Novel therapies for osteoporosis

Expert Opinion on Investigational Drugs

Volumn 12, Issue 4, 2003, Pages 611-621

  Biskobing, Diane M ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bisphosphonates; Cathepsin; Integrin receptor inhibitors; Isoflavones; K inhibitors; NON NSAIDs; Osteoporosis; PTH; SERMs; Src inhibitors; Statins; Strontium

Indexed keywords

ANABOLIC AGENT; ARZOXIFENE; BAZEDOXIFENE; BISPHOSPHONIC ACID DERIVATIVE; ENZYME INHIBITOR; FLUINDOSTATIN; FLURBIPROFEN 4 NITROXYBUTYL ESTER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IBANDRONIC ACID; INTEGRIN RECEPTOR BLOCKING AGENT; ISOFLAVONE DERIVATIVE; LASOFOXIFENE; MDL 103323; MINODRONIC ACID; NONSTEROID ANTIINFLAMMATORY AGENT; OSTEOPROTEGERIN; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; PRAVASTATIN; PROTEIN TYROSINE KINASE INHIBITOR; SB 357114; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SIMVASTATIN; STRONTIUM; STRONTIUM RANELATE; TIBOLONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZOLEDRONIC ACID;

BONE DENSITY; BONE MINERAL; BONE TURNOVER; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; DRUG RESEARCH; DRUG TOLERABILITY; EUROPE; FRAGILITY FRACTURE; HUMAN; NONHUMAN; OSTEOPOROSIS; REVIEW; VAGINA BLEEDING;

ANABOLIC AGENTS; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ENZYME INHIBITORS; ESTROGENS; HUMANS; OSTEOPOROSIS;

EID: 0037399385     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.4.611     Document Type: Review

References (83)

