We read with great interest the EMAS position paper by Anagnostis et al., regarding
drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis [
[1]
]. We would like to make two points:
- Anagnostis P.
- Paschou S.A.
- Mintziori G.
- Ceausu I.
- Depypere H.
- Lambrinoudaki I.
- Mueck A.
- Pérez-López F.R.
- Rees M.
- Senturk L.M.
- Simoncini T.
- Stevenson J.C.
- Stute P.
- Trémollieres F.A.
- Goulis D.G.
Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS
position statement.
Maturitas. 2017; https://doi.org/10.1016/j.maturitas.2017.04.008
- 1.Since the efficacy of continuing alendronate beyond 5 and up to 10 years or zoledronate beyond 3 and up to 6–9 years is evaluated in terms of fractures, readers should keep in mind that the studies referenced did not have an adequate number of patients to prove anti-fracture efficacy, especially when it comes to non-vertebral or hip fractures.
- 2.Regarding denosumab discontinuation and the risk of fractures, first a target hip BMD T-score of −1.5 should be considered before stopping treatment [[2]], and second there should be a distinction between treatment-naïve patients and prior bisphosphonate users [
- Ferrari S.
- Libanati C.
- Adami S.
- Brown J.P.
- Cosman F.
- Czerwiński E.
- de Gregório L.H.
- Malouf J.
- Reginster J.-Y.
- Daizadeh N.S.
- Wang A.
- Wagman R.B.
- Lewiecki E.M.
Relationship between total hip BMD T-score and incidence of nonvertebral fracture with up to 8 years of denosumab treatment.J. Bone Miner. Res. 2015; 30 (Available at https://www.asbmr.org/education/AbstractDetail?aid=11d861c9-68e4-4994-88e0-c6b94948e898. (accessed 18 April 2017))[3]]. It is clear that for the former set of patients, fractures are attributed to excess osteoclast activity following denosumab discontinuation [- Anastasilakis A.D.
- Polyzos S.A.
- Makras P.
- Aubry-Rozier B.
- Kaouri S.
- Lamy O.
Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases.J. Bone Miner. Res. 2017; https://doi.org/10.1002/jbmr.3110[4]], are clinical, so far exclusively vertebral, and in most cases multiple [[3]]. Furthermore, a new post-hoc analysis of FREEDOM data reported a greater percentage of multiple vertebral fractures in the denosumab group than in the control group (60.7% vs 34.5%) [- Anastasilakis A.D.
- Polyzos S.A.
- Makras P.
- Aubry-Rozier B.
- Kaouri S.
- Lamy O.
Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases.J. Bone Miner. Res. 2017; https://doi.org/10.1002/jbmr.3110[5]]. Given that denosumab discontinuation is accompanied by a rapid dramatic increase in bone turnover above pre-treatment levels, a decrease in BMD to baseline values within the first year off-treatment, and a subset of these patients are at risk for multiple vertebral fractures, discontinuation should be carefully considered irrespective of BMD values until further knowledge is gained.- Brown J.P.
- Ferrari S.
- Gilchrist N.
- Beck Jensen J.E.
- Pannacciulli N.
- Recknor C.
- Roux C.
- Smith S.
- Torring O.
- Valter I.
- Wagman R.B.
- Wang A.T.
- Cummings S.R.
Discontinuation of denosumab and associated fracture incidence: analysis from FREEDOM and its extension.J. Bone Miner. Res. 2016; 31 (Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=51d4e88b-f79d-47e2-a15b-134f0c57b52e. (accessed 18 April 2017))
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References
- Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statement.Maturitas. 2017; https://doi.org/10.1016/j.maturitas.2017.04.008
- Relationship between total hip BMD T-score and incidence of nonvertebral fracture with up to 8 years of denosumab treatment.J. Bone Miner. Res. 2015; 30 (Available at https://www.asbmr.org/education/AbstractDetail?aid=11d861c9-68e4-4994-88e0-c6b94948e898. (accessed 18 April 2017))
- Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases.J. Bone Miner. Res. 2017; https://doi.org/10.1002/jbmr.3110
- Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment.Eur. J. Endocrinol. 2017; 176: 677-683
- Discontinuation of denosumab and associated fracture incidence: analysis from FREEDOM and its extension.J. Bone Miner. Res. 2016; 31 (Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=51d4e88b-f79d-47e2-a15b-134f0c57b52e. (accessed 18 April 2017))
Article info
Publication history
Published online: April 26, 2017
Received:
April 18,
2017
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© 2017 Elsevier B.V. All rights reserved.
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- Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statementMaturitasVol. 101
- PreviewBisphosphonates are structural analogues of inorganic pyrophosphate, where the oxygen atom has been substituted by a carbon atom. Differences in the R2 side-chain bound to the carbon atom and the nitrogen group determine their variations in duration of action, bone affinity and anti-fracture efficacy [1,2]. Bisphosphonates inhibit enzymes involved in osteoclastic activity, and thus suppress bone resorption [1,2]. The main bisphosphonates are alendronate, risedronate, ibandronate and zoledronic acid, which constitute the first-line therapeutic agents in both postmenopausal and male osteoporosis, as they have well-documented anti-fracture efficacy [1,2].
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- Bisphosphonates or denosumab discontinuation and risk of fractures: Response to the Letter by Anastasilakis et al.MaturitasVol. 102
