Conditions: Diabetes Mellitus, Type 2 Osteoporosis
Keywords: Prolia Denosumab Diabetes
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 8
Healthy volunteers: no

Brief summary:
The goal of the study is to characterize the effect of Prolia® (denosumab) on indices of bone strength in type 2 diabetes (T2D). The investigational plan involves administration of Prolia® or identical placebo for 12 months as a randomized double-blind placebo-controlled trial in 66 T2D postmenopausal women assigned to Prolia® or placebo. The study will include assessment of different measures of bone quality: skeletal microarchitecture, including measurement of skeletal cortical pores; bone mineral density; bone material quality, and accumulation of advanced glycation endproducts (AGEs) in collagen. This information will help to determine whether Prolia® treatment in type 2 diabetes has skeletal benefits.

Detailed description:
Type 2 Diabetes Mellitus (T2DM) has become one of the most important diseases of our time. Recent research shows that diabetes has negative effects on bones and that people with diabetes might be more likely to break a bone. We don't know the reasons for this, but we suspect that normal bone replacement is slowed down in diabetes and this could slow down the growth of new bone. It is possible that the normal bone material becomes weaker because sugar-related components ("Advanced Glycation Endproducts") are making the bone more brittle. The investigators have shown in past research that people who have type 2 diabetes are more likely to have both weaker bone with lower "bone material strength" and also higher levels of sugar-related components ("Advanced Glycation Endproducts"). This study will focus on attempting to lower the sugar-related components ("Advanced Glycation Endproducts") by treating a group of patients with type 2 diabetes with a medication Prolia® or denosumab for one year. The investigators will compare postmenopausal women both before and after denosumab use and study them in terms of different bone features based on blood tests, bone imaging, a bone indentation test and a measurement of sugar-related components in the skin. This study will help to clarify if using this medication helps improve bone strength in women with diabetes.

Arms:
arm 1: Denosumab 60 mg/ml \[Prolia\] SC at baseline and 6 months. arm 2: Placebo SC at Baseline and 6 months.

Interventions: intervention 1: Denosumab 60 mg/ml [Prolia] intervention 2: Placebo
Intervention descriptions: intervention 1: Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits intervention 2: Placebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits

Protocol document:
Prot_SAP_001.pdf: 
Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab 
NCT03457818 
IRB Approval Date: June 24, 2020


Given the established deficits in type 2 diabetes (T2D) in microstructure and bone material properties, 
denosumab (DMAb) is an attractive therapeutic agent in the skeletal disease of T2D. In postmenopausal 
women without T2D, DMAb decreases bone resorption and reduces cortical porosity at the extremities 
and at the hip. Yet clinical evidence is lacking for the anti-osteoporotic efficacy of DMAb in T2D 
patients. The hypothesis of this study was that DMAb will improve indices of bone strength in T2D.   To 
determine whether DMAb treatment in T2D improves bone quality, this study was initiated.   
The study was a 12 month randomized (2:1 assignment) double-blind placebo controlled trial of T2D 
postmenopausal women assigned to either DMAb 60 mg SC at baseline and 6 months (n=44) or placebo 
(n=22); total study n=66. The statistical analysis plan was as follows:  the primary outcome was the 1-
year change in cortical porosity and the primary intent-to-treat analysis was a one-way ANCOVA with 
fixed effect of treatment (treated vs. placebo).  The study assessments consisted of a Screening Visit, a 
Baseline Visit, and 3, 6 and 12 Month Visits. Screening occurred within 31 days of the Baseline Visit.  
Subjects who met the inclusion/exclusion criteria as specified in the protocol were randomized at the 
Baseline Visit. All participants were given calcium 800 mg/d and vitamin D 1000 IU/day as needed to 
achieve a total calcium daily intake (from diet and supplements) of at least 1200 mg/d. 
The study was terminated by Amgen Inc. on June 10, 2020 because of insufficient patient 
recruitment that was exacerbated by the COVID pandemic.  Eight subjects had been enrolled.  After 
unblinding, the subjects who received active drug (n=4) were transitioned to alendronate within 7 months 
after the last study drug injection.