1. JEPPESEN PB, HARTMANN B, THULESEN J et al.: Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology (2001) 120:806-815.
2. HADERSLEV KV, JEPPESEN PB, HARTMANN B et al.: Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon. Scand. J. Gastroenterol. (2002) 37:392-398.
3. ALBRIGHT F, AUB JC, BAUER W: Hyperparathyroidism: a common and polymorphic condition as illustrated by seventeen proven cases from one clinic. JAMA (1934) 102:1276-1287.
4. RUBIN MR, COSMAN F, LINDSAY R, BILEZIKIAN JP: The anabolic effects of parathyroid hormone. Osteop. Internat. (2002) 13:267-277.
5. BAUER W, AUB JC, ALBRIGHT F: Studies of calcium and phosphorous metabolism. V. A study of the bone trabeculae as a readily reversible supplementary of calcium. J. Exp. Med. (1929) 49:145-161.
6. TAM CS, HEERSCHE JN, MURRAY TM, PARSONS JA: Parathyhroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continous administration. Endocrinology (1982) 110:506-512.
7. NEER RM, ARNAUD CD, ZANCHETTE JR et al.: Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. (2001) 344:1434-1441.
8. RITTMASTER RS, BOLOGNESE M, ETTINGER MP et al.: Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J. Clin. Endocrin. Metab. (2000) 85:2129-2134.
9. CANALIS E, HOTT M, DELOFFRE P, TSOUDEROS Y, MARIE PJ: The divalen strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone (1996) 18:517-523.
10. MARIE PJ, HOTT M, MODROWSKI D et al.: An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J. Bone Miner. Res. (1993) 8:607-615.
11. BOIVIN G, DELOFFRE P, PERRAT B et al.: Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J. Bone Miner. Res. (1996) 11:1302-1311.
12. MEUNIER PJ, SLOSMAN DO, DELMAS PD et al.: Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis - a 2-year randomized placebo controlled trial. J. Clin. Endocrinol. Metab. (2002) 87:2060-2066.
13. REGINSTER JY, DEROISY R, DOUGADOS M et al.: Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial. Osteoporos. Int. (2002) 13:925-931.
14. HENDRIX SL, MCNEELEY SG: Effect of selective estrogen receptor modulators on reproductive tissues other than endometrium. Ann. NY Acad. Sci. (2001) 949:243-250.
15. SATO M, TURNER CH, WANG T et al.: LY353381.HCl: a novel raloxifene analog with improved SERM potency and efficacy in vivo. J. Pharm. Exp. Ther. (1998) 287:1-7.
16. SATO M, ZENG GQ, ROWLEY E, TURNER CH: LY353381-HCl: an improved benzothiophene analog with bone efficacy comlementary to parathyroid hormone (1-34). Endocrinology (1998) 139:4642-4651.
17. SUH N, GLASEBROOK AL, PALKOWITZ AD et al.: Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer. Cancer Res. (2001) 61:8412-8415.
18. RONKIN S, CLARKE L, BOUDES P, CONSTANTINE B: TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose related fashion. J. Bone Miner. Res. (2001) 16:S413.
19. YLIKORKALA NO: Data presented at 2002 North American Menopause Society. Meeting of North American Menopause Society, Chicago, IL, USA (2002).
20. KE HZ, PARALKAR VM, GRASSER WA et al.: Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus, and body composition in rat models. Endocrinology (1998) 139:2068-2076.
21. MOFFETT A: Emerging data and experience with lasofoxifene: highlights from clinical trials. Symposium at International Osteoporosis Foundation - World Congress on Osteoporosis, Lisbon, Portugal (2002).
22. CHAVASSIEUX P, GARNERO P, DUBOEUF F et al.: Effects of a new selective estrogen receptor modulator (MDL 103,323) on cancellous and cortical bone in ovariectomized ewes: a biochemical, histomorphometric, and densitometric study. J. Bone Miner. Res. (2001) 16:89-96.
23. AMMANN P, BOURRIN S, BONJOUR JP, MEYER JM, RIZZOLI R: The new selective estrogen receptor modulator MDL 103,323 increases bone mineral density and bone strength in adult ovariectomized rats. Osteoporos. Int. (1999) 10:376.
24. BOURRIN S, AMMANN P, BONJOUR JP, RIZZOLI R: Recovery of proximal tibia bone mineral density and strength, but not cancellous bone architecture, after long-term bisphosphonate or selective estrogen receptor modulator therapy in aged rats. Bone (2002) 30:195-200.
25. ALEXANDERSEN P, RIIS BJ, STAKKESTAD JA, DELMAS PD, CHRISTIANSEN C: Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy. J. Clin. Endocrin. Metab. (2001) 86:755-760.
26. MODELSKA K, CUMMINGS S: Tibolone for postmenopausal women: systematic review of randomized trials. J. Clin. Endocrin. Metab. (2002) 87:16-23.
27. GALLAGHER JC, BAYLINK DJ, FREEMAN R, MCCLUNG MR: Prevention of bone loss with tibolone in postmenopausal women: results of two randomized double-blind, placebo-controlled, dose-finding studies. J. Clin. Endocrin. Metab. (2001) 86:4717-4726.
