Variability of Denosumab Densitometric Response in Postmenopausal Osteoporosis

Overview

Journal Rheumatol Int

Specialty Rheumatology

Date 2018 Jan 25

PMID 29362876

Citations 2

Authors

M Laroche

C Baradat

A Ruyssen-Witrand

Y Degboe

Affiliations

Soon will be listed here.

Abstract

The objective of our prospective study is to specify the variability of densitometric response to Denosumab, given in the second line, and to try to understand the reasons. All menopausal patients with primary osteoporosis, treated by Denosumab in our centre from 2014 to 2015, were included in this open prospective work. At T0, the patient's age, type of fracture, and previous treatments were collated. At T0 and T1, after 1 year of treatment by Dmab, a DXA of the spine and the hip and a determination of CTX were performed. Sixty-three patients aged 68.8 ± 8.3 years were included. The median number of treatments prescribed for osteoporosis before switch to Denosumab was 2.4. The median duration of these treatments was 7.2 years. At T1, CTX was less than 33 pg/ml (minimum threshold for our assay kit) in all patients. The median BMD in the spine increased by + 5.44% compared to T0. 14 patients in the upper quartile had a median BMD gain in the spine of + 11.07%. Fourteen patients in the lower quartile had a median BMD gain in the spine of + 0.6%. Only the duration of previous treatments, which was greater in the non-responder group, differed between these two groups. In the total cohort, the spinal densitometric gain was negatively correlated with the age of the patient at baseline (p = 0.04), the duration of previous treatment (p = 0.02), and positively with the CTX level (p = 0.05). The Dmab densitometric response is highly variable, partly explained by the duration of previous treatments and the level of bone resorption at initiation of treatment.

Citing Articles

Risk factors for nonresponse to 2 years of denosumab administration in patients with osteoporosis: A retrospective single-center cohorts study.

Yamamoto A, Nagao M, Nishizaki Y, Maeda E, Ishijima M Health Sci Rep. 2024; 7(4):e1993.

PMID: 38585014 PMC: 10995440. DOI: 10.1002/hsr2.1993.

Denosumab mid-term densitometric gain in postmenopausal osteoporosis women in clinical practice: comment on "Variability of denosumab densitometric response in postmenopausal osteoporosis".

Torrente-Segarra V, Roig-Vilaseca D Rheumatol Int. 2018; 38(6):1161-1162.

PMID: 29546636 DOI: 10.1007/s00296-018-4007-3.

References

Eastell R, Boonen S, Cosman F, Reid I, Palermo L, Cummings S . Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study. J Bone Miner Res. 2014; 30(3):570-4. DOI: 10.1002/jbmr.2361. View

Miller P, Pannacciulli N, Brown J, Czerwinski E, Nedergaard B, Bolognese M . Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016; 101(8):3163-70. PMC: 4971333. DOI: 10.1210/jc.2016-1801. View

Brown J, Prince R, Deal C, Recker R, Kiel D, de Gregorio L . Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2008; 24(1):153-61. DOI: 10.1359/jbmr.0809010. View

Recknor C, Czerwinski E, Bone H, Bonnick S, Binkley N, Palacios S . Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol. 2013; 121(6):1291-1299. DOI: 10.1097/AOG.0b013e318291718c. View

Roux C, Hofbauer L, Ho P, Wark J, Zillikens M, Fahrleitner-Pammer A . Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone. 2013; 58:48-54. DOI: 10.1016/j.bone.2013.10.006. View

Kendler D, Roux C, Benhamou C, Brown J, Lillestol M, Siddhanti S . Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2009; 25(1):72-81. DOI: 10.1359/jbmr.090716. View

Ebina K, Hashimoto J, Kashii M, Hirao M, Kaneshiro S, Noguchi T . The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis. J Bone Miner Metab. 2016; 35(1):91-98. DOI: 10.1007/s00774-015-0731-x. View

Ravaud P, Reny J, Giraudeau B, Porcher R, Dougados M, Roux C . Individual smallest detectable difference in bone mineral density measurements. J Bone Miner Res. 1999; 14(8):1449-56. DOI: 10.1359/jbmr.1999.14.8.1449. View

Reid I, Miller P, Brown J, Kendler D, Fahrleitner-Pammer A, Valter I . Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010; 25(10):2256-65. DOI: 10.1002/jbmr.149. View

10.

Miller P, Wagman R, Peacock M, Lewiecki E, Bolognese M, Weinstein R . 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. 2010; 96(2):394-402. DOI: 10.1210/jc.2010-1805. View

11.

Sebba A . Significance of a decline in bone mineral density while receiving oral bisphosphonate treatment. Clin Ther. 2008; 30(3):443-52. DOI: 10.1016/j.clinthera.2008.03.008. View

12.

McClung M, Lewiecki E, Cohen S, Bolognese M, Woodson G, Moffett A . Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006; 354(8):821-31. DOI: 10.1056/NEJMoa044459. View

13.

McClung M, Lewiecki E, Geller M, Bolognese M, Peacock M, Weinstein R . Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 2012; 24(1):227-35. PMC: 3536967. DOI: 10.1007/s00198-012-2052-4. View

14.

Cummings S, San Martin J, McClung M, Siris E, Eastell R, Reid I . Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8):756-65. DOI: 10.1056/NEJMoa0809493. View

15.

Roux C, Garnero P, Thomas T, Sabatier J, Orcel P, Audran M . Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis. Joint Bone Spine. 2005; 72(1):26-31. DOI: 10.1016/j.jbspin.2004.07.003. View

16.

Lewiecki E, Miller P, McClung M, Cohen S, Bolognese M, Liu Y . Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007; 22(12):1832-41. DOI: 10.1359/jbmr.070809. View

17.

Burnett-Bowie S, Saag K, Sebba A, de Papp A, Chen E, Rosenberg E . Prediction of changes in bone mineral density in postmenopausal women treated with once-weekly bisphosphonates. J Clin Endocrinol Metab. 2009; 94(4):1097-103. PMC: 5393373. DOI: 10.1210/jc.2008-1122. View

18.

Austin M, Yang Y, Vittinghoff E, Adami S, Boonen S, Bauer D . Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res. 2011; 27(3):687-93. PMC: 3415619. DOI: 10.1002/jbmr.1472. View

19.

Ominsky M, Libanati C, Niu Q, Boyce R, Kostenuik P, Wagman R . Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab. J Bone Miner Res. 2015; 30(7):1280-9. DOI: 10.1002/jbmr.2480. View