CompletedNCT02325414Updated Dec 2, 2025Results posted

Prevention of Bone Loss After Acute SCI by Zoledronic Acid

A Phase 2 interventional study of Zoledronic acid and Placebo in Spinal Cord Injury, Acute Spinal Cord Injury and Bone Loss, sponsored by Northwestern University. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-02.

Sponsored by Northwestern University · Phase 2, Interventional, and Prevention

Phase: Phase 2
Study type: Interventional
Enrollment: 60
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The overall objective of this study is to define an effective therapeutic approach, using currently available medication, to prevent or mitigate the loss of bone mass and bone strength that occurs after acute spinal cord injury.

Read the detailed description

This is a randomized, double-blind placebo-controlled study of zoledronic acid to evaluate its efficacy and safety over a 2 year period for the prevention of bone loss and maintenance of bone strength in individuals with recent onset SCI (see diagram below). Subjects will be randomized at the baseline visit to receive either zoledronic acid or placebo. At the end of the first year of the study, each treatment group will be re-randomized to either zoledronic acid or placebo to evaluate the durability of response to zoledronic acid and the utility of serum bone markers to guide therapeutic decision making. DXA imaging, CT imaging and bone markers will be obtained at baseline, 3 months, 6 months, 12 months, 18 months and 24 months.

Conditions studied

Spinal Cord Injury
Acute Spinal Cord Injury
Bone Loss
Osteoporosis

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Keywords

Osteoporosis
Spinal Cord Injury
Bone Diseases
Metabolic Bone Diseases
Musculoskeletal Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Nervous System
Wounds and Injuries
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Department of Defense

In context

Spinal Cord Injuries

1,948 studies on the registry are indexed under Spinal Cord Injuries; 505 are open to participants now.

This study's enrollment of 60 is above the median of 24 across 1,566 interventional studies indexed under Spinal Cord Injuries.

Browse Spinal Cord Injuries studies →

Lead sponsor

Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

In-patient at Rehabilitation Institute of Chicago (RIC) or an outpatient who was recently discharged from RIC
Males and females
Age >/=18 years
Medically stable in the opinion of subject's physiatrist
SCI at within 120 days inclusive at time of screening
SCI with inability to ambulate independently
ASIA Impairment Scale (AIS) A, B, or C, at time of study entry
Capable of positioning to have DXA performed
Able to tolerate acetaminophen
No known endocrinopathies (diabetes type 1 or 2 can be included)
Normal TSH levels
Normal 25-OH vitamin D levels (>/= 20 ng/ml) at baseline (subjects may be repleted)
Normal calcium levels
Normal renal function (creatinine \<2.0 mg/dl)
Well hydrated with adequate intake of liquids
Able to return for all follow-up visits
Capable of reading and understanding informed consent document
Males and females of childbearing potential must be willing and able to use double barrier method of contraception for 2 months after having received study drug

Exclusion criteria

Exclusion Criteria:

Have Paget's disease of the bone
Malignancy as a cause of acute SCI
Have unexplained high levels of alkaline phosphatase in blood
Any active gastrointestinal condition that results in malabsorption
Poor dental hygiene or requirement for invasive dental procedure within two months prior to enrollment
History of bone metastasis and skeletal malignancies
History of alcoholism or drug abuse within the 2 years prior to study screening
Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study
Elevated liver function tests >2x normal
Currently being prescribed anti-convulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator
Currently being prescribed glucocorticoids, other than inhaled glucocorticoids
Current or recent use any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds within 60 days of screening.
Pregnant, planning to become pregnant, or lactating

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 60 participants (actual)

Study arms

Experimental
Zol
Intravenous infusion of zoledronic acid (zol) 5 mg at baseline.
Drug: Zoledronic acid
Experimental
Placebo
Intravenous infusion of placebo at baseline.
Drug: Placebo

Interventions

DrugZoledronic acid
Intravenous infusion of zoledronic acid 5 mg.
Also known as: Reclast, Zometa, Bisphosphonate
DrugPlacebo
Placebo (saline) infusion to match zoledronic acid
Also known as: Saline

What researchers measure

Primary outcomes

Percent Change in Bone Mass Density (BMD) in the Hip
Percent change of bone mass density (BMD) in the total hip (as measured by DXA)
Time frame: 0-12 months
Percent Change of Bone Mass Density (BMD) in the Femoral Neck
Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA)
Time frame: 0-12 months

Secondary outcomes

Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur
Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT.
Time frame: 0-12 months
Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur
Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT
Time frame: 0-12 months

Results

Posted Jun 2, 2021

Limitations and caveats

The number of participants in the trial was limited, particularly during the second year in each subgroup. Additionally, the number of women studied was limited but was representative of the general sex distribution observed in people with spinal cord injury.

Participant flow

Patients with acute SCI were recruited from the Shirley Ryan AbilityLab, formerly known as the Rehabilitation Institute of Chicago. Recruitment took place between February 2015 and February 2018.

