thiebaud D, Herrmann Z, et al. Dose-response study of ibandronate in the treatment of cancer-associated hypercalcemia. Br J Cancer 1997; 75(2): 295–300

    Article  PubMed  CAS  Google Scholar 

  88. Pecherstorfer M, Ludwig H, Schlosser K, et al. Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous bolus injection. J Bone Miner Res 1996; 11: 587–93

    Article  PubMed  CAS  Google Scholar 

  89. Blind E, Rave F, Meinel T, et al. Levels of parathyroid hormone-related protein (PTHrP) in hypercalcemia of malignancy are not lowered by treatment with the bisphosphonate BM 21.0955. Horm Metab Res 1993; 25: 40–4

    Article  PubMed  CAS  Google Scholar 

  90. Body JJ. Clinical research update: zoledronate. Cancer 1997; 80 Suppl.: 1699–701

    Article  PubMed  CAS  Google Scholar 

  91. Usui T, Oiso Y, Tomita A, et al. Pharmacokinetics of icandronate, a new bisphosphonate, in healthy volunteers and patients with malignancy-associated hypercalcemia. Int J Clin Pharmacol Ther 1997; 35(6): 239–44

    PubMed  CAS  Google Scholar 

  92. Pecherstorfer M, Herrmann Z, Body JJ, et al. Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 1996; 14(1): 268–76

    PubMed  CAS  Google Scholar 

  93. Coleman RE, Purohit OP, Black C, et al. Ibandronate: a well-tolerated new oral bisphosphonate for the treatment of bone metastases [abstract]. Breast 1995; 4: 236

    Article  Google Scholar 

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    Davide Gatti &  Silvano Adami

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Gatti, D., Adami, S. New Bisphosphonates in the Treatment of Bone Diseases. Drugs Aging 15, 285–296 (1999). https://doi.org/10.2165/00002512-199915040-00004

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