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Osteoporosis International

Erschienen in:

01.03.2016 | Editorial

Cancel the denosumab holiday

verfasst von: M. R. McClung

Erschienen in: Osteoporosis International | Ausgabe 5/2016

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Excerpt

Denosumab, a fully human IgG2 anti-RANK ligand antibody, quickly and substantially inhibits bone remodeling [1]. As expected by the pharmacology of denosumab, this inhibition of remodeling is completely reversible upon stopping treatment [2]. In clinical trials, discontinuing therapy after 2 years results in a rapid rebound in bone turnover markers, raising concern about whether that high remodeling rate and consequent rapid bone loss that occurs has clinical relevance beyond a simple waning of the treatment benefit [3, 4]. Despite these concerns, many patients stop denosumab therapy, sometimes upon the advice of their physicians, especially in preparation for invasive dental procedures [5‐7]. Three recent reports have described five patients in whom denosumab treatment was stopped because substantial gains on bone mineral density (BMD) had been achieved and who then experienced vertebral fractures within the first several months after discontinuing therapy. These cases re-focus our attention on the concern about a rebound in fracture risk and make it clear that a “holiday” from denosumab therapy is not justified in patients with osteoporosis [8‐10]. …

Suresh E, Abrahamsen B (2015) Denosumab: a novel antiresorptive drug for osteoporosis. Cleve Clin J Med 82(2):105–114PubMed

Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19(12):1059–1066CrossRefPubMed

Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San MJ (2008) Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43(2):222–229CrossRefPubMed

Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 96(4):972–980CrossRefPubMed

Slim L. Dental strategies for osteoporosis drugs. http://www.rdhmag.com/articles/print/volume-34/issue-8/columns/dental-strategies-for-osteoporosis-drugs.html

Malan J, Ettinger K, Naumann E, Beirne OR (2012) The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 114(6):671–676CrossRef

O’Halloran M, Boyd NM, Smith A (2014) Denosumab and osteonecrosis of the jaws—the pharmacology, pathogenesis and a report of two cases. Aust Dent J 59(4):516–519CrossRefPubMed

Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O (2015) Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int. doi:10.1007/s00198-015-3380-y

Popp AW, Zysset PK, Lippuner K (2015) Rebound-associated vertebral fractures after discontinuation of denosumab—from clinic and biomechanics. Osteoporos Int. doi:10.1007/s00198-015-3458-6 PubMed

10.

Anastasilakis AD, Makras P (2015) Multiple clinical vertebral fractures following denosumab discontinuation. Osteoporos Int. doi:10.1007/s00198-015-3459-5

11.

Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765CrossRefPubMed

12.

Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C, Denosumab HALT Prostate Cancer Study Group (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361(8):745–755CrossRefPubMedPubMedCentral

13.

Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF, Austrian Breast and Colorectal Cancer Study Group (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386(9992):433–443CrossRefPubMed

14.

Papapoulos S, Lippuner K, Roux C, Lin CJ, Kendler DL, Lewiecki EM, Brandi ML, Czerwiński E, Franek E, Lakatos P, Mautalen C, Minisola S, Reginster JY, Jensen S, Daizadeh NS, Wang A, Gavin M, Libanati C, Wagman RB, Bone HG (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26(12):2773–2783CrossRefPubMedPubMedCentral

15.

Ferrari S, Adachi JD, Lippuner K, Zapalowski C, Miller PD, Reginster JY, Törring O, Kendler DL, Daizadeh NS, Wang A, O’Malley CD, Wagman RB, Libanati C, Lewiecki EM (2015) Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. Osteoporos Int 26(12):2763–2771CrossRefPubMedPubMedCentral

16.

Lewiecki EM, Miller PD, Harris ST, Bauer DC, Davison KS, Dian L, Hanley DA, McClung MR, Yuen CK, Kendler DL (2014) Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis. J Clin Densitom 17(4):490–495CrossRefPubMed

17.

Silverman SL, Siris E, Kendler DL, Belazi D, Brown JP, Gold DT, Lewiecki EM, Papaioannou A, Simonelli C, Ferreira I, Balasubramanian A, Dakin P, Ho P, Siddhanti S, Stolshek B, Recknor C (2015) Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study. Osteoporos Int 26(1):361–372CrossRefPubMedPubMedCentral

18.

Papaioannou A, Khan A, Belanger A, Bensen W, Kendler D, Theoret F, Amin M, Brekke L, Erdmann M, Walker V, Adachi JD (2015) Persistence with denosumab therapy among osteoporotic women in the Canadian patient-support program. Curr Med Res Opin 31(7):1391–1401CrossRefPubMed

19.