Participant flow — Overall Study
Milestone	Zoledronic Acid	Placebo
Started	30	30
Completed	22	24
Not completed	8	6
Withdrew: Withdrawal by subject	3	1
Withdrew: Lost to follow-up	5	5

Outcome measures

PrimaryPercent Change in Bone Mass Density (BMD) in the Hip

Percent change of bone mass density (BMD) in the total hip (as measured by DXA)

Time frame:: 0-12 months
Reported as:: Median · percent change in bone mass density

Percent Change in Bone Mass Density (BMD) in the Hip
percent change in bone mass density	Zoledronic Acid	Placebo
Percent Change in Bone Mass Density (BMD) in the Hip	-2.21 (-8.93 to 4.51)	-12.82 (-29.04 to 3.40)

Statistical analysis

Zoledronic Acid vs Placebo · Mixed Models Analysis · p = 0.05 · Median difference (final values): 10.61

PrimaryPercent Change of Bone Mass Density (BMD) in the Femoral Neck

Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA)

Time frame:: 0-12 months
Reported as:: Median · percent change in bone mass density

Percent Change of Bone Mass Density (BMD) in the Femoral Neck
percent change in bone mass density	Zoledronic Acid (Zol)	Placebo (Pla)
Percent Change of Bone Mass Density (BMD) in the Femoral Neck	-1.72 (-7.05 to 3.59)	-11.34 (-22.29 to -0.39)

SecondaryPercent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur

Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT.

Time frame:: 0-12 months
Reported as:: Median · percent change

Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur
percent change	Zoledronic Acid (Zol)	Placebo (Pla)
Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur	-9.6 (-31.02 to 11.82)	-22.90 (-50.72 to 4.92)

SecondaryPercent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur

Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT

Time frame:: 0-12 months
Reported as:: Median · percent change

Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur
percent change	Zoledronic Acid (Zol)	Placebo (Pla)
Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur	-4.73 (-13.83 to 4.37)	-8.88 (-19.12 to 1.36)

Adverse events

Collected over Baseline - 12 month visit. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Zoledronic Acid	0/30 (0%)	8/30 (26.7%)	28/30 (93.3%)
Placebo	0/30 (0%)	9/30 (30%)	22/30 (73.3%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Zoledronic Acid	Placebo
Urinary Tract InfectionRenal and urinary disorders	3/30	5/30
Acute Phase ResponseGeneral disorders	2/30	0/30
Autonomic DysreflexiaNervous system disorders	0/30	2/30
Altered Mental StatusPsychiatric disorders	1/30	0/30
C. difficile InfectionInfections and infestations	1/30	0/30
DehydrationMetabolism and nutrition disorders	0/30	1/30
ThrombusVascular disorders	0/30	1/30
EpilepsyNervous system disorders	1/30	0/30
Exophoria with Intermittent ExotropiaEye disorders	1/30	0/30
Gas (Incidental finding on X-ray)Musculoskeletal and connective tissue disorders	1/30	0/30

Most frequent other events

Showing 10 of 23

Most frequent other events
Event	Zoledronic Acid	Placebo
Acute Phase ResponseGeneral disorders	20/30	3/30
Urinary Tract InfectionRenal and urinary disorders	15/30	10/30
Upper Respiratory InfectionRespiratory, thoracic and mediastinal disorders	2/30	8/30
Joint PainMusculoskeletal and connective tissue disorders	2/30	4/30
Pressure UlcerSkin and subcutaneous tissue disorders	3/30	4/30
Autonomic DysreflexiaNervous system disorders	3/30	1/30
CoughGeneral disorders	3/30	0/30
FeverGeneral disorders	2/30	3/30
Heterotopic Ossification, new or worsenedMusculoskeletal and connective tissue disorders	3/30	2/30
HypertensionVascular disorders	3/30	2/30

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Zoledronic Acid	Placebo	Total
<=18 years	0	0	0
Between 18 and 65 years	29	28	57
>=65 years	1	2	3

Age, Continuous
Age, Continuous(years)	Zoledronic Acid	Placebo	Total
Mean	37.3 ± 15.9	38.2 ± 15.2	37.8 ± 15.4

Sex: Female, Male
Sex: Female, Male(Participants)	Zoledronic Acid	Placebo	Total
Female	9	3	12
Male	21	27	48

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Zoledronic Acid	Placebo	Total
Hispanic or Latino	4	7	11
Not Hispanic or Latino	26	23	49
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Zoledronic Acid	Placebo	Total
American Indian or Alaska Native	0	0	0
Asian	2	1	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	8	6	14
White	20	21	41
More than one race	0	2	2
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Zoledronic Acid	Placebo	Total
United States	30	30	60

Time Since Injury (Days)
Time Since Injury (Days)(days)	Zoledronic Acid	Placebo	Total
Mean	68.7 ± 28.5	62.7 ± 23.2	65.7 ± 25.9

Study locations

2 sites

Northwestern University Feinberg School of Medicine
Chicago, Illinois 60611, United States
Rehabilitation Institute of Chicago
Chicago, Illinois 60611, United States

References and documents

Publications

Edwards WB, Haider IT, Simonian N, Barroso J, Schnitzer TJ. Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial. J Bone Miner Res. 2021 Nov;36(11):2127-2138. doi: 10.1002/jbmr.4416. Epub 2021 Jul 29. PubMed 34278611 ↗
Haider IT, Lobos SM, Simonian N, Schnitzer TJ, Edwards WB. Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time. Osteoporos Int. 2018 Dec;29(12):2703-2715. doi: 10.1007/s00198-018-4733-0. Epub 2018 Oct 17. PubMed 30334093 ↗

Study documents

Study protocol · Jun 28, 2020
Statistical analysis plan · Jun 17, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 2, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02325414
Lead sponsor: Northwestern University
Collaborators: Congressionally Directed Medical Research Programs
Responsible party: Thomas J. Schnitzer (Professor, Northwestern University) — Principal investigator
First posted: Dec 25, 2014
Start date: Feb 2015
Primary completion: Aug 25, 2020
Completion: Aug 25, 2020
Results posted: Jun 2, 2021
Last update: Dec 2, 2025

Study contacts

Thomas J Schnitzer, MD, PhD

principal investigator · Northwestern University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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