Osteosarcoma of bone in apatient with primary hyperparathyroidism: a case report.

A 69-year-old woman was diagnosed with a malignant tumor of the right proximal femur. She had primary hyperparathyroidism and chronic elevation of parathyroid hormone levels (PTH > 1,000 pg/ml). She underwent resection of the bone lesion; histological analysis showed a high-grade fibroblastic osteosarcoma. In addition, she underwent curative resection of a large left superior parathyroid adenoma. To our knowledge, this is the third reported clinical case of osteosarcoma arising in association with hyperparathyroidism.

Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma. Brain metastases have been reported to be a common feature of Stage IV ASPS, and recent practice guidelines recommend routine intracranial imaging as part of the staging evaluation in all patients who present with ASPS. METHODS: The authors performed a comprehensive retrospective review of the clinical presentation, treatment, outcome, and patterns of failure in a consecutive series of patients with localized (American Joint Committee on Cancer [AJCC] Stages II/III) or metastatic (AJCC Stage IV) ASPS who presented to a tertiary care cancer center between 1959 and 1998. RESULTS: Seventy-four patients were identified from the database searches. The anatomic distribution of their primary tumors included: extremities, 44 patients (60%); trunk, 15 patients (20%); head and neck, 9 patients (12%); and retroperitoneum, 6 patients (8%). The median tumor size was 6.5 cm (range, 1.2-24 cm). The AJCC stage at presentation was Stage II or III in 35% of the patients and Stage IV in 65% of the patients. The 5-year actuarial local recurrence free, distant recurrence free, disease free, and overall survival rates among the 22 patients with localized ASPS were 88%, 84%, 71%%, and 87%, respectively. At a median follow-up of 9 years, 2 of 22 patients with localized disease had developed local recurrences and 3 had developed metastatic disease (all to the lung only). Brain metastases were noted in 9 of 48 patients who presented with Stage IV (M1) disease (19%) and always were noted in association with metastasis to other sites. The median survival of patients with M1 disease was 40 months, with a 5-year survival rate of 20%. CONCLUSIONS: Long term follow-up of patients with localized ASPS reveals a relatively indolent clinical course with relatively low rates of local and distant recurrence. In patients with Stage IV ASPS, brain metastases were observed only as part of more disseminated disease. The observations of the current study do not support current practice guidelines for the staging of patients with ASPS and suggest that selective rather than routine intracranial imaging should be used in patients presenting with ASPS.

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

The floating knee in the pediatric patient. Nonoperative versus operative stabilization.

The results of nonoperative and operative or rigid stabilization of ipsilateral femur and tibia fractures in children and adolescents were evaluated. Twenty-nine consecutive patients with open physes (30 affected extremities) were reviewed. Their mean followup was 8.6 years (range, 1.1-18.6 years). The nonoperative group consisted of 16 patients and 16 extremities treated by skeletal traction of the femoral fracture, closed reduction and splinting or casting of the tibia fractures, and eventual immobilization in a hip spica cast. The operative group, was comprised of 13 patients and 14 extremities in which one or both fractures were treated by open reduction and internal fixation, intramedullary fixation, or external fixation. Despite higher modified injury severity scores and skeletal injury scores, the patients who were treated operatively had a significantly reduced hospital stay, 20.1 days versus 34.9 days, respectively; decreased time to unsupported weightbearing, 16.8 weeks compared with 22.3 weeks, respectively; and fewer complications. Operative stabilization of the femur had a significant effect on decreasing the length of hospital stay and the time to unassisted weightbearing. The patients also were analyzed according to their age at the time of injury: 9 years of age or younger and 10 years of age and older. The younger children who were treated nonoperatively had an increased rate of lower extremity length discrepancy, angular malunion, and need for a secondary surgical procedure as compared with younger children who were treated operatively with rigid fixation. Based on the results of the current study, operative stabilization of at least the femur fracture and, preferably, both fractures in the treatment of a child with a floating knee is recommended, even for younger children.

Osteosarcoma in preadolescent patients.

The medical records of boys younger than 11 years and girls younger than 10 years of age with osteosarcoma of the pelvis or extremity were reviewed. Thirty patients were identified who were newly diagnosed but untreated for osteosarcoma. None of these patients had pulmonary metastases. The same four protocols were used to treat the patients in the current study as were used to treat adolescents. The event-free and overall survival was calculated and prognostic factors were assessed. The median followup time was 8 years (range, 6-14 years). The results were compared with the results of older patients treated with the same protocols and with published results. Fourteen patients had pulmonary metastases (47%); among these patients, four also had skeletal metastases (in two of the latter, skeletal metastases appeared before the pulmonary metastases). Event-free survival was 53% and overall survival was 57%. This result is comparable with current survival results in adolescent and older patients. Serum alkaline phosphatase and serum lactic dehydrogenase levels before treatment, height percentile greater than 50%, chemotherapy-induced tumor necrosis, surgical procedure, tumor site, tumor histologic features, and patient gender were not prognostic indicators. The prognosis for prepubertal patients with osteosarcoma is similar to the prognosis of their adolescent and older counterparts. There does not seem to be any indication to treat preadolescent patients with osteosarcoma using alternate therapies.

