The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

The primary objective of this study is to test the efficacy of a potent anti-resorptive
agent, denosumab [receptor activator of nuclear factor-κB ligand (RANKL) antibody; Amgen
Inc.] to preserve bone mass at the hip and knee and trabecular connectivity at the knee after
subacute motor-incomplete SCI [American Spinal Injury Association (AIS) neurological
classification scale C and D] at the James J. Peters VA Medical Center (JJPVAMC) and Kessler
Institute for Rehabilitation (KIR). A randomized, double-blind, placebo-controlled, parallel
group trial will be performed in thirty-two subjects with acute, motor-incomplete SCI (≤6
months) who have been admitted to JJPVAMC or the KIR. Denosumab (60 mg SC) will be
administered at baseline, 6, and 12 months; the placebo group will receive normal saline
subcutaneously. Denosumab will be administered as soon as possible, but up to 24 weeks, after
SCI. The last dose of denosumab and placebo will be administered at 6 months, with the
anticipated effect of the drug to persist and inhibit bone resorption at least until the 12
month time point.

Inclusion Criteria:

1. Motor incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) grades
C and D];

2. Duration of injury < 6-months; and

3. Males between the ages of 18 and 65 years old and females between the ages of 18 and
50 years old.

Exclusion Criteria:

1. Extensive life-threatening injuries in addition to SCI;

2. Acute fracture or extensive bone trauma;

3. History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)

4. Post-menopausal women;

5. Men with known hypogonadism prior to SCI;

6. Anabolic or Steroid hormonal therapy; within the past year and longer than six months;

7. Hyperthyroidism;

8. Cushing's disease or syndrome;

9. Severe underlying chronic disease;

10. History of chronic alcohol abuse;

11. Diagnosis of Hypocalcemia;

12. Pregnancy;

13. Existing dental condition/dental infection;

14. Diagnosis of heterotopic ossification at the hip and/or knee region and receiving a
bisphosphonates [e.g. alendronate sodium (Fosamax) or etidronate disodium (Didronel)]
that will no longer make participants eligible to receive the study medication/placebo
but are still eligible to complete follow-up outcome measures as described in the work
schedule;

15. Current diagnosis of cancer or history of cancer; and

16. Any patient receiving moderate or high dose corticosteroids (>40 mg/d prednisone or an
equivalent dose of other corticosteroid) for longer than one week, not including drug
administered in an attempt to preserve neurological function at the time of acute SCI.