NCT03623633

Comparative Antiresorptive Efficacy Discontinuation of Denosumab

Active, enrolled Phase 4 Last updated 7 June 2023

What this trial tests

Phase 4 trial testing denosumab in Osteoporosis, Postmenopausal in 51 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

30 November 2018

Primary endpoint
1 February 2023

1 August 2023

Quick facts

Lead sponsor	Massachusetts General Hospital
Phase	Phase 4
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	51
Start date	30 November 2018
Primary completion	1 February 2023
Estimated completion	1 August 2023
Sites	1 location across United States

Drugs / interventions tested

• denosumab (DENOSUMAB) — full drug profile →
• alendronate — full drug profile →
• raloxifene (RALOXIFENE) — full drug profile →

Conditions studied

• Osteoporosis, Postmenopausal — all drugs for Osteoporosis, Postmenopausal →
• Osteoporosis — all drugs for Osteoporosis →

Sponsor

Massachusetts General Hospital

Who can join

45 and older, female only, with Osteoporosis, Postmenopausal or Osteoporosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Osteoporosis remains a significant healthcare burden for the United States. Current FDA-approved osteoporosis treatments include teriparatide, abaloparatide, bisphosphonates, denosumab, and raloxifene.

Denosumab is a fully human monoclonal antibody that specifically binds to receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab potently suppresses osteoclastic activity but bone turnover rapidly normalizes and bone turnover marker levels can rebound above baseline levels after the drug is discontinued.

This study will help us determine the optimal duration and relative efficacy of two oral antiresorptive medications that are FDA-approved for treatment of postmenopausal osteoporosis (alendronate and raloxifene) in preventing the rebound increase in bone turnover that occurs after denosumab discontinuation.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review.
   Kendler DL, Cosman F, Stad RK, Ferrari S. · · 2022 · cited 140× · PMID 34762286 · DOI 10.1007/s12325-021-01936-y
2. Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review.
   Anastasilakis AD, Makras P, Yavropoulou MP, Tabacco G, et al · · 2021 · cited 125× · PMID 33406802 · DOI 10.3390/jcm10010152
3. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
   Wells GA, Hsieh SC, Peterson J, Zheng C, et al · · 2025 · cited 6× · PMID 39868546 · DOI 10.1002/14651858.cd001155.pub3
4. One versus 2 years of alendronate following denosumab: the CARD extension.
   Tsai JN, Jordan M, Lee H, Leder BZ. · · 2024 · cited 3× · PMID 39112628 · DOI 10.1007/s00198-024-07213-2
5. The comparative efficacy of 12-mo of alendronate and raloxifene in maintaining denosumab-induced improvement in peripheral volumetric BMD, microarchitecture, and estimated strength.
   Leder BZ, Tsai JN, Ramchand SK, Jordan M, et al · · 2025 · PMID 41143157 · DOI 10.1093/jbmrpl/ziaf156