Discovery, Clinical Development, and Therapeutic Uses of Bisphosphonates

Annals of Pharmacotherapy - Tập 39 Số 4 - Trang 668-677 - 2005
Angelo A. Licata1
1Angelo A Licata MD PhD FACP, Consultant, Metabolic Bone Center; Research Director, Department of Endocrinology, The Cleveland Clinic Foundation, 1063 Kirtland Ln., Lakewood, OH 441071423, fax 216/445-1656

Tóm tắt

OBJECTIVE:

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates.

DATA SOURCES:

English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined.

STUDY SELECTION AND DATA EXTRACTION:

Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses.

DATA SYNTHESIS:

Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R1 and R2). The R1 side chain determines binding affinity to hydroxyapatite, and the R2 side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity.

CONCLUSIONS:

The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Từ khóa


Tài liệu tham khảo

10.1016/S0889-8529(02)00064-6

10.1016/S8756-3282(02)00817-7

10.1053/ctrv.2000.0210

10.1021/j150401a002

10.1152/ajplegacy.1962.203.4.671

10.1177/00220345720510021701

10.1016/S0001-2998(76)80033-5

10.1126/science.165.3899.1262

10.1007/BF02065192

10.1007/BF02547227

10.1111/j.1365-2362.1970.tb00591.x

10.1007/BF01935714

10.1007/BF02547219

10.1016/S0140-6736(69)92293-4

10.1007/PL00004164

10.1016/S8756-3282(98)00120-3

10.1016/S0889-8529(05)70014-1

Geddes AD, 1994, Bone and Mineral Research, 265

10.1172/JCI118722

10.1124/mol.61.5.1255

10.1002/1529-0131(200109)44:9<2201::AID-ART374>3.0.CO;2-E

10.1210/edrv.19.1.0325

10.1006/abbi.1999.1502

Dunford JE, 2001, J Pharmacol Exp Ther, 296, 235

10.1016/0009-9236(95)90245-7

10.1016/8756-3282(95)00445-9

10.1023/A:1011024200280

10.1016/S8756-3282(02)00841-4

10.1016/S8756-3282(01)00665-2

10.1046/j.1365-2125.1999.00035.x

Lin JH, 1991, Drug Metab Dispos, 19, 926

10.1172/JCI115539

Mitchell DY, 1997, Bone, 20, 100S

10.1177/00912709922007958

10.1359/jbmr.1997.12.10.1700

2003, Actonel (risedronate sodium)

10.2165/00002512-199915040-00004

10.1177/00912700022008928

2004, Zometa (zoledronic acid)

2003, Boniva (ibandronate sodium)

2004, Fosamax (alendronate sodium)

10.1046/j.1365-2125.2000.00135.x

10.1016/S0140-6736(96)07088-2

10.1001/jama.280.24.2077

10.1210/jcem.85.11.6953

10.1056/NEJMoa030897

10.1359/jbmr.2002.17.11.1988

10.1359/JBMR.040920

10.1016/S0002-9343(01)01124-X

10.1385/JCD:7:3:255

10.1002/sim.984

10.1056/NEJM200008313430902

10.1056/NEJM199807303390502

Siris E, 1996, J Clin Endocrinol Metab, 81, 961

10.1016/j.bone.2003.12.011

10.1016/S0002-9343(96)00227-6

10.1016/S8756-3282(96)00364-X

10.1016/S0002-9343(99)00062-5

10.1016/0002-9343(87)90487-6

10.1001/archinte.1991.00400030039007

10.1002/1097-0142(19940515)73:10<2527::AID-CNCR2820731013>3.0.CO;2-3

10.1056/NEJM199708073370603

10.1136/thx.53.5.351

Sebaldt RJ, 1999, J Rheumatol, 26, 1545

10.1359/JBMR.040325

10.1046/j.1365-2796.2003.01174.x

10.1210/jc.2003-022029

Miller P, 2004, J Bone Miner Res, 19, S94

10.1136/ard.62.10.969

10.1007/s00198-003-1425-0

10.1007/s00520-003-0477-1

10.1200/JCO.1992.10.1.134

Trombetti A, 1999, Rev Rhum Engl Ed, 66, 467

10.1007/s10067-003-0762-x

Ismail AA, 1997, J Rheumatol, 24, 2266

10.1007/BF02509539

10.4158/EP.7.6.423

10.1001/jama.282.14.1344

10.1007/s001980050010

10.1185/030079903125003125

10.1007/s00223-003-0042-4

10.1016/S8756-3282(02)00946-8

10.1007/s00223-004-0286-7

10.1056/NEJM200102013440503

10.1007/s00223-002-2011-8

10.1185/030079904125003566

10.1007/s00198-003-1401-8

10.1359/jbmr.2000.15.6.1006

10.1002/1529-0131(199911)42:11<2309::AID-ANR8>3.0.CO;2-K

10.1007/s002230001146

10.1136/pgmj.73.862.496

10.1016/8756-3282(95)00282-1

10.1002/art.1780380620

10.1002/jbmr.5650090505

10.1007/s001980170126

10.1200/JCO.2001.19.2.558

Rosen LS, 2001, Cancer J, 7, 377

10.1056/NEJMoa011807

2003, Physician's guide to prevention and treatment of osteoporosis

10.1002/1529-0131(200107)44:7<1496::AID-ART271>3.0.CO;2-5

10.1007/s00198-003-1502-4

Cramer J, 2004, (abstract). J Bone Miner Res, 19, S448

Recker R, 2004, J Bone Miner Res, 19, S172, 10.1359/jbmr.2004.19.1.172

10.1001/jama.288.15.1889

10.1007/s00198-002-1345-4

10.1016/j.bone.2003.12.013

10.1359/jbmr.2003.18.6.1051

Thông tin
Thông tin xuất bản

Annals of Pharmacotherapy

Tập 39 Số 4

668-677

Thông tin tác giả