Dante Dallari

Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells.

BACKGROUND There is great interest in the use of bone substitutes to improve bone repair. We compared the osteogenic potential of lyophilized bone chips combined with platelet gel, or with platelet gel and bone marrow stromal cells, with that of lyophilized bone chips alone in the healing of a high tibial osteotomy. METHODS A prospective, randomized, controlled study was performed, and a standardized clinical model was applied. Thirty-three patients undergoing high tibial osteotomy to treat genu varum were enrolled and assigned to three groups. During the osteotomy, lyophilized bone chips with platelet gel were implanted into eleven patients (Group A), lyophilized bone chips with platelet gel and bone marrow stromