Nigel Colterjohn

Procurement of Bone Graft from the Iliac Crest. An Operative Approach with Decreased Morbidity

We compared the donor site morbidity in fifty-seven consecutive patients in whom a bone graft had been procured from the iliac crest through an incision parallel to the superior cluneal nerves and perpendicular to the posterior iliac crest (the study group) with that in fifty-three consecutive patients in whom the graft had been procured through an oblique incision parallel to the posterior iliac crest (the control group). Numbness, tenderness, and pain at the donor site one and six months postoperatively were assessed by means of an interview with the patient and a review of the records. The prevalence of symptoms in the control group was greater than that in the study group. At one month, thirty-nine patients (74 per cent) in the control group had numbness, compared with twenty-five (44 per cent) in the study group (p = 0.001). At six months, thirty-one patients (58 per cent) in the control group had numbness, compared with fourteen (25 per cent) in the study group (p = 0.0002). Thirty-six patients (68 per cent) in the control group and twenty-four (42 per cent) in the study group had tenderness over the incision at one month (p = 0.005), and twenty-seven (51 per cent) and eleven (19 per cent), respectively, had tenderness at six months (p = 0.0003). Forty patients (75 per cent) in the control group and forty-six patients (81 per cent) in the study group had deep pain in the region of the iliac crest at one month, compared with thirty-two (60 per cent) and thirty-one (54 per cent), respectively, at six months. The mean analog score for pain at the donor site was 7 of 10 points in the control group and 6 points in the study group (p = 0.001) at one month and 3 and 2 points, respectively, at six months (p = 0.001).

Properties of the stromal cell in giant cell tumor of bone.

The histiogenesis and mechanisms of bone destruction in giant cell tumor (GCT) of bone are not well understood. We asked whether the spindle-like stromal cells of GCT of bone exhibit osteoblastic properties, and whether the stromal cells produce active matrix-degrading proteases in vitro. We performed immunohistochemistry on 17 paraffin-embedded archival specimens with a pathologic diagnosis of GCT with monoclonal antibodies for the osteoblastic lineage markers osteopontin, osteonectin, and osteocalcin. The average staining grade for the 17 specimens was highest for osteonectin, followed by osteopontin, and osteocalcin. Primary cell cultures of GCT stromal cells were prepared from two fresh tumor specimens. Western blots were used on the cell lysates and media to detect osteocalcin precursor and the matrix-degrading proteases MMP-2 and MMP-9. We found the stromal cells in culture produce osteocalcin precursor, indicating osteoblastic lineage. The cells also express both the active and inactive isoforms of MMP-2 and MMP-9. Gelatinase assays confirmed the activity of the proteases in vitro. The spindle like stromal cells of GCT have characteristics of osteoblast progenitors and produce active matrix-degrading proteases. These cells may therefore play a central role in bone destruction.

The use of free vascularized fibular grafts in skeletal reconstruction for bone tumors in children.

Abstract The reconstruction of large skeletal defects in children following resection of a bone tumor presents a unique challenge to the orthopaedic surgeon. Issues in this population that are not present in the adult population include significant remaining growth potential, the desire for biologic preservation of the joint surface, and the need for a long‐term viable reconstruction in patients who are anticipated to survive for decades. The use of a free vascularized fibular graft, supplied by the peroneal vessels in intercalary fibular grafts and the anterior tibial vessels in proximal fibular grafts, has been shown to provide biologic reconstruction that successfully addresses these issues in the pediatric population. Specific techniques are applied in the upper and lower extremity to provide long‐term excellent functional results. Experience in microvascular surgery and careful postoperative care are required for the success of these procedures.

Upregulation of MMP-13 via Runx2 in the stromal cell of Giant Cell Tumor of Bone

Giant Cell Tumor of bone (GCT) is an aggressively osteolytic and cytokine-rich bone tumor. Previous work in our lab has shown that matrix metalloproteinase-13 (MMP-13) is the principal proteinase expressed by the mesenchymal stromal cells of GCT. The Runx2 transcription factor is known to have a binding site in the MMP-13 promoter region, and we have previously found this transcription factor to be constitutively expressed in GCT stromal cells. The purpose of this study was to determine the role of Runx2 in MMP-13 regulation in GCT stromal cells. Following in vitro stimulation of GCT stromal cells with incremental concentrations of cytokine IL-1beta or TNF-alpha, the level of MMP-13 mRNA expression increased dramatically over 100-fold with a concomitant increase in MMP-13 protein expression. Inhibition of the ERK and JNK signaling pathways inhibited the upregulation of MMP-13 in these cells. Runx2 siRNA knockdown resulted in MMP-13 knockdown, and this effect was amplified following cytokine stimulation. Our study provides the first evidence that Runx2 may play a crucial role in cytokine-mediated MMP-13 expression in GCT stromal cells.