A revisit of MRI analysis for synovial sarcoma.

We evaluated magnetic resonance imaging (MRI) findings of synovial sarcomas in 22 patients, and the most common MRI findings were oval and well-defined nodular masses with heterogeneous intermediate signal intensity (SI) on T1 weighted images (WI), high SI on T2-WI and heterogeneous contrast enhancement. A cystic component was seen in 77%, intratumoral hemorrhage in 73%, and calcification in three monophasic sarcomas. Metastases were noted in lung (mostly biphasic type), lymph node, and bone. Posttreatment changes revealed diffusely increased S1 on T2-W1 and slightly diffuse contrast enhancement with feathery appearance. Morphology and MR signal characteristics assist in synovial sarcoma management.

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.

Synthetic biodegradable polymers for orthopaedic applications.

Synthetic biodegradable polymers offer an alternative to the use of autografts, allografts, and nondegradable materials for bone replacement. They can be synthesized with tailored mechanical and degradative properties. They also can be processed to porous scaffolds with desired pore morphologic features conducive to tissue ingrowth. Moreover, functionalized polymers can modulate cellular function and induce tissue ingrowth. This review focuses on four classes of polymers that hold promise for orthopaedic applications: poly alpha-hydroxy esters, polyphosphazenes, polyanhydrides, and polypropylene fumarate crosslinked networks.

Crosslinking characteristics of an injectable poly(propylene fumarate)/beta-tricalcium phosphate paste and mechanical properties of the crosslinked composite for use as a biodegradable bone cement.

We investigated the crosslinking characteristics of an injectable composite paste of poly(propylene fumarate) (PPF), N-vinyl pyrrolidinone (N-VP), benzoyl peroxide (BP), sodium chloride (NaCl), and beta-tricalcium phosphate (beta-TCP). We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and NaCl weight percent on the crosslinking temperature, heat release upon crosslinking, gel point, and the composite compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38 degrees and 48 degrees C, which was much lower than that of 94 degrees C for poly(methyl methacrylate) bone cement controls tested under the same conditions. The total heat released upon crosslinking was decreased by an increase in PPF molecular weight and a decrease in N-VP/PPF ratio. The gel point was affected strongly by the PPF molecular weight, with a decrease in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The time frame for curing was varied from 1-121 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF, increasing NaCl content, and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 1 and 12 MPa, and the compressive modulus values fell between 23 and 265 MPa. These data suggest that injectable PPF/beta-TCP pastes can be prepared with handling characteristics appropriate for clinical orthopedic applications and that the mechanical properties of the cured composites are suitable for trabecular bone replacement.

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair.

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.

Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field.

PURPOSE: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma. METHODS: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2). RESULTS: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively. CONCLUSION: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.

Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up.

BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue sarcoma and presents a wide spectrum of clinical behavior. The authors examined the correlation among histologic subtypes, outcomes, and patterns of recurrence among patients with extremity liposarcomas. METHODS. A retrospective review of all patients with intermediate and high grade extremity liposarcoma referred to the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to December 31, 1992, was performed. Data on clinical presentation, treatment, patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13-year study period, 122 patients with intermediate or high grade extremity liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There were no differences between the myxoid and pleomorphic subtype groups in tumor size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The median follow-up was 70 months. The 5-year overall survival rate for all intermediate and high grade extremity liposarcoma patients presenting with primary disease (n=85) was 74%; the 5-year local recurrence free survival, distant recurrence free survival, and disease free survival rates were 93%, 78%, and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft tissue of the back), and 2 were to the lung only. Among the 18 patients with pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary sites and did so significantly more frequently than pleomorphic tumors. Imaging of the abdomen, retroperitoneum, and extrapleural chest should be performed for accurate staging and posttreatment follow-up of patients with myxoid liposarcoma. Patients presenting with "primary" myxoid liposarcoma of the trunk should be carefully evaluated for an occult primary tumor in an extremity.

Polymer concepts in tissue engineering.

Traumatic injuries, cancer treatment, and congenital abnormalities are often associated with abnormal bone shape or segmental bone loss. Restoration of normal structure and function in these cases requires replacement of the missing bone that may be accomplished by surgical transfer of natural tissue from an uninjured location elsewhere in the body. However, this procedure is limited by availability, adequate blood supply, and secondary deformities at the donor site. One strategy to overcome these problems is to develop living tissue substitutes based on synthetic biodegradable polymers. Three methods of bone regeneration using biodegradable polymers are being studied in our laboratory: tissue induction, cell transplantation, and fabrication of vascularized bone flaps. Injectable polymers are used for filling skeletal defects and guiding bone tissue growth. Their main advantage is minimizing the surgical intervention or the severity of the surgery. Polymer-cell constructs also hold great promise in the field of tissue engineering. They provide a scaffold on which cells grow and organize themselves. As the cells begin to secrete their own extracellular matrix, the polymer degrades and is eventually eliminated from the body, resulting in completely natural tissue replacement. Bone flaps can be fabricated ectopically into precise shapes and sizes. With an attached vascular supply, these flaps can be transferred into areas deficient in vascularity. This article discusses polymer concepts regarding bone tissue engineering and reviews recent advances of our laboratory on guided bone regeneration using biodegradable polymer scaffolds.

Soft tissue reconstruction following hemipelvectomy.

BACKGROUND: Resection of primary and metastatic pelvic bone disease may result in large soft tissue deficits. Guidelines for soft tissue reconstruction following pelvic bone resection were evaluated in a retrospective study. METHODS: Over a 5-year period 21 patients (31%) required soft tissue reconstruction following pelvic bone resection. Data on these patients were retrieved from case records. RESULTS: Twelve patients underwent immediate, planned reconstruction, 1 a two-stage reconstruction, and 8 patients required a delayed procedure for complications after bone resection and primary closure. Soft tissue reconstruction was usually accomplished with muscle-based flaps; (25 flaps in 20 patients: 20 pedicled, 5 free), or with skin grafts alone (1 patient). Specific postreconstruction complications occurred in 9 patients, 5 in flaps based on the ipsilateral rectus muscle. CONCLUSION: Flap closure is indicated to achieve primary closure and eliminate deadspace. The ipsilateral rectus muscle should be used with caution and contralateral-based rectus flaps considered. Indications for free flaps include the size and location of the defect and availability of tissue from an amputated limb.

In vivo degradation of a poly(propylene fumarate)/beta-tricalcium phosphate injectable composite scaffold.

This study was designed to investigate the in vivo biodegration and biocompatibility of a poly(propylene fumarate) (PPF)-based orthopedic biomaterial. The effects of varying the PPF to N-vinyl pyrrolidinone ratio and PPF to beta-tricalcium phosphate content were studied. The composite mechanical properties and local tissue interactions were analyzed over 12 weeks. An initial increase in both compressive modulus and strength was seen for composite formulations that incorporated beta-tricalcium phosphate. The samples incorporating a higher PPF to N-vinyl pyrrolidinone ratio reached a maximal compressive strength of 7.7 MPa and a maximal compressive modulus of 191.4 MPa at 3 weeks. The lower PPF to N-vinyl pyrrolidinone ratio samples gained a maximum compressive strength of 7.5 MPa initially and a compressive modulus of 134.0 MPa at 1 week. At 6 weeks, all samples for formulations incorporating beta-tricalcium phosphate crumbled upon removal and were not mechanically tested. Samples that did not incorporate beta-tricalcium phosphate were very weak and insufficient for bone replacement at the 4-day time point and beyond. Tissue interactions resulted in a mild inflammatory response at the initial time points and mature fibrous encapsulation by 12 weeks.

Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone).

We retrospectively studied the outcome of percutaneous needle biopsy and intralesional injection of a corticosteroid (methylprednisolone) in thirty-nine patients who had localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). All thirty-nine patients had a solitary symptomatic lesion at presentation; a second lesion developed in two patients, two and four months after the first lesion was diagnosed. Therefore, there were forty-one lesions in thirty-nine patients. Fine-needle aspiration with or without core-needle biopsy was performed for all forty-one lesions, and the diagnosis of Langerhans-cell histiocytosis was established for thirty-seven (90 per cent). A corticosteroid was injected into thirty-five lesions. Twenty-nine received the injection at the time of the fine-needle aspiration on the basis of the cytological findings in the aspirate. Six patients who had a solitary lesion had a two-stage procedure because the injection was delayed until the diagnosis was confirmed with histological evaluation of specimens obtained by core-needle biopsy. Thirty-four (97 per cent) of the thirty-five lesions healed. The clinical symptoms associated with thirty-one lesions resolved within two weeks after a single injection of the corticosteroid. There were no complications associated with either the biopsy or the injection. At a median of ninety months (range, twenty-four to 199 months), no patient had recurrence of symptoms or of radiographic evidence of the lesion. All patients who had been managed with an intralesional injection of the corticosteroid had full range of motion of the affected extremity and had resumed unlimited activities. Although the mechanism of action of intralesional injection of a corticosteroid has not been defined, use of percutaneous needle biopsy to diagnose localized Langerhans-cell histiocytosis and treatment with intralesional administration of methylprednisolone relieved pain expeditiously, enabled the patient to avoid an operative procedure, and resulted in osseous healing. The specific role of corticosteroid therapy remains to be determined by prospective, randomized studies.

Giant-cell tumor of the tendon sheath arising from the posterior cruciate ligament of the knee: a case report and review of the literature.

The localized form of a giant-cell tumor of the tendon sheath is uncommon and rarely intraarticular. While the sonographic findings are nonspecific, the magnetic resonance (MR) findings can be diagnostic. Relatively homogeneous iso- or marginal hyperintensity on T2-weighted sequences, lack of susceptibility effects due to hemosiderin, the demonstration of a fibrous capsule and the absence of adjacent joint involvement may help to differentiate localized and diffuse forms of giant-cell tumors of tendon sheaths and pigmented villonodular synovitis.

Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery.

Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.