28. RYMER J, ROBINSON J, FOGELMAN I: Effects of 8 years of treatment with tibolone 2.5 mg daily on postmenopausal bone loss. Osteoporos. Int. (2001) 12:478-483.
29. STUDD J, ARNALA I, KICOVIC PM et al.: A randomized study of tibolone on bone mineral density in osteoporotic postmenopausal women with previous fractures. Obstet. Gynecol. (1998) 92:574-579.
30. MILNER M, HARRISON RF, GILLIGAN E, KELLY A: Bone density changes during two years treatment with tibolone or conjugated estrogens and norgestrel, compared with untreated controls in postmenopausal women. Menopause (2000) 7:327-333.
31. HAMMAR M, CHRISAU S, NATHORST-BÕÕS J, RUD T, GARRE K: A double-blind, randomised trial comparing the effects of tibolone and continous combined hormone replacemnt therapy in postmenopausal women with menopausal symptoms. Br. J. Obstet. Gynaec. (1998) 105:904-911.
32. BERNING B, VAN KUIJK C, COELINGH BENNINK HJT, FAUSER BCJM: Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women. Maturitas (2000) 35:81-88.
33. GARNERO P, JAMIN C, BENHAMOU CL, PELISSIER C, ROUX C: Effects of tibolone and combined 17beta-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial. Hum. Reprod. (2002) 17:2748-2753.
34. BARNES S, PETERSON TG: Biochemical targets of the isoflavone genistein in tumor cell lines. Proc. Soc. Exp. Biol. Med. (1995) 208:103-108.
35. MAZUR W, ADLERCREUTZ H: Overview of naturally occurring endocrine-active substances in the human diet in relation to human health. Nutrition (2000) 16:654-658.
36. SOMEKAWA Y, CHIGUCHI M, ISHIBASHI T, ASO T: Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet. Gynecol. (2001) 97:109-115.
37. MEI J, YEUNG SSC, KUNG AWC: High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premeonapusal women. J. Clin. Endocrin. Metab. (2001) 86:5217-5221.
38. ADAMI S, BUFALINO L, CERVETTI R et al.: Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteop. Internat. (1997) 7:119-125.
39. GENNARI C, AGNUSDEI D, CREPALDI G et al.: Effect of ipriflavone - a synthetic derivative of natural isoflavones-on bone mass loss in the early years after menopause. Menopause (1998) 5:9-15.
40. CLIFTON-BLIGH PB, BABER RJ, FULCHER GR, NERY ML, MORETON T: The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause (2001) 8:259-265.
41. ALEXANDERSEN P, TOUSSAINT A, CHRISTIANSEN C et al.: Ipriflavone in the treatment of postmenopausal osteoporosis. JAMA (2001) 285:1482-1488.
42. DUNFORD JE, THOMPSON K, COXON FP et al.: Strucuture-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J. Pharm. Exp. Ther. (2001) 296:235-242.
43. SZABO CM, MARTIN MB, OLDFIELD E: An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs. J. Med. Chem. (2002) 45:2894-2903.
44. RAVN P, CLEMMESEN B, RIIS BJ, CHRISTIANSEN C: The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopuasal osteopororosis: a 1-year, randomized, double-bline, placebo-controlled dose-finding study. Bone (1996) 19:527-533.
45. RIIS BJ, ISE J, VON STEIN T, BAGGER Y, CHRISTIANSEN C: Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis. J. Bone Miner. Res. (2001) 16:1871-1878.
46. MORII H, NISHIZAWA Y, TAKETANI Y et al.: A randomized controlled trial with ONO-5920 (minodronate/YM529) in Japanese patients with postmenopausal osteoporosis. J. Bone Miner. Res. (2002) 17:M342.
47. 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.
48. PECHERSTORFER M, LOHO N, MIRZAI S et al.: Tri-monthly intravenous injections of ibandronate (2 mg) for treatment of postmenopausal osteoporosis. J. Bone Miner. Res. (2001) 16S1:S406.
49. FAHRLEITNER A, PRENNER G, LEB G et al.: Combination therapy with ibandronate and calcitriol is effective in patients following liver transplantation. J. Bone Miner. Res. (2001) 16S1:S287.
50. SIMONET WS, LACEY DL, DUNSTAN CR et al.: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell (1997) 89:309-319.
51. TSUDA E, GOTO M, MOCHIZUKI Y et al.: Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem. Biophys. Res. Commun. (1997) 234:137-142.
52. LACEY DL, TIMMS E, TAN HL et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell (1998) 93:165-176.
53. YASUDA H, SHIMA N, NAKAGAWA N et al.: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA (1998) 95:3597-3602.
54. BUCAY N, SAROSI I, DUNSTAN CR et al.: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. (1998) 12:1260-1268.
55. BEKKER PJ, HOLLOWAY D, NAKANISHI A et al.: The effect of a single dose of osteoprotegerin in postmenopausal women. J. Bone Miner. Res. (2001) 16:348-360.
