Denosumab Administration After 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
acute SCI. Setting: patient enrollment, study drug administration and DXA scanning will be
completed at the Kessler Institute for Rehabilitation (KIR) and pQCT measurements will be
performed at Columbia University. A Randomized, double-blind, placebo-controlled parallel
group trial.

Twenty-four subjects with acute, motor complete SCI (≤12 weeks) who have been admitted to the
Kessler Institute for Rehabilitation (KIR) will be recruited for participation. The age of
study participation will be males between the ages of 18 and 65 years old and females between
the ages of 18 and 50 years old. Primary outcome measure will be BMD as measured by DXA and
microarchitecture as measured by pQCT at the hip and knee.

Inclusion Criteria:

1. Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A
and B];

2. Duration of injury <12 weeks; 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. Heterotopic ossification of the knee region (HO limited to the hip region only will
not exclude subject participation);

11. History of chronic alcohol abuse;

12. Diagnosis of Hypocalcemia;

13. Pregnancy;

14. Existing dental condition/dental infection

15. Any patient taking a bisphosphonate for heterotopic ossification (HO);

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

17. 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.