Bone Diseases
Conditions
Keywords
Bone formation, Bone lesions, Benign bone lesion
Brief summary
This is a prospective randomized study comparing Vitoss alone versus Vitoss with bone marrow aspirate in benign bone lesions.
Detailed description
Bone graft obtained from a patient's own bone (autogenous), usually around the pelvis, is currently considered the gold standard for bone grafting material. It provides a structural scaffold on which the patient's own bone may grow into (osteoconduction), growth factors that can stimulate healing (osteoinduction), and primitive cells (progenitors) that can stimulate bone formation directly (osteogenesis). It readily regains a blood supply from the surrounding tissues (revascularization) and is incorporated into the recipient site. However, there are significant disadvantages in the use of the patient's own bone graft including complications where the bone is taken from (donor site morbidity), limited availability and expense. For defects created by scraping (curettage) of non-cancerous (benign) bone lesions, a structural scaffold (osteoconduction) is generally considered the minimal necessary role that the graft material must serve to allow healing of the defect. Hence, human donor bone procured at the time of death (allografts) and synthetic bone fillers have been used as an alternative to the patient's own bone (autogenous bone graft). The question that remains is whether additional growth factors that can stimulate bone formation (osteoinductive property) and/or cells that form bone directly (osteogenic property) facilitate healing of these defects when added to a material other than the patient's own bone graft source. In our experience with the use of the synthetic bone graft substitute ultraporous beta-tricalcium phosphate (TCP) (Vitoss, Orthovita, Inc.) over the last 3 years, the graft material, when combined with local blood alone, has performed well clinically but has persisted for a year or longer radiographically in some cases. Prolonged persistence of the graft material may serve as a potential stress riser, although we did not observe any untoward late effects in our published work. Several authors have studied the effects of composite grafts formed from a combination of bone graft substitutes and the patient's own bone marrow in animal models with promising results. There are no studies in the current literature evaluating the effects of healing in composite ultraporous beta-tricalcium phosphate and bone marrow aspirate (BMA) in defects after scraping of benign tumors (cavitary defects) in humans. The purpose of this study is to prospectively examine healing of cavitary defects treated with TCP alone versus those treated with TCP combined with BMA. Our hypothesis is that both graft resorption and trabeculation (radiographic measures of incorporation of the synthetic material by the native bone) will be more advanced at each time point in those patients that receive BMA plus TCP compared to those that receive TCP alone. Patients with any type of benign bone lesion indicated for surgical curettage would be offered inclusion in the study and followed for a minimum of 2 years post-operatively. Bone marrow aspiration would be obtained by a needle inserted through the skin (percutaneous aspiration) from the large bone of the pelvis (iliac crest) using a standard bone marrow aspiration needle. Patients with infection, bone marrow disorders, or other conditions that preclude use of supplementary the patient's bone marrow as well as those who prefer to use their own bone graft material (autograft) or donated human bone graft (allograft) alone would be excluded. Each patient will undergo radiographic evaluation of the lesion at 6 weeks, 3 months, 6 months, 1 year, 18 months and 2 years post operatively. At one time point (1 year) a computerized tomogram (CT) of the grafted region will be obtained for each patient. Two qualified, blinded, independent reviewers will evaluate the radiographs and CT scans for six criteria: 1. presence of graft within the soft tissues, 2. presence of a rim of radiolucency surrounding the grafted defect, 3. size/circumference of the rim of radiolucency, 4. resorption of graft material, 5. trabeculation through the defect and 6. persistence of graft material in the lesion. Kappa statistics have shown good agreement for these parameters in our retrospective preliminary analysis of results for the TCP use without bone marrow over the first 2 years of its use by the PI.
Interventions
DEVICEVitoss Alone
Synthetic bone graft material
DEVICEVitoss with Bone Marrow Aspirate
Vitoss mixed with Bone Marrow aspirate
Sponsors
Orthovita d/b/a Stryker
State University of New York - Upstate Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with a benign bone lesion requiring surgical curettage
Exclusion criteria
* Patients with infection, bone marrow disorders, or other contraindications to use of supplemental bone marrow aspiration as well as those who prefer autologous or allogeneic graft material alone (without synthetic filler) would be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resorption of Graft Material (GR) Compared at 24 Months | 24 months | Percentage of graft material that is resorbed (disappears) from area of incorporation, at 24 months .Participants were seen 24 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Resorption of Graft Material (GR) Compared at 18 Months | 18 months | Percentage of graft material that is resorbed (disappears) from area of incorporation at 18 months. Participants were seen 18 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
| Resorption of Graft Material (GR) Compared at 6 Weeks | 6 weeks | Percentage of graft material that is resorbed (disappears) from area of incorporation at 6 weeks. Participants were seen 6 week follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
| Bone Trabeculation Through the Defect (BT) Compared at 18 Months | 18 months | Bone trabeculation through the bone lesion at 18 months with reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs. |
| Resorption of Graft Material (GR) Compared at 12 Months | 12 months | Percentage of graft material that is resorbed (disappears) from area of incorporation at 12months. Participants were seen 12 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
| Bone Trabeculation Through the Defect (BT) Compared at 12 Months | 12 months | Bone trabeculation through the bone lesion at 12 months was reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs. |
| Bone Trabeculation Through the Defect (BT) Compared at 24 Months | 24 months | Bone trabeculation through the bone lesion at 24 months as determined with radiographs. There were several participants with incomplete follow up or incomplete radiographs. . |
| Bone Trabeculation Through the Defect (BT) Compared at 6 Months | 6 months | Bone trabeculation through the bone lesion at 6 months was reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs. |
| Resorption of Graft Material (GR) Compared at 3 Months | 3 months | Percentage of graft material that is resorbed (disappears) from area of incorporation at 3 months. Participants were seen 3 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
| Bone Trabeculation Through the Defect (BT) Compared at 3 Months | 3 months | Bone trabeculation through the bone lesion compared at 3 months were reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs. |
