Disuse Osteoporosis
Conditions
Keywords
Spinal Cord Injury, Disuse Osteoporosis, Zoledronic acid, Bisphosphonates, Dual Energy X-ray Absorptiometry
Brief summary
In subjects with acute SCI: To compare the effects of parenteral zoledronic acid therapy on preservation of regional and total skeletal mass (DXA). Hypothesis: Zoledronic acid will dramatically diminish bone loss in persons with acute SCI, as evidenced by serial densitometry determinations (DXA).
Detailed description
Immobilization is associated with disuse osteoporosis. Spinal cord injury (SCI) produces a syndrome of acute skeletal immobilization with immediate and irreversible unloading of the involved skeletal regions resulting in accelerated bone loss. In addition to rapid bone loss, there are also the complications of hypercalciuria, hypercalcemia, nephrolithiasis, and renal insufficiency. In some reports, as much as 50% of regional bone mass has been lost within the first year after paralysis. A depletion of regional bone of such magnitude greatly increases the risk of fractures, with associated morbidity and increased cost of care. Often, these fractures occur with minimal or non-obvious trauma and may pass undiagnosed for varying lengths of time due to the absence of pain sensation. The acute complications of fracture may include hemorrhage, deep venous thrombosis, and autonomic dysreflexia. Long-term complications include functional deformity, non-union, infection, heterotopic calcification, and significantly longer healing time. The sociology-economic consequences include a minimum of 1 to 2 weeks of hospitalization and the potential need for an increased level of attendant care. This study will address the efficacy of a bisphosphonate, zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ), in the prevention of the bone loss associated with acute SCI. Prevention of regional osteoporosis in persons with SCI would reduce the morbidity associated with fractures, a known secondary complication of immobilization. Thus, the quality of life would be improved in terms of employment responsibilities (reduction in days absent from employment and income lost) and personal activities (recreational endeavors, independence, and ease in which one performs activities of daily living). Individuals with SCI may then engage more securely in activities without fear of fracture, a tremendous psychological benefit.
Interventions
DRUGZoledronic acid
At baseline, study subjects in the treatment group will receive 5 mg of zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ) by intravenous infusion over 30 minutes.
Sponsors
Kessler Institute for Rehabilitation
James J. Peters Veterans Affairs Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
1. Within 3 months of the date of acute SCI. 2. Motor-complete and incomplete SCI \[American Spinal Injury Association Impairment Scale (AIS) of sensorimotor impairment (AIS A, B, and C)\]
Exclusion criteria
1. Extensive life-threatening injuries (in addition to SCI) 2. Femur or tibia fracture or extensive bone trauma 3. History of prior bone disease (Paget's disease, overactive parathyroid, osteoporosis) 4. Post-menopausal women 5. Known allergy to bisphosphonates 6. Severe underlying chronic illness 7. Current diagnosis of cancer or history of cancer 8. I am currently receiving corticosteroids 9. Pregnancy or lactation 10. I have been diagnosed with kidney problems 11. As determined from the prescreening blood tests by the study physician Serum creatinine \> 2.0 mg/dl 12. As determined from the prescreening blood tests by the study physician Corrected calcium \< 8 mg/dl or \> 11 mg/dl 13. As determined from the prescreening blood tests by the study physician Elevated liver function enzymes \> 2 x upper limit of normal (ULN) 14. I am taking a bisphosphonate for heterotopic ossification (HO) (an overgrowth of bone typically diagnosed shortly after SCI in the pelvic region) 15. I have an existing dental condition or dental infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | Baseline and 12 months | An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the distal femur and proximal tibia by using a customized research software program supplied by the manufacturer. This measurement will be the primary determinant (dependent measure) of difference among the treatment and control groups, and they will be followed over time at the previously specified time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | Baseline and 12 months | An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid At baseline, study subjects in the treatment group will receive 5 mg of zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ) by intravenous infusion over 30 minutes. | 8 |
| No Treatment Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. | 13 |
| Total | 21 |
Baseline characteristics
| Characteristic | Zoledronic Acid | No Treatment | Total |
|---|---|---|---|
| Age, Continuous | 25.5 years STANDARD_DEVIATION 9.6 | 33.0 years STANDARD_DEVIATION 11 | 29.3 years STANDARD_DEVIATION 20.7 |
| Region of Enrollment United States | 8 participants | 13 participants | 21 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 0 / 13 |
| serious Total, serious adverse events | 3 / 8 | 1 / 13 |
Outcome results
Primary
Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12.
An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the distal femur and proximal tibia by using a customized research software program supplied by the manufacturer. This measurement will be the primary determinant (dependent measure) of difference among the treatment and control groups, and they will be followed over time at the previously specified time points.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | Baseline Distal Femur | 1.102 g/cm2 | Standard Deviation 0.148 |
| Zoledronic Acid | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | 12 Month Distal Femur | 0.898 g/cm2 | Standard Deviation 0.128 |
| Zoledronic Acid | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | Baseline Proximal Tibia | 1.274 g/cm2 | Standard Deviation 0.245 |
| Zoledronic Acid | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | 12 Month Proximal Tibia | 1.022 g/cm2 | Standard Deviation 0.267 |
| No Treatment | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | 12 Month Proximal Tibia | 1.237 g/cm2 | Standard Deviation 0.276 |
| No Treatment | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | Baseline Distal Femur | 1.134 g/cm2 | Standard Deviation 0.244 |
| No Treatment | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | Baseline Proximal Tibia | 1.341 g/cm2 | Standard Deviation 1.216 |
| No Treatment | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | 12 Month Distal Femur | 1.038 g/cm2 | Standard Deviation 0.241 |
Secondary
Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12
An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | Baseline Total Hip | 1.125 g/cm2 | Standard Deviation 0.166 |
| Zoledronic Acid | Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | 12 Month Total Hip | 1.042 g/cm2 | Standard Deviation 0.168 |
| No Treatment | Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | Baseline Total Hip | 1.020 g/cm2 | Standard Deviation 0.154 |
| No Treatment | Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | 12 Month Total Hip | 0.814 g/cm2 | Standard Deviation 0.151 |