The relative merits of anabolics versus anti-resorptive compounds: where our targets should be, and whether we are addressing them

Current Opinion in Pharmacology

Volumn 6, Issue 3, 2006, Pages 313-318

  Gasser, Jürg A ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; ANABOLIC AGENT; BALICATIB; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CALCIUM ANTAGONIST; CATHEPSIN K INHIBITOR; DENOSUMAB; ESTROGEN; IBANDRONIC ACID; MONOCLONAL ANTIBODY; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; PLACEBO; PROGESTERONE; RALOXIFENE; RELACATIB; RISEDRONIC ACID; STRONTIUM RANELATE; UNCLASSIFIED DRUG;

ADJUVANT THERAPY; BONE REMODELING; CANCELLOUS BONE; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; EXERCISE; FALLING; FRAGILITY FRACTURE; HIP FRACTURE; HORMONE SUBSTITUTION; HUMAN; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; POSTMENOPAUSE OSTEOPOROSIS; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; TRABECULAR BONE; VERTEBRA FRACTURE;

ACCIDENTAL FALLS; ANTIBODIES, MONOCLONAL; BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; BONE REGENERATION; BONE RESORPTION; CATHEPSIN K; CATHEPSINS; DIPHOSPHONATES; EXERCISE THERAPY; FRACTURES, BONE; HUMANS; OSTEOPOROSIS; RANK LIGAND; TERIPARATIDE;

EID: 33646353183     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2006.03.004     Document Type: Review

References (44)

1. Reginster J.Y., Sarlet N., and Lecart M.P. Fractures in osteoporosis: the challenge for the new millennium. Osteoporos Int 16 (2005) S1-S3
2. Neer R.M., Arnaud C.D., Zanchetta J.R., Prince R., Gaich G.A., Reginster J.Y., Hodsman A.B., Eriksen E.F., Ish-Shalom S., Genant H.K., et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344 (2001) 1434-1441
3. Kaufman J.M., Orwoll E., Goemare S., San Martin J., Hossain A., Dalsky G.P., Lindsay R., and Mitlak B.H. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 16 (2005) 510-516
4. Meunier P.J., Roux C., Seeman E., Ortolani S., Badurski J.E., Spector T.D., Cannata J., Balogh A., Lemmel E.M., Pors-Nielsen S., et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350 (2004) 459-468
5. Cosman F. The prevention and treatment of osteoporosis: a review. MedGenMed 7 (2005) 73
6. McCarus D.C. Fracture prevention in postmenopausal osteoporosis: a review of treatment options. Obstet Gynecol Surv 61 (2006) 39-50
7. Reid I.R., Brown J.P., Burckhardt P., Horowitz Z., Richardson P., Trechsel U., Widmer A., Devogelaer J.P., Kaufman J.M., Jaeger P., et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346 (2002) 653-661
8. Bekker P.J., Holloway D.L., Rasmussen A.S., Murphy R., Martin S.W., Leese P.T., Holmes G.B., Dunstan C.R., and Depaoli A.M. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19 (2004) 1059-1066. This paper provided the first evidence that injection of human monoclonal antibody to RANKL (denosumab) could lead to long-term suppression of bone resorption (up to six months) in patients. First evidence for proof-of-concept of this novel approach.
9. McClung M.R., Lewiecki E.M., Cohen S.B., Bolognese M.A., Woodson G.C., Moffett A.H., Peacock M., Miller P.D., Lederman S.N., Chesnut C.H., et al., for the AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354 (2006) 821-831. First publication of two-year BMD data for denosumab, demonstrating rapid onset and sustained anti-resorptive efficacy of this novel anti-resorptive therapy when given every six months.
10. Geusens P., and Reid D. Newer drug treatments: their effects on fracture prevention. Best Pract Res Clin Rheumatol 19 (2005) 983-989
11. Black D.M., Cummings S.R., Karpf D.B., Cauley J.A., Thompson D.E., Nevitt M.C., Bauer D.C., Genant H.K., Haskell W.L., Marcus R., et al., Fracture Intervention Trial Research Group. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348 (1996) 1535-1541
12. McClung M.R., Geusens P., Miller P.D., Zippel H., Bensen W.G., Roux C., Adami S., Fogelman I., Diamond T., Eastell R., and for the Hip intervention Program Study Group. Effect of risedronate on the risk fracture in elderly women. N Engl J Med 344 (2001) 333-340
13. Reginster J.Y., Minne H.W., Sorensen O.H., Hooper M., Roux C., Brandi M.L., Lund B., Ethgen D., Pack S., Roumagnac I., and Eastell R. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 11 (2000) 83-91
14. Watts N.B., Josse R.G., Hamdy R.C., Hughes R.A., Manhart M.D., Barton I., Calligeros D., and Felsenberg D. Risedronate prevents new vertebral fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 88 (2003) 542-549
15. Manson J.E., Hsia J., Johnson K.C., Rossouw J.E., Assaf A.R., Lasser N.L., Trevisan M., Black H.R., Heckbert S.R., Detrano R., et al. Womens health initiative investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 349 (2003) 523-534
16. Ettinger B., Black D.M., Mitlak B.H., Knickerbocker R.K., Nickelsen T., Genant H.K., Christiansen C., Delmas P.D., Zanchetta J.R., Stakkestad J., et al. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators: Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with Raloxifene: results from a 3-year randomized clinical trial. J Am Med Assoc 282 (1999) 637-645 Erratum in: J Am Med Assoc 1999, 282:2124
17. Chesnut III C.H., Silverman S., Andriano K., Genant H., Gimona A., Harris S., Kiel D., LeBoff M., Maricic M., Miller P., et al., for the PROOF Study Group. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence. Am J Med 109 (2000) 267-276
18. Weinans H: Architectural changes independent of bone mineral in osteoporosis. 32nd International Sun Valley Hard Tissue Workshop, 2002.
19. Bell K.L., Loveridge N., Reeve J., Thomas C.D., Feik S.A., and Clement J.G. Super-osteons (remodeling clusters) in the cortex of the femoral shaft: influence of age and gender. Anat Rec 264 (2001) 378-386
20. Burr D.B., Hirano T., Turner C.H., Hotchkiss C., Brommage R., and Hock J.M. Intermittently administered human parathyroid hormone (1-34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 16 (2001) 157-165
21. Burr D.B. Does early PTH treatment compromise bone strength? The balance between remodeling, porosity, bone mineral, and bone size. Curr Osteoporos Rep 3 (2005) 19-24
22. Zanchetta J.R., Bogado C.E., Ferreti J.L., Wang O., Wilson M.G., Sato M., Gaich G.A., Dalsky G.P., and Myers S.L. Effects of teriparatide recombinant human parathyroid hormone (1-34) on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 18 (2003) 539-543
23. Lindsay R., Cosman F., Zhou H., Bostrom M.P., Shen V.W., Cruz J.D., Nieves J.W., and Dempster D.W. A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest biopsy: early actions of teriparatide. J Bone Miner Res 21 (2006) 366-373. First direct evidence in humans, from iliac crest biopsies based on tetracycline labelling, that PTH can directly activate bone formation (modelling drifts) independent of bone resorption. Although this had already been suggested by data from animal studies, this idea was refused by clinicians.
24. Dobnig H., and Turner R.T. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136 (1995) 3632-3638
25. Bradbeer J.N., Arlot M.E., Meunier P.J., and Reeve J. Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone. Clin Endocrinol (Oxf) 37 (1992) 282-289
26. Jiang Y., Zhao J.J., Mitlak B.H., Wang O., Genant H.K., and Eriksen E.F. Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 18 (2003) 1932-1941
27. Dempster D.W., Cosman F., Kurland E.S., Zhou H., Nieves J., Woelfert L., Shane E., Plavetic K., Muller R., Bilezikian J., et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16 (2001) 1846-1853
28. Oxlund H., Ejersted C., Andreassen T.T., Torring O., and Nilsson M.H. Parathyroid hormone (1-34) and (1-84) stimulate cortical bone formation both from periosteum and endosteum. Calcif Tissue Int 53 (1993) 394-399
29. Uusi-Rasi K., Semanick L.M., Zanchetta J.R., Bogado C.E., Eriksen E.F., Sato M., and Beck T.J. Effects of teriparatide [rhPTH (1-34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36 (2005) 948-958
30. Morko J., Kiviranta R., Hurme S., Rantakokko J., and Vuorio E. Differential turnover of cortical and trabecular bone in transgenic mice overexpressing cathepsin K. Bone 36 (2005) 854-865. The paper suggests that overexpression of cathepsin K can have different envelope-specific effects in cancellous and cortical bone in mice. Interestingly, the results published (in abstract form only) by two independent groups (Stroup and Jerome) suggest that cathepsin K inhibitors may exert positive effects on the mineralising surface at the periosteal envelope, in line with data published by Morko.
31. James I.E., Marquis R.W., Blake S.M., Hwang S.M., Gress C.J., Ru Y., Zembryki D., Yamashita D.S., McQueney M.S., Tomaszek T.A., et al. Potent and selective cathepsin L inhibitors do not inhibit human osteoclast resorption in vitro. J Biol Chem 276 (2001) 11507-11511
32. Deaton D.N., and Tavares F.X. Design of cathepsin K inhibitors for osteoporosis. Curr Top Med Chem 5 (2005) 1639-1675. Excellent review about cathepsin K, its function and the available drugs targeting this protease.
33. Gowen M., Lazner F., Dodds R., Kapadia R., Feild J., Tavaria M., Bertoncello I., Drake F., Zavarselk S., Tellis I., et al. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 14 (1999) 1654-1663
34. Stroup G., Jerome C., Yamashita D.S., and Kumar S. Histomorphometric and biochemical evidence for a cortical bone-forming effect of a cathepsin K inhibitor in ovariectomized cynomolgus monkeys [abstract]. J Bone Miner Res 20 Suppl 1 (2005) S80
35. Jerome C., Missbach M., and Gamse R. AAE581, a novel cathepsin K inhibitor, protects against ovariectomy-induced bone loss in non-human primates, in part by stimulation of periosteal bone formation [abstract]. J Bone Miner Res 20 Suppl 1 (2005) S46
36. Boyle W.J. Osteoclast differentiation and activation. Nature 423 (2003) 337-342
37. Dunstan C.R., and DePaoli A.M. A single-dose placebo controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19 (2004) 1059-1066
38. Cohen S.B., Lewiecki E.M., Liu Y., Zack D.J., and Fitzpatrick L.A. Phase 2 study of AMG 162 in postmenopausal women: subanalysis and supplemental safety [abstract]. J Bone Miner Res 20 Suppl 1 (2005) S295
39. Hui S., Slemenda C.W., and Johnstone C.C. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 81 (1988) 1804-1809
40. Cummings S.R., and Melton L.J. Epidemiology and outcomes of osteoporotic fractures. Lancet 359 (2002) 1761-1767
41. Roubenoff R. Origins and clinical relevance of sarcopenia. Can J Appl Physiol 26 (2001) 78-89
42. Walsh M.C., Hunter G.R., and Livingstone M.B. Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int 17 (2005) 61-67. Great source of information about sarcopenia and its clinical importance.
43. Runge M., Rittweger J., Russo C.R., Schiessl H., and Felsenberg D. Is muscle power output a key factor in the age-related decline in physical performance? A comparison of muscle cross section, chair-rising test and jumping power. Clin Physiol Funct Imaging 24 (2004) 335-340. Description of sarcopenia as an important risk factor for fractures and its relationship to menopausal status and osteopenia.
44. Thompson K.R., Mikesky A.E., Bahamonde R.E., and Burr D.B. Effects of physical training on proprioception in older women. J Musculoskelet Neuronal Interact 3 (2003) 223-231