Effects of Denosumab on Bone Fusion in Osteoporotic Patients After Lumbar Fusion

Study Overview
=================
Brief Summary
-----------------
Lumbar fusion is an accepted and effective technique for the treatment of lumbar degenerative disease. As the population ages, disability associated with spinal pathology and spinal surgery is rapidly increasing and there is a concomitant increase in prevalence of osteoporosis which is a detrimental factor for Lumbar fusion and instrumentation. Osteoporosis-related bone fragility is a primary reason for spinal fusion failure, implant fixation failure, and vertebral compression fractures above or below the fusion sites. Denosumab is a human monoclonal antibody against RANKL, it inhibits osteoclast mediated bone destruction and has been found to be effective in treating osteoporosis, including reducing bone turnover markers, increasing bone mineral density (BMD), and reducing fractures. But few studies focus on the effects of Denosumab on lumbar fusion. In this study, we include osteoporotic patients with lumbar degenerative disease who have had lumbar interbody fusion surgery. The patients were randomized to either treatment of Denosumab or no treatment. All these patients are followed at 3, 6, 9, 12 months postoperation. During these periods, we detect bone metabolism and bone fusion of these patients. Finally, we would report whether Denosumab can improve bone metabolism and promote bone fusion or not.

Official Title
-----------------
The Effects of Denosumab on Bone Fusion and Bone Metabolism in Osteoporotic Patients With Lumbar Degenerative Disease After Lumbar Interbody Fusion

Conditions
-----------------
Osteoporosis, Fusion of Spine, Lumbar Region

Intervention / Treatment
-----------------
* Drug: Denosumab 60 mg/ml Injectable Solution [Prolia]
* Drug: calcium and vitamin D


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of degenerative lumbar diseases with symptoms of low-back pain and/or leg pain for at least 3 months, which was not be adequately controlled by nonoperative treatments. Diagnosis of osteoporosis, defined as a bone mineral density (BMD) at lumbar or femoral neck with 2.5 standard deviations or more below the mean peak bone mass (T scores <-2.5 SD) measured by dual-energy X-ray absorptiometry (DXA). Patients will be underwent single-level or two-level lumbar interbody fusion. Exclusion Criteria: Paget disease of bone, Low laboratory tests for calcium, Previous radiation treatment or fusion surgery to lumbar spine, Bone tumors, Bone infection, Acute vertebral fractures Severe spinal deformities such as degenerative scoliosis, Other metabolic bone disease, History of a anti-osteoporosis medication Combined with severe morbidities, Uncorrected bleeding diatheses Application of steroids.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Patients in this group are received denosumab (60 mg) subcutaneously at one week and 26 weeks after the lumbar fusion surgery, combined with receiving daily calcium (≥1·0 g) and vitamin D (≥400 IU). | Drug: Denosumab 60 mg/ml Injectable Solution [Prolia]<br>* Denosumab, 60mg(1ml), subcutaneously, totally two times, with one time at 1-week postoperatively and another time at 26-week postoperatively.<br>Drug: calcium and vitamin D<br>* calcium (≥1·0 g) and vitamin D (≥400 IU).<br>|
| Sham Comparator: Control group<br>Patients in this group are only received daily calcium (≥1·0 g) and vitamin D (≥400 IU) after the lumbar fusion surgery. | Drug: calcium and vitamin D<br>* calcium (≥1·0 g) and vitamin D (≥400 IU).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lumbar fusion rate | Fusion rate assessed by CT scan and dynamic radiograph | 3-month post-operation | 
| lumbar fusion rate | Fusion rate assessed by CT scan and dynamic radiograph | 6-month post-operation | 
| lumbar fusion rate | Fusion rate assessed by CT scan and dynamic radiograph | 9-month post-operation | 
| lumbar fusion rate | Fusion rate assessed by CT scan and dynamic radiograph | 12-month post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN) | To assess bone metabolism, serum samples will be collected under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively. | pre-operation | 
| Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN) | To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively. | 3-month post-operation | 
| Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN) | To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively. | 6-month post-operation | 
| Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN) | To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively. | 9-month post-operation | 
| Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN) | To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively. | 12-month post-operation |