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Bone Formation in Transplants of Human Bone Marrow Stromal Cells and Hydroxyapatite–Tricalcium Phosphate: Prediction with Quantitative CT in Mice¹

¹ From the Division of Plastic Surgery, Department of Surgery, University of California–San Francisco, San Francisco General Hospital, 1001 Potrero Ave, Ward 3A, San Francisco, CA 94110 (M.H.M.); Craniofacial and Skeletal Diseases Branch (S.A.K., P.G.R.) and Biostatistics Core, Office of the Director (A.K.), National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md; Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, Md (N.A.A.). Received September 14, 2001; revision requested October 23; final revision received May 23, 2003; accepted June 18. Address correspondence to M.H.M. (e-mail: mmankani@sfghsurg.ucsf.edu).

PURPOSE: To determine whether quantitative computed tomography (CT) can be used to estimate the extent of new bone formation in hydroxyapatite–tricalcium phosphate (HA-TCP)–based transplants.

MATERIALS AND METHODS: Bone-forming transplants were generated by attaching cultured human bone marrow stromal cells to aliquots of HA-TCP particles and were placed in subcutaneous pockets in immunocompromised mice. After 8 weeks, the transplants were individually imaged; each scan included a phantom. Overall bone mineral density (BMD) of each transplant was obtained. Hematoxylin-eosin–stained sections of the same transplants were then examined histologically, which is the reference standard for assessing bone formation. The extent of bone in each transplant was scored on a semiquantitative scale ranging from 0 to 4 by three independent blinded observers; the bone score for each transplant was calculated by averaging the three observer scores. BMD was compared with the histologically determined bone score for each transplant. Statistical evaluations included (a) calculation of empiric receiver operating characteristic curves to determine optimum BMD thresholds and (b) determination of the relationship between BMD and bone score, including derivation of Pearson correlation coefficients.

RESULTS: One hundred twenty transplants were evaluated. Average BMD of 600 mg/cm³ K₂HPO₄ or more was noted in transplants with appreciable bone formation (bone score 3), while average BMD of less than 600 mg/cm³ K₂HPO₄ was seen in transplants with poor bone formation (bone score < 3) (P < .001). Among transplants with appreciable bone formation, the BMD was proportional to the extent of mineralized matrix present in the new bone.

CONCLUSION: Use of quantitative CT offers a practical approach for the noninvasive determination of new bone formation in mineralizing bone marrow stromal cells and HA-TCP transplants.

© RSNA, 2004

Index terms: Animals • Bone marrow, transplantation • Bones, CT, 40.12119 • Computed tomography (CT), quantitative, 40.12119 • Hydroxyapatite • Phantoms

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