Clinical trial NCT02499237: Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation
Official title: The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postmenopausal Osteoporosis
Keywords: osteoporosis
denosumab
zoledronic acid
bone mineral density
bone markers
Lead sponsor: 424 General Military Hospital
Sponsor class: OTHER
Collaborators: name: 251 Hellenic Air Force & VA General Hospital
name: Leiden University Medical Center
First posted: 2015-07-16
Enrollment: 57
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In contrast with bisphosphonates,discontinuation of denosumab results in gradual loss of bone mineral density gains. The investigators aim to evaluate whether in patients treated with denosumab, a single zoledronic acid infusion would prevent the anticipated bone loss.

Detailed description: Discontinuation of denosumab results in a rebound rise of bone turnover markers and gradual loss of the achieved bone mineral density gains. In contrast, bisphosphonates, such as zoledronic acid, remain within the skeleton acting for several months or even years after discontinuation while maintaining bone mineral density despite the cessation of treatment. In this study, the investigators aim to evaluate changes in bone mineral density of the lumbar spine and the femoral neck, as well as in bone turnover markers one year after treatment discontinuation both in denosumab-treated women and in denosumab-treated women who switched to zoledronic acid infusion one year before treatment discontinuation.

Eligibility criteria: Inclusion Criteria:

* postmenopausal women
* osteopenic (T-score \> -2.5 but \< -1.0) after treatment with denosumab

Exclusion Criteria:

* secondary osteoporosis;
* diseases that could affect bone metabolism;
* medications that could affect bone metabolism;
* history of any antiosteoporotic treatment other than denosumab prior to randomization
* severe liver or kidney disease (creatinine clearance \< 60ml/min/1.73m2)

Primary outcomes:
measure: bone mineral density of the lumbar spine
timeFrame: from 12 to 24 months
Secondary outcomes:
measure: bone mineral density of the femoral neck
timeFrame: from 12 to 24 months
measure: C-terminal telopeptide of type I collagen
timeFrame: from 12 to 15, 18, 24 months
measure: propeptide of procollagen type I
timeFrame: from 12 to 15, 18, 24 months
measure: bone mineral density of the lumbar spine
timeFrame: from baseline to 12 months
measure: bone mineral density of the femoral neck
timeFrame: from baseline to 12 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 251 Airforce & VA General Hospital
city: Thessaloniki
country: Greece
facility: 424 General Military Hospital
Study officials:
affiliation: 424 General Military Hospital, Thessaloniki, Greece
name: Athanasios D Anastasilakis, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: 251 Airforce and VA General Hospital
name: Polyzois Makras, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. 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. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.
citation: Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC. 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. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.
citation: Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? N Engl J Med. 2012 May 31;366(22):2051-3. doi: 10.1056/NEJMp1202623. Epub 2012 May 9. No abstract available.
citation: Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis--where do we go from here? N Engl J Med. 2012 May 31;366(22):2048-51. doi: 10.1056/NEJMp1202619. Epub 2012 May 9. No abstract available.
citation: Anastasilakis AD, Polyzos SA, Yavropoulou MP, Appelman-Dijkstra NM, Ntenti C, Mandanas S, Papatheodorou A, Makras P. Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation. Calcif Tissue Int. 2021 May;108(5):587-594. doi: 10.1007/s00223-020-00785-1. Epub 2021 Jan 2.