Outcomes of an anatomically based approach to metastatic disease of the acetabulum.

Metastatic disease of the acetabulum is a common and challenging surgical problem. We asked whether acetabular reconstruction for metastatic bone disease improves functional outcome with an acceptable risk of surgical morbidity. We also asked if primary tumor type and the presence of visceral metastases predicted patient survival. We analyzed prospectively accumulated records of 62 consecutive patients who underwent 63 hip arthroplasties with acetabular reconstruction. Operative technique was guided by the extent of dome and column involvement. Demographics, functional status in the form of the Eastern Cooperative Oncology Group (ECOG) score, and survival data were analyzed. Functional scores improved from an average of 2.6 preoperatively to 1.1 postoperatively. Four patients had postoperative complications for which we performed further surgery. Mean survival for the patients with breast cancer was longer at 21 months compared to 9 months for the patients with other primary malignancies. Patients who did not present with visceral metastases had longer survival than those with visceral metastases. Despite the moderate risk of operative complications, an anatomically based approach to reconstruction of acetabular defects from metastatic disease improves functional outcome. Breast cancer as the primary malignancy and the absence of visceral metastases predicted longer survival.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Matrix Metalloproteinase Activity in the Stromal Cell of Giant Cell Tumor of Bone

Giant cell tumor of bone (GCT) is a destructive and potentially metastatic bone tumour in which the characteristic giant cells have classically been considered the culprits in bone destruction. However, the neoplastic element of the tumour consists of propagative osteoblast-like stromal cells that may play a role in bone resorption. The objectives of this study were to determine the expression and activity of the gelatinases, matrix metalloproteinase (MMP)-2 and -9, in GCT stromal cells, and to determine if these cells have bone-resorbing capabilities. We performed immunohistochemistry on clinical specimens, and real-time polymerase chain reaction (PCR) and zymography on cell lysates and conditioned media from cultured clinical GCT specimens in order to evaluate the expression and activity of MMP-2 and-9 in GCT stromal cells. Our results support the fact that GCT stromal cells express MMP-2 and MMP-9 and are capable of gelatin degradation in vitro. These cells may therefore play a role in bone destruction in GCT.

A Novel Surgical Approach to Lipomatous Tumours of the Deltoid Region

Resection of large lipomatous tumours in the subdeltoid region remains technically challenging due to the risk of injury to the axillary neurovascular bundle. We describe a novel deltoid release and reinsertion technique for resection of large lipomatous tumours of the sub-deltoid region and report the functional and oncologic outcomes of six patients who underwent this procedure. Three cases were diagnosed histologically as atypical lipoma and three cases were diagnosed as lipoma. There was one local recurrence in a case of an atypical lipoma. Rotator cuff function was comparable to that of the contralateral side in all cases and the average Constant Score adopted by the European Shoulder and Elbow Society was 84 (range 81 to 92) out of 100. We conclude that patients with large sub-deltoid lipomatous tumours who undergo resection through a previously undescribed deltoid release and reinsertion technique have excellent functional outcome with a low risk for recurrence.

Effect of Bone Morphogenetic Protein-2 and Doxycycline on the Differentiation of Osteoprogenitors from Human Femoral Bone

The purpose of this investigation was to evaluate the effects of bone morphogenetic protein-2 (BMP-2) and doxycycline on the in vitro differentiation of osteoprogenitor cells isolated from human femoral cancellous bone. The differentiation of osteoprogenitors into bone-forming osteoblasts was evaluated by alkaline phosphatase activity, osteocalcin gene expression, and the number of Von Kossa-positive bone nodules. Treatment of osteoprogenitors with BMP-2, at all concentrations tested, and doxycycline, at 10 and 50 � M, significantly increased the number of mineralized bone nodules and coincided with expression of osteocalcin. In conclusion, doxycycline at 10 and 50 �M had similar stimulatory osteoinductive effects as BMP-2 and could thus be considered as an alternative agent to BMP-2.