Abstract
Introduction
Case reports of women sustaining multiple vertebral fractures (VF) soon afterdenosumab discontinuation are accumulating.
Methods
We report a woman with five new vertebral fractures in ~8 months following discontinuation of long-term odanacatib (ODN), an experimental cathepsin K inhibitor.
Results
DXA examination demonstrated an ~12% decline in bone mineral density (BMD) and ~9% decline in trabecular bone score (TBS) since ODN discontinuation. Laboratory evaluation did not reveal a secondary cause of bone loss.
Conclusions
This case mimics observations following denosumab discontinuation, but, to our knowledge, is the first reported with ODN and the first documenting substantial decline in TBS. While not directly clinically relevant as ODN is no longer being developed, this case raises the possibility that a syndrome of multiple vertebral fractures could follow discontinuation of various potent osteoporosis therapies that produce major BMD increases but do not have persisting bone effects (i.e., all non-bisphosphonates). Use of antiresorptive therapies to prevent rapid bone loss following discontinuation of potent bone active agents seems appropriate. Identification of those patients who could be at risk for the multiple VF syndrome is needed.
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References
Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B (2017) Severe rebound-associated vertebral fractures after denosumab discontinuation: 9 clinical cases report. J Clin Endocrinol Metab 102:354–358
Popp AW, Zysset PK, Lippuner K (2016) Rebound-associated vertebral fractures after discontinuation of denosumab—from clinic and biomechanics. Osteoporos Int 27:1917–1921
Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O (2017) Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res 32:1291–1296
Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O (2016) Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int 27:1923–1925
Polyzos SA, Terpos E (2016) Clinical vertebral fractures following denosumab discontinuation. Endocrine 54:271–272
Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JEB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP (2017) Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. https://doi.org/10.1002/jbmr.3337
Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J (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 43:222–229
Miller PD, Wagman RB, Peacock M, Lewiecki EM, Bolognese MA, Weinstein RL, Ding B, San Martin J, McClung MR (2011) Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial. J Clin Endocrinol Metab 96:394–402
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 96:972–980
Frost HM (2003) Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275:1081–1101
Ma S, Goh EL, Jin A, Bhattacharya R, Boughton OR, Patel B, Karunaratne A, Vo NT, Atwood R, Cobb JP, Hansen U, Abel RL (2017) Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci Rep 7:43399
Bone HG, Dempster DW, Eisman JA, Greenspan SL, McClung MR, Nakamura T, Papapoulos S, Shih WJ, Rybak-Feiglin A, Santora AC, Verbruggen N, Leung AT, Lombardi A (2015) Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos Int 26:699–712
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 27:2251–2258
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 26:242–251
Rao SD, Qiu S, Dhaliwal R, Bhadada SK (2017) Letter to the editor: severe rebound-associated vertebral fractures after denosumab discontinuation. J Clin Endocrinol Metab 102:2111
Silva BC, Broy SB, Boutroy S, Schousboe JT, Shepherd JA, Leslie WD (2015) Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 2: trabecular bone score. J Clin Densitom 18:309–330
Muschitz C, Kocijan R, Haschka J, Pahr D, Kaider A, Pietschmann P, Hans D, Muschitz GK, Fahrleitner-Pammer A, Resch H (2015) TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures. Bone 79:259–266
van der Zwaard BC, van Hout W, Hugtenburg JG, van der Horst HE, Elders PJ (2017) Adherence and persistence of patients using oral bone sparing drugs in primary care. Fam Pract 34:525–531
Fahrleitner-Pammer A, Papaioannou N, Gielen E, Feudjo Tepie M, Toffis C, Frieling I, Geusens P, Makras P, Boschitsch E, Callens J, Anastasilakis AD, Niedhart C, Resch H, Kalouche-Khalil L, Hadji P (2017) Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium. Arch Osteoporos 12:58
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Binkley, N., Krueger, D. & de Papp, A.E. Multiple vertebral fractures following osteoporosis treatment discontinuation: a case-report after long-term Odanacatib. Osteoporos Int 29, 999–1002 (2018). https://doi.org/10.1007/s00198-018-4385-0
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DOI: https://doi.org/10.1007/s00198-018-4385-0