What side effects are associated with this type of intervention?

Romosozumab, which increases bone formation by inhibiting sclerostin, can cause side effects such as joint pain, headache, and potential cardiovascular events. Denosumab, which decreases bone resorption by inhibiting RANKL, can lead to side effects including hypocalcemia, osteonecrosis of the jaw, infections, and atypical femoral fractures. Both drugs are used to manage bone density and prevent fractures, but they come with these potential risks.

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments specifically for spinal cord injury that utilize the mechanisms of action seen in Romosozumab and Denosumab. Romosozumab, which increases bone formation by inhibiting sclerostin, and Denosumab, which decreases bone resorption by inhibiting RANKL, are primarily approved for the treatment of osteoporosis. These drugs are being studied for their potential benefits in maintaining bone mass in conditions like subacute spinal cord injury, but their use in SCI is not yet established or approved.

What other types of research exist?

Promising alternatives to Romosozumab followed by Denosumab for SCI patients could include other osteoclast inhibitors like Zoledronic Acid, which has shown efficacy in reducing skeletal-related events and improving bone density. Additionally, newer agents like Teriparatide, a parathyroid hormone analog that stimulates bone formation, could be considered. Clinical trials and further research in SCI-specific populations would be necessary to confirm their efficacy and safety.

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Monoclonal Antibodies

Romosozumab vs Denosumab for Osteoporosis After Spinal Cord Injury

Phase 4

Waitlist Available

Led By Steven C Kirshblum, M.D.

Research Sponsored by James J. Peters Veterans Affairs Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Traumatic motor-complete or incomplete SCI C4-L2 (AIS grade A-C)

Males and females (premenopausal) between the ages of 18 and 55 years old

Must not have

Abnormalities of endocrine glands such as hyperthyroidism, Cushing's disease or syndrome, etc.

Current diagnosis of cancer or history of cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 24 months

Awards & highlights

Pivotal Trial

Drug Has Already Been Approved

No Placebo-Only Group

Summary

This trial is testing two ways to use medications that help keep bones strong in people with recent spinal cord injuries. One method uses a medication that helps build new bone for a period and then switches to another medication that prevents bone loss for another period. The other method uses only the medication that prevents bone loss for a longer period.

Who is the study for?

This trial is for men and premenopausal women aged 18-55 with a recent traumatic spinal cord injury (SCI) between C4-L2, who have not taken certain osteoporosis medications other than calcium and vitamin D. Participants must have a specific bone density level above the knee and cannot have conditions like chronic alcohol abuse, cancer history, severe chronic diseases, or be pregnant.

What is being tested?

The study tests if treating patients first with Romosozumab for 12 months followed by Denosumab for another year helps maintain bone mass at the knee better than just using Denosumab alone for two years in individuals with subacute SCI.

What are the potential side effects?

Romosozumab may cause muscle pain, headache, joint pain; it has potential risks of heart attack, stroke and cardiovascular death. Denosumab can lead to low blood calcium levels, skin rash or infection risk due to weakened immune system.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a spinal cord injury between C4 and L2, with some level of paralysis.

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I am between 18 and 55 years old and if female, not past menopause.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition affecting my hormone glands, like an overactive thyroid or Cushing's.

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I have been diagnosed with cancer or have a history of it.

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I had a major leg bone fracture in the last year.

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I have bone cancer.

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I have or had heart disease or a stroke.

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I have a history of bone disease like osteoporosis.

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I am a woman who has gone through menopause.

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I do not have severe chronic diseases like COPD, heart failure, or kidney failure.

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I had low testosterone levels before my spinal cord injury.

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I have been on more than 40 mg/day of corticosteroids for over a week, not for acute spinal cord injury.

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I have high levels of calcium in my blood.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Bone mineral density (BMD) of the distal femur metaphysis

Side effects data

From 2016 Phase 3 trial • 245 Patients • NCT02186171

21%

Nasopharyngitis

Back pain

Hypertension

Constipation

Arthralgia

Headache

Procedural pain

Muscle spasms

Myalgia

Depression

Appendicitis perforated

Pneumonia

Implant site haematoma

Thoracic vertebral fracture

Death

Cerebral ischaemia

Depressed mood

Atrial flutter

Appendicitis

Osteoarthritis

Vascular encephalopathy

Urinary tract infection

Carotid artery stenosis

Anaemia postoperative

Haemorrhagic stroke

Cholecystitis

Non-cardiac chest pain

Benign prostatic hyperplasia

Angina unstable

Cardio-respiratory arrest

Basal cell carcinoma

Coronary artery stenosis

Wolff-Parkinson-White syndrome

Cerebrovascular accident

Escherichia sepsis

Subdural haematoma

Oropharyngeal cancer

Device related infection

Myocardial ischaemia

Gastrooesophageal reflux disease

Carotid arteriosclerosis

Cardiac failure

Laceration

Rib fracture

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Romosozumab 210 mg

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Romosozumab Baseline to Month 11 followed by Denosumab Month 12 to Month 24Experimental Treatment2 Interventions

Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive romosozumab (210mg SQ) once a month for 12 months. After 12 months the same twenty (20) individuals will receive denosumab (60mg SQ) at month 12 and 18.

Group II: Denosumab Baseline to Month 24Active Control1 Intervention

Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive denosumab (60 mg SQ) at baseline and 6, 12, and 18 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Denosumab

2013

Completed Phase 4

~12010

Romosozumab

2021

Completed Phase 4

~13930

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Romosozumab and Denosumab are two treatments being studied for their potential benefits in Spinal Cord Injury (SCI) patients. Romosozumab increases bone formation by inhibiting sclerostin, a protein that suppresses bone growth. Denosumab decreases bone resorption by inhibiting RANKL, a protein crucial for osteoclast activity, which breaks down bone tissue. These mechanisms are particularly important for SCI patients, who are prone to significant bone loss and fractures due to immobility. By promoting bone growth and reducing bone breakdown, these treatments aim to maintain bone density and reduce fracture risk, thereby improving the quality of life and clinical outcomes for SCI patients.