56. LARK MW, STROUP GB, JAMES IE et al.: A potent small molecule, nonpeptide inhibitor of cathepsin K (SB 331750) prevents bone matrix resorption in the ovariectomized rat. Bone (2002) 30:746-753.
57. STROUP GB, LARK MW, VEBER DF et al.: Potent and selective inhibition of human cathepsin K leads to inhibition of bone resorption in vivo in a nonhuman primate. J. Bone Miner. Res. (2001) 16:1739-1746.
58. 3 Integrin antagonists as inhibitors of bone resorption. Expert Opin. Invest. Drugs (2000) 9:1281-1291.
59. MOUSA SA: Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications. Curr. Opin. Chem. Biol. (2002) 6:534-541.
60. MILLER WH, BONDINELL WE, COUSINS RD et al.: Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model. Bioorg. Med. Chem. Lett. (1999) 9:1807-1812.
61. LARK MW, STROUP GB, HWANG SM et al.: Design and characterization of orally active Arg-Gly-Asp epetidomimetic vitronectin receptor antagonist SB 265123 for prevedtion of bone loss in osteoporosis. J. Pharm. Exp. Therap. (1999) 291:612-617.
62. 2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and - independent mechanism in rat osteoblasts in vitro. J. Biol. Chem. (1999) 274:1776-1782.
63. VAN 'T HOF RJ, ARMOUR KJ, SMITH LM et al.: Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. Proc. Natl. Acad. Sci. USA (2000) 97:7993-7998.
64. AKATSU T, TAKAHASHI N, UDAGAWA N et al.: Role of prostaglandins in interleukin-1-induced bone resorption in mice in vitro. J. Bone Miner. Res. (1991) 6:183-190.
65. MORTON DJ, BARRETT CE, SCHNEIDER DL: Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study. J. Bone Miner. Res. (1998) 13:1924-1931.
66. MACINTYRE I, ZAIDI M, TOWHIDUL ALAM ASM et al.: Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP. Proc. Natl. Acad. Sci. USA (1991) 88:2936-2940.
67. WIMALAWANSA S, CHAPA T, FANG L et al.: Frequency-dependent effect of nitric oxide donor nitroglycerin on bone. J. Bone Miner. Res. (2000) 15:1119-1125.
68. ARMOUR KJ, VAN 'T HOF RJ, ARMOUR KE et al.: Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone loss in vivo by flurbiprogen nitroxybutylester (HCT-1026). Arthritis Rheum. (2001) 44:2185-2192.
69. SHAKESPEARE W, YANG M, BOHACEK R et al.: Structure-based design of an osteoclast-selective, nonpeptide Src homology 2 inhibitor with in vivo antiresorptive activity. Proc. Natl. Acad. Sci. USA (2000) 97:9373-9378.
70. MISSBACH M, JESCHKE M, FEYE J et al.: A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of tis major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone (1999) 24:437-449.
71. MUNDY GR, GARRETT R, HARRIS S et al.: Stimulation of bone formation in vitro and in rodents by statins. Science (1999) 286:1946-1949.
72. CHUNG YS, LEE MD, LEE SK, KIM HM, FITZPATRICK LA: HMG-CoA Reductase inhibitors increase BMD in Type 2 diabetes mellitus patients. J. Clin. Endocrin. Metab. (2000) 85:1137-1142.
73. EDWARDS CJ, HART DJ, SPECTOR TD: Oral statins and increased bone mineral density in postmenopausal women. Lancet (2000) 355:2218-2219.
74. SIROLA J, HONKANEN R, KROEGER H et al.: Relation of statin use and bone loss: a prospective population-based cohort study in early postmenopausal women. Osteoporos. Int. (2002) 13:537-541.
75. CAULEY JA, JACKSON R, PETTINGER M et al.: Statin use and bone mineral density (BMD) in older women: the women's health initiative observational study (WHI-OS). J. Bone Miner. Res. (2000) 15S1:S155.
76. CHAN KA, ANDRADE SE, BOLES M et al.: Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet (2000) 355:2185-2188.
77. WANG PS, SOLOMON DH, MOGUN H, AVORN J: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA (2000) 283:3211-3216.
78. MEIER CR, SCHLIENGER RG, KRAENZLIN ME, SCHLEGEL B, JICK H: HMG-CoA reductase inhibitors and the risk of fractures. JAMA (2000) 283:3205-3210.
79. VAN STAA TP, WEGMAN S, DE VRIES F, LEUFKENS B, COOPER C: Use of statins and risk of fractures. JAMA (2001) 285:1850-1855.
80. REID IR, HAGUE W, EMBERSON J et al.: Effect of pravastatin on frequency of fracture in the LIPID study: secondary analysis of a randomised controlled trial. Lancet (2001) 357:509-512.
81. LACROIX AZ, CAULEY JA, JACKSON R et al.: Does statin use reduce risk of fracture in postmenopausal women? J. Bone Miner. Res. (2000) 15S1:S155.
82. BAUER DC, BLACK DM, VAN DER KLIFT M: Statin use and fracture: a meta-analysis of 8 observational studies. Bone (2001) 28S:S89.
83. MUNDY GR: Statins and their potential for osteoporosis. Bone (2001) 29:495-497.