| Bone Trabeculation Through the Defect (BT) Compared at 6 Weeks | 6 weeks | Bone trabeculation through the bone lesion compared at 6 weeks were reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs. |
| Resorption of Graft Material (GR) Compared at 6 Months | 6 months | Percentage of graft material that is resorbed (disappears) from area of incorporation at 6 months. Participants were seen 6 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken. |
Countries
United States
Participant flow
Recruitment details
Subjects seen by Dr. Damron in his clinical office were asked to participate, if they met the inclusion/exclusion criteria. Dates of recruitment February 2005, through August 2007
Participants by arm
| Arm | Count |
|---|---|
| Vitoss Used With Bone Marrow Aspirate Vitoss: Synthetic bone graft material mixed with Bone Marrow aspirate | 31 |
| Vitoss Only Vitoss: Synthetic bone graft material alone | 32 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive vitoss due to infection | 6 | 2 |
| Overall Study | Lost to Follow-up | 6 | 12 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Vitoss Used With Bone Marrow Aspirate | Vitoss Only |
|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 16 Participants | 14 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 15 Participants | 17 Participants |
| Region of Enrollment United States | 63 participants | 31 participants | 32 participants |
| Sex: Female, Male Female | 30 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 33 Participants | 16 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 32 | 14 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 |
Outcome results
Primary
Resorption of Graft Material (GR) Compared at 24 Months
Percentage of graft material that is resorbed (disappears) from area of incorporation, at 24 months .Participants were seen 24 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 24 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 24 Months | 51 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 24 Months | 47 percentage of resorption |
Comparison: The sample size provided at least 80% power at a 5% alpha level to detect a medium to large effect in patients receiving Vitoss alone compared to combination therapy consisting of Vitoss with Bone Marrow Aspirate. Since a random coefficients model was used to analyze the data, the sample size calculation was estimated under this model assuming a 3% attrition rate between all measurement times.p-value: <0.01ANOVA
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 12 Months
Bone trabeculation through the bone lesion at 12 months was reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs.
Time frame: 12 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 12 Months | 42 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 12 Months | 47 percentage of trabeculation |
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 18 Months
Bone trabeculation through the bone lesion at 18 months with reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs.
Time frame: 18 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 18 Months | 90 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 18 Months | 90 percentage of trabeculation |
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 24 Months
Bone trabeculation through the bone lesion at 24 months as determined with radiographs. There were several participants with incomplete follow up or incomplete radiographs. .
Time frame: 24 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 24 Months | 95 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 24 Months | 98 percentage of trabeculation |
p-value: <0.01Chi-squared, Corrected
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 3 Months
Bone trabeculation through the bone lesion compared at 3 months were reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs.
Time frame: 3 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 3 Months | 8 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 3 Months | 10 percentage of trabeculation |
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 6 Months
Bone trabeculation through the bone lesion at 6 months was reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs.
Time frame: 6 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 6 Months | 31 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 6 Months | 33 percentage of trabeculation |
Other Pre-specified
Bone Trabeculation Through the Defect (BT) Compared at 6 Weeks
Bone trabeculation through the bone lesion compared at 6 weeks were reviewed with radiographs. There were several participants with incomplete follow up or incomplete radiographs.
Time frame: 6 weeks
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Bone Trabeculation Through the Defect (BT) Compared at 6 Weeks | 4 percentage of trabeculation |
| Vitoss Alone | Bone Trabeculation Through the Defect (BT) Compared at 6 Weeks | 7 percentage of trabeculation |
Other Pre-specified
Resorption of Graft Material (GR) Compared at 12 Months
Percentage of graft material that is resorbed (disappears) from area of incorporation at 12months. Participants were seen 12 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 12 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 12 Months | 45 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 12 Months | 42 percentage of resorption |
Other Pre-specified
Resorption of Graft Material (GR) Compared at 18 Months
Percentage of graft material that is resorbed (disappears) from area of incorporation at 18 months. Participants were seen 18 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 18 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 18 Months | 47 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 18 Months | 44 percentage of resorption |
Other Pre-specified
Resorption of Graft Material (GR) Compared at 3 Months
Percentage of graft material that is resorbed (disappears) from area of incorporation at 3 months. Participants were seen 3 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 3 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 3 Months | 18 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 3 Months | 22 percentage of resorption |
Other Pre-specified
Resorption of Graft Material (GR) Compared at 6 Months
Percentage of graft material that is resorbed (disappears) from area of incorporation at 6 months. Participants were seen 6 month follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 6 months
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 6 Months | 28 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 6 Months | 25 percentage of resorption |
Other Pre-specified
Resorption of Graft Material (GR) Compared at 6 Weeks
Percentage of graft material that is resorbed (disappears) from area of incorporation at 6 weeks. Participants were seen 6 week follow with radiographs to review resorption of graft material. There a several that had incomplete follow up or radiographs not taken.
Time frame: 6 weeks
Population: Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitoss | Resorption of Graft Material (GR) Compared at 6 Weeks | 6 percentage of resorption |
| Vitoss Alone | Resorption of Graft Material (GR) Compared at 6 Weeks | 8 percentage of resorption |