Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation

Postmenopausal Osteoporosis Clinical Trial

— AfterDmab  

Official title:

The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02499237
• Other study ID #: AfterDmab
• Status: Completed
• Phase: Phase 4
• Start date: July 2015
• Est. completion date: November 26, 2018

Study information

• Verified date: March 2019
• Source: 424 General Military Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: November 26, 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Drug:
• Denosumab
Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year
• Zoledronic acid
Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year

Locations

Country	Name	City	State
Greece	251 Airforce & VA General Hospital	Athens
Greece	424 General Military Hospital	Thessaloniki

Sponsors (3)

Lead Sponsor	Collaborator
424 General Military Hospital	251 Hellenic Air Force & VA General Hospital, Leiden University Medical Center

Country where clinical trial is conducted

Greece, 

References & Publications (4)

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. — View 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. — View Citation

Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J; Amg Bone Loss Study Group. 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):222-9. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bone mineral density of the lumbar spine	differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry	from 12 to 24 months
Secondary	bone mineral density of the femoral neck	differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry	from 12 to 24 months
Secondary	C-terminal telopeptide of type I collagen	differences between the 2 arms in the changes of C-terminal telopeptide of type I collagen	from 12 to 15, 18, 24 months
Secondary	propeptide of procollagen type I	differences between the 2 arms in the changes of propeptide of procollagen type I	from 12 to 15, 18, 24 months
Secondary	bone mineral density of the lumbar spine	differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry	from baseline to 12 months
Secondary	bone mineral density of the femoral neck	differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry	from baseline to 12 months