Comparing Synthetic Bone Alone Versus Synthetic Bone With Bone Marrow in Bone Lesions

• Sponsor: State University of New York - Upstate Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00147823
• Collaborator: Orthovita d/b/a Stryker (Industry)
• Enrollment: 63
• Location: 1
• Arms: 2
• Duration (Months): 84
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is a prospective randomized study comparing Vitoss alone versus Vitoss with bone marrow aspirate in benign bone lesions.

Condition or Disease	Intervention/Treatment	Phase
Bone Diseases	Device: Vitoss Alone; Device: Vitoss with Bone Marrow Aspirate	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Randomized Study Comparing Vitoss Alone Versus Vitoss With Bone Marrow Aspirate in Benign Bone Lesions
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitoss with bone marrow aspirate Addition of Vitoss to the bone marrow aspirate	Device: Vitoss with Bone Marrow Aspirate; Vitoss mixed with Bone Marrow aspirate
Active Comparator: Vitoss Alone vitoss alone	Device: Vitoss Alone; Synthetic bone graft material

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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. .

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SUNY Upstate Medical University	Syracuse	New York	United States	13210

Sponsors and Collaborators

• State University of New York - Upstate Medical University
• Orthovita d/b/a Stryker

Investigators

• Principal Investigator: Timothy A. Damron, M.D., State University of New York - Upstate Medical University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Paper written in 2002 when study first began

Publications

None provided.

• Responsible Party: Timothy Damron, M.D., Associate Professor, State University of New York - Upstate Medical University
• ClinicalTrials.gov Identifier: NCT00147823
• Other Study ID Numbers: SUNY UMU IRB # 5130
• First Posted: Sep 7, 2005
• Last Update Posted: Jun 8, 2015
• Last Verified: Dec 1, 2013

• Keywords provided by Timothy Damron, M.D., Associate Professor, State University of New York - Upstate Medical University: Bone formation; Bone lesions; Benign bone lesion
• Additional relevant MeSH terms: Bone Diseases

Study Results

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

Arm/Group Title	Vitoss Alone	Vitoss With Bone Marrow Aspirate
Arm/Group Description	No bone marrow aspirate used	Addition of Vitoss to the bone marrow aspirate Vitoss : Synthetic bone graft material
Period Title: Overall Study
STARTED	32	31
Week 6 Visit	26	28
Month 3 Visit	25	24
Month 6 Visit	25	21
Month 12 Visit	21	25
Month 12 CT Scan	20	25
Month 18 Visit	21	20
Month 24 Visit	21	18
COMPLETED	19	16
NOT COMPLETED	13	15

Baseline Characteristics

Arm/Group Title	Vitoss Used With Bone Marrow Aspirate	Vitoss Only	Total
Arm/Group Description	Vitoss: Synthetic bone graft material mixed with Bone Marrow aspirate	Vitoss: Synthetic bone graft material alone	Total of all reporting groups
Overall Participants	31	32	63
Age (Count of Participants)
<=18 years	16 51.6%	14 43.8%	30 47.6%
Between 18 and 65 years	15 48.4%	17 53.1%	32 50.8%
>=65 years	0 0%	1 3.1%	1 1.6%
Sex: Female, Male (Count of Participants)
Female	15 48.4%	15 46.9%	30 47.6%
Male	16 51.6%	17 53.1%	33 52.4%
Region of Enrollment (participants) [Number]
United States	31 100%	32 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Resorption of Graft Material (GR) Compared at 24 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this timepoint.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	18	19
Mean (Full Range) [percentage of resorption]	51	47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitoss, Vitoss Alone
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	ANOVA
	Comments	Using baseline (6 wk) and two year post operative predicted effects data, and setting desirable power to detect our effects to 80%

2. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 24 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	18	19
Mean (Full Range) [percentage of trabeculation]	95	98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitoss, Vitoss Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Chi-squared, Corrected
	Comments

3. Other Pre-specified Outcome

Title	Resorption of Graft Material (GR) Compared at 18 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	17	17
Mean (Full Range) [percentage of resorption]	47	44

4. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 18 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	17	17
Mean (Full Range) [percentage of trabeculation]	90	90

5. Other Pre-specified Outcome

Title	Resorption of Graft Material (GR) Compared at 12 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	23	19
Mean (Full Range) [percentage of resorption]	45	42

6. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 12 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	23	19
Mean (Full Range) [percentage of trabeculation]	42	47

7. Other Pre-specified Outcome

Title	Resorption of Graft Material (GR) Compared at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	19	24
Mean (Full Range) [percentage of resorption]	28	25

8. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	19	24
Mean (Full Range) [percentage of trabeculation]	31	33

9. Other Pre-specified Outcome

Title	Resorption of Graft Material (GR) Compared at 3 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	21	25
Mean (Full Range) [percentage of resorption]	18	22

10. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 3 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	21	25
Mean (Full Range) [percentage of trabeculation]	8	10

11. Other Pre-specified Outcome

Title	Resorption of Graft Material (GR) Compared at 6 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	27	25
Mean (Full Range) [percentage of resorption]	6	8

12. Other Pre-specified Outcome

Title	Bone Trabeculation Through the Defect (BT) Compared at 6 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed, refers to the number of participants who completed follow up or had radiographs taken at this time point.

Arm/Group Title	Vitoss	Vitoss Alone
Arm/Group Description	Addition of Vitoss to the bone marrow aspirate Vitoss: Synthetic bone graft material	Vitoss alone, not bone marrow aspirate used
Measure Participants	27	25
Mean (Full Range) [percentage of trabeculation]	4	7

Adverse Events

Time Frame	6 week, 3, 6, 12, 18 and 24 months
Adverse Event Reporting Description	Subjects were asked at their office visits if they had any new complications, any new diagnosis/treatments, also if records were received from another physician, this information was collected.
Arm/Group Title	Vitoss Without Bone Marrow Aspirate		Vitoss With Bone Marrow Aspirate
Arm/Group Description	subjects who received Vitoss without bone marrow aspirate		subjects who received Vitoss with bone marrow aspirate
All Cause Mortality
	Vitoss Without Bone Marrow Aspirate		Vitoss With Bone Marrow Aspirate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitoss Without Bone Marrow Aspirate		Vitoss With Bone Marrow Aspirate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Vitoss Without Bone Marrow Aspirate		Vitoss With Bone Marrow Aspirate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/32 (34.4%)		14/31 (45.2%)
Blood and lymphatic system disorders
hematoma	0/32 (0%)	0	1/31 (3.2%)	1
Musculoskeletal and connective tissue disorders
Knee pain-persistent	2/32 (6.3%)	2	2/31 (6.5%)	2
recurrence of cyst	1/32 (3.1%)	1	2/31 (6.5%)	2
fracture of wrist	1/32 (3.1%)	1	0/31 (0%)	0
low back pain	1/32 (3.1%)	1	0/31 (0%)	0
bilateral leg weakness	1/32 (3.1%)	1	0/31 (0%)	0
femur pain	0/32 (0%)	0	1/31 (3.2%)	1
hip pain	0/32 (0%)	0	1/31 (3.2%)	1
shoulder pain	0/32 (0%)	0	1/31 (3.2%)	1
cervical neuropathy	0/32 (0%)	0	1/31 (3.2%)	1
fracture of shoulder through lesion	1/32 (3.1%)	1	0/31 (0%)	0
fracture of femur through lesion	0/32 (0%)	0	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia	2/32 (6.3%)	2	0/31 (0%)	0
Skin and subcutaneous tissue disorders
drainage at incision	2/32 (6.3%)	2	3/31 (9.7%)	3
rash at incision	0/32 (0%)	0	1/31 (3.2%)	1

Limitations/Caveats

Limitation due to incomplete follow up by subjects or unavailability of radiographs. Also difficulties in assessing the outcomes of resorption if lesions were small or there was artifact from hardware in the area.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.