Zoledronic Acid in Acute Spinal Cord Injury

Maintenance of bone mass following spinal cord injury (SCI) is essential to fracture
prevention and the associated morbidity of bed rest and further secondary complications.
Intravenous (IV) zoledronic acid (ZA) has been shown to be more effective than other agents
in reducing bone mass resorption and fracture of the legs in post-menopausal women, but has
not been studied in acute spinal cord injury. Two previous studies of ZA in persons with
subacute SCI, while promising, were inconclusive. As stated in the long range plan of the
National Institute on Disability and Rehabilitation Research (NIDRR), one goal in the area of
health and function is to "focus on the onset of new conditions…exacerbation of existing
conditions, or the development of coexisting conditions." This study is intended to
demonstrate reduction in loss of bone mass at the hip and knee regions in acute SCI in a
rigorous study of sufficient size to determine effectiveness of our intervention.

Inclusion Criteria:

- Ages 18-65, male or female

- Traumatic SCI with Neurological level C4-T10, AIS (ASIA Impairment Scale) A,

- Serum calcium level >7.0 mg/dL) at time of study drug administration

- Screening baseline serum 25OH (25-hydroxy) vitamin D of at least 13 ng/ml

- No medical contraindication to supplemental vitamin D for participants whose levels
are >13 ng/ml but sub-therapeutic (<32ng/ml)

- No medical contraindication to supplemental calcium

- Weight under 300 pounds, which is the maximum permitted on the DXA scanner

Exclusion Criteria:

- Ventilator-dependent individuals

- Chronic steroid use (defined as >6 months)

- Rheumatoid disease with use of prior disease modifying anti-rheumatic drugs (DMARDs)
affecting bone density

- History of osteoporosis or of treatment for osteopenia or osteoporosis with
bisphosphonates, or selective reuptake estrogen modifying agents

- Current use of medications* including bisphosphonates to treat osteoporosis (*note
that prior calcium or vitamin D use is not an exclusion criteria)

- History of more than one lower extremity osteoporosis-related fracture

- Chronic renal insufficiency, creatinine clearance < 35 ml/min, during screening

- End stage liver or kidney disease

- Medical conditions resulting in hypogonadal states that affect bone density

- Uncontrolled thyroid disease/thyrotoxicosis

- Hereditary or acquired metabolic bone disorder

- History of use of unfractionated heparin for >1 year

- History of selected antiseizure medications, specifically phenobarbital, phenytoin,
carbamazepine, sodium valproate >1 year

- Acute or chronic bilateral lower extremity fractures involving tibia or femur, with
placement of surgical hardware in any areas of above locations

- Severe hypotension requiring use of intravenous blood pressure agents such as
dopamine, norepinephrine or phenylephrine. Exception may allow for patients on
pressors who arm experiencing hypotension as they acclimate to upright posture.

- Inability to provide informed consent and understand the consent process

- Facial fractures requiring oral surgery

- Dental surgery or oral maxillofacial surgery within 2 weeks of anticipated study drug
administration

- Pregnancy present on admission

- Vitamin D deficiency on admission testing (serum 25-OH D reported as < 13 ng/mL )

- Patients with an established reaction to, or history of, anaphylactic shock to aspirin