FES-Rowing Versus Zoledronic Acid to Improve Bone Health in Spinal Cord Injury (SCI)

This research study was designed to determine the effects of functional electrical
stimulation (FES) rowing and a drug called zoledronic acid in bone health in individuals who
have suffered a spinal cord injury (SCI). The investigators hoped to learn if zoledronic
acid treatment would increase bone mineral density in persons with chronic spinal cord
injury. This was designed and conducted as a three center study with multiple investigators.
The investigators also had a goal to find out if zoledronic acid is safe for persons with
SCI without causing too many side effects.

The Prime recipient of funding is Spaulding Rehabilitation Hospital (SRH). Dr. Leslie Morse
is the Principal Investigator for the study, the coordination of the study was located at
Spaulding Rehabilitation Hospital. Through a sub-award a research group from the Veterans
Administration of Boston Healthcare System was contracted to conduct DXA scans, blood draws
and zoledronic acid administration to support this study. Through another sub-award from
SRH, another Investigator from Massachusetts General Hospital (MGH) participated conducting
CT scans for the study. All adverse events related to this study were to be monitored and
recorded by investigators at SRH.

Seventy subjects age 18 years or older and wheelchair dependent at least 50% of the time
because of an SCI were enrolled. Enrollment and initial screening for the study and follow
up was performed at SRH. After enrollment the subjects were randomized to 1) FES-rowing
alone or 2) FES-rowing plus a 1-time infusion of zoledronic acid. Following a variable
period of strength training which was necessary for preparing quads and hamstrings for
extended FES use, enrolled participants were planned to begin a regular rowing program for
12 months at the Cardiovascular Laboratory at the Spaulding Rehabilitation Hospital . DXA
scans to measure bone mineral density were planned to be performed at the VA Boston
Healthcare System-Jamaica Plain Campus (VABHS) three times during the study on all
participants. In addition, 25 subjects in each arm of the study were planned to receive CT
scans of their knees at MGH at the beginning and end of the study. Up to 20 subjects were to
have an additional CT scan (at MGH) six months into rowing. Research blood samples were
planned to be collected at VABHS five times during duration of the study and stored at the
VA for further study of molecular markers of bone turnover. All participants were expected
to be screened for renal function and calcium and vitamin D levels at the beginning and end
of the study, with additional renal screening done before and after the zoledronic acid
infusion. Calcium and vitamin D supplements were to be provided to each subject throughout
the study. Those with insufficient vitamin D levels were to be provided additional repletion
and planned to be periodically rechecked. Up to 15 male subjects were asked to have two
echocardiograms at one of the SRH sites - one at the beginning of the study and the other
halfway through the year-long rowing regimen.

Inclusion Criteria:

- male and female SCI outpatients

- women of child bearing age will be required to use an acceptable birth control method
throughout the study

- aged 18 - over the age of 40

- physician's cardiac clearance to exercise

- who were at least age 14 at time of injury

- who are at least 18 months post injury

- who have a C4 spinal cord injury or lower

Exclusion Criteria:

- initial blood pressure higher than 140/90

- patients with orthostatic hypotension

- an active grade 2 or greater pressure ulcers

- lower extremity contractures

- history of significant arrhythmias

- coronary disease

- diabetes

- neurological or renal disease

- cancer

- other neurological disease (i.e. stroke, peripheral neuropathy, myopathy)

- any implanted electronic device

- active treatment for epilepsy

- recent weight change

- regular use of tobacco

- family history of arrhythmia or sudden cardiac death

- current use of cardioactive or antidepressant medications

- current use of medications that may affect fracture risk including:

- bisphosphonates

- PTH and PTH analogs

- androgenic steroids

- estrogenic steroids

- glucocorticoids

- antiepileptics

- lithium.

- Any subject with a planned invasive dental procedure will be excluded.

These criteria will be reviewed by telephone survey followed by a health exam where blood
pressure will be assessed and a skin and neurological exam performed.