Karlsson L, Lundkvist J, Psachoulia E, Intorcia M, Ström O (2015) Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. Osteoporos Int 26(10):2401–2411CrossRefPubMedPubMedCentral

20.

Hadji P, Papaioannou N, Gielen E, Feudjo Tepie M, Zhang E, Frieling I, Geusens P, Makras P, Resch H, Möller G, Kalouche-Khalil L, Fahrleitner-Pammer A (2015) Persistence, adherence, and medication-taking behavior in women with postmenopausal osteoporosis receiving denosumab in routine practice in Germany, Austria, Greece, and Belgium: 12-month results from a European non-interventional study. Osteoporos Int 26(10):2479–2489CrossRefPubMedPubMedCentral

21.

Lewiecki EM, Cummings SR, Cosman F (2013) Treat-to-target for osteoporosis: is now the time? J Clin Endocrinol Metab 98(3):946–953CrossRefPubMed

22.

Johansson H, Odén A, Kanis JA, McCloskey EV, Morris HA, Cooper C, Vasikaran S (2014) IFCC-IOF joint working group on standardisation of biochemical markers of bone turnover. A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif Tissue Int 94(5):560–567CrossRefPubMed

23.

Dufresne TE, Chmielewski PA, Manhart MD, Johnson TD, Borah B (2003) Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography. Calcif Tissue Int 73(5):423–432CrossRefPubMed

24.

McClung M, Lewiecki EM, Ho P-R, Michael Bolognese M, Wang A, Geller M, O’Malley C, Wagman RB, Miller P (2013) OR10-6: management trends after 8 years of denosumab: follow-up after a one-year observational phase of the phase 2 extension study. (abstract). Endo Society

25.

Brown JP, Roux C, Törring O, Ho PR, Beck Jensen JE, Gilchrist N, Recknor C, Austin M, Wang A, Grauer A, Wagman RB (2013) Discontinuation of denosumab and associated fracture incidence: analysis from the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial. J Bone Miner Res 28(4):746–752CrossRefPubMedPubMedCentral

26.

Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, Wu M, Kaur A, Lombardi A (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, doubleblind, placebo-controlled trial. Ann Intern Med 137(11):875–883CrossRefPubMed

27.

Wasnich RD, Bagger YZ, Hosking DJ, McClung MR, Wu M, Mantz AM, Yates JJ, Ross PD, Alexandersen P, Ravn P, Christiansen C, Santora AC 2nd, Early Postmenopausal Intervention Cohort Study Group (2004) Changes in bone density and turnover after alendronate or estrogen withdrawal. Menopause 11(6 Pt 1):622–630CrossRefPubMed

28.

Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, Alendronate Phase III Osteoporosis Treatment Study Group (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350(12):1189–1199CrossRefPubMed

29.

Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RL, Tan M, Ruzycky ME, Su G, Eastell R (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27(2):243–254CrossRefPubMedPubMedCentral

30.

Neele SJ, Evertz R, De Valk-De Roo G, Roos JC, Netelenbos JC (2002) Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone 30(4):599–603CrossRefPubMed

31.

Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, Burnett-Bowie SA, Neer RM, Leder BZ (2013) Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382(9886):50–56CrossRefPubMedPubMedCentral

32.

Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, Reginster JY, Stepan JJ, Myers SL, Mitlak BH (2004) Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 164(9):2024–2030CrossRefPubMed

33.

Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, Verbruggen N, Hustad CM, DaSilva C, Petrovic R, Santora AC, Ince BA, Lombardi A (2011) Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res 26(2):242–251CrossRefPubMed

34.

Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, Le Bailly De Tilleghem C, Dasilva C, Rosenberg E, Leung A (2012) Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res 27(11):2251–2258CrossRefPubMed

35.

The Writing Group for the PEPI Trial (1996) Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 276(17):1389–1396CrossRef

36.

Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR (1995) Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 122(1):9–16CrossRefPubMed

37.

Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB, Women’s Health Initiative Investigators (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290(13):1729–1738CrossRefPubMed

38.

Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S, Women’s Health Initiative Steering Committee (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291(14):1701–1712CrossRefPubMed

39.

Lindsay R, Hart DM, MacLean A, Clark AC, Kraszewski A, Garwood J (1978) Bone response to termination of oestrogen treatment. Lancet 1(8078):1325–1327CrossRefPubMed

40.

Christiansen C, Christiansen MS, Transbol I (1981) Bone mass in postmenopausal women after withdrawal of oestrogen/gestagen replacement therapy. Lancet 28(8228):459–461CrossRef

41.

Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E, PEPI Safety Follow-Up Study (PSFS) Investigators (2002) Bone mass response to discontinuation of long-term hormone replacement therapy: results from the postmenopausal estrogen/progestin interventions (PEPI) safety follow-up study. Arch Intern Med 162(6):665–672CrossRefPubMed

42.

Gallagher J, Rapuri PB, Haynatzki G, Detter JR (2002) Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab 87(11):4914–4923CrossRefPubMed

43.

Thomsen K, Riis BJ, Johansen JS, Christiansen C, Rødbro P (1987) Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy. Gynecol Endocrinol 1(2):169–175CrossRefPubMed

44.

Banks E, Beral V, Reeves G, Balkwill A, Barnes I (2004) Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women. JAMA 291(18):2212–2220CrossRefPubMed

45.

Karim R, Dell RM, Greene DF, Mack WJ, Gallagher JC, Hodis HN (2011) Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization. Menopause 18(11):1172–1177CrossRefPubMedPubMedCentral

46.

Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, Chlebowski RT, Gass M, LaCroix A, Manson JE, Prentice RL, Rossouw J, Stefanick ML, WHI Investigators (2008) Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 299(9):1036–1045CrossRefPubMed

47.

LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, Margolis KL, Stefanick ML, Brzyski R, Curb JD, Howard BV, Lewis CE, Wactawski-Wende J, Investigators WHI (2011) Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 305(13):1305–1314CrossRefPubMedPubMedCentral

48.

Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, Anderson G, Howard BV, Thomson CA, LaCroix AZ, Wactawski-Wende J, Jackson RD, Limacher M, Margolis KL, Wassertheil-Smoller S, Beresford SA, Cauley JA, Eaton CB, Gass M, Hsia J, Johnson KC, Kooperberg C, Kuller LH, Lewis CE, Liu S, Martin LW, Ockene JK, O’Sullivan MJ, Powell LH, Simon MS, Van Horn L, Vitolins MZ, Wallace RB (2013) Menopausal hormone therapy and health outcomes during the intervention and extended post-stopping phases of the Women’s Health Initiative randomized trials. JAMA 310(13):1353–1368CrossRefPubMed

49.

Metz S, Klein C, Morton N (1987) Rebound hypertension after discontinuation of transdermal clonidine therapy. Am J Med 82(1):17–19CrossRefPubMed

50.

Diehl P, Halscheid C, Olivier C, Helbing T, Bode C, Moser M (2011) Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 100(9):765–771CrossRefPubMed

51.

McClung M, Clemmesen B, Daifotis A, Gilchrist NL, Eisman J, Weinstein RS, Fuleihan GEH, Reda C, Yates AJ, Ravn P, Alendronate Osteoporosis Prevention Study Group (1998) Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Ann Intern Med 128(4):253–261CrossRefPubMed

52.

Greenspan SL, Vujevich KT, Brufsky A, Lembersky BC, van Londen GJ, Jankowitz RC, Puhalla SL, Rastogi P, Perera S (2015) Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial. Osteoporos Int 26(6):1857–1864CrossRefPubMedPubMedCentral

53.

Wagner-Johnston ND, Sloan JA, Liu H, Kearns AE, Hines SL, Puttabasavaiah S, Dakhil SR, Lafky JM, Perez EA, Loprinzi CL (2015) 5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial. Cancer 121(15):2537–2543CrossRefPubMed

54.

Rittmaster RS, Bolognese M, Ettinger MP, Hanley DA, Hodsman AB, Kendler DL, Rosen CJ (2000) Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 85(6):2129–2134PubMed

55.

Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME (2003) Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Arch Intern Med 163(7):789–794CrossRefPubMed

56.

Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL, DAPS Investigators (2012) Final results of the DAPS (denosumab adherence preference satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23(1):317–326CrossRefPubMedPubMedCentral

57.

McClung M, Miller P, Recknor C, Mesenbrink P, Bucci-Rechtweg C, Benhamou CL (2009) Zoledronic acid for the prevention of bone loss in postmenopausal women with low bone mass: a randomized controlled trial. Obstet Gynecol 114(5):999–1007CrossRefPubMed

58.

Grey A, Bolland MJ, Horne A, Wattie D, House M, Gamble G, Reid IR (2012) Five years of anti-resorptive activity after a single dose of zoledronate—results from a randomized double-blind placebo-controlled trial. Bone 50(6):1389–1393CrossRefPubMed

Titel: Cancel the denosumab holiday
verfasst von: M. R. McClung
Publikationsdatum: 01.03.2016
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 5/2016
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-016-3553-3

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