Comparative Antiresorptive Efficacy Discontinuation of Denosumab

Phase 4

Active, not recruiting

• Conditions: Osteoporosis; Osteoporosis, Postmenopausal
• Interventions: Drug: denosumab; Drug: raloxifene; Drug: alendronate

• Registration Number: NCT03623633
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-08-06
• Study First Posted: 2018-08-09
• Study Start: 2018-11-30
• Primary Completion: 2023-02-01
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-05
• Last Update Posted: 2023-06-07
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 51

Inclusion Criteria

• women aged 45+
• postmenopausal
• osteoporotic with high risk of fracture as per National Osteoporosis Foundation guidelines

Exclusion Criteria

• no significant previous use of bone health modifying treatments
• hip fracture within one year of enrollment
• known congenital or acquired bone disease other than osteoporosis
• significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease
• abnormal calcium or parathyroid hormone level
• serum vitamin D <20 ng/dL
• anemia (hematocrit <32%)
• history of malignancy (except non-melanoma skin carcinoma)
• excessive alcohol use or substance abuse
• extensive dental work involving extraction or dental implant within the past 6 months or in the upcoming 12 months
• known contraindications to denosumab, alendronate, or raloxifene

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab and Raloxifene	denosumab	denosumab and raloxifene
Denosumab and Raloxifene	raloxifene	denosumab and raloxifene
Denosumab and Alendronate	alendronate	denosumab and alendronate
Denosumab and Alendronate	denosumab	denosumab and alendronate

Primary Outcome Measures

Name	Time	Method
Serum c-telopeptide (CTX)	Month 12 to 18 months	Change in serum CTX between month 12 and month 18
Bone mineral density (BMD)	Month 24 to 36 months	Change in PA spine BMD between month 24 and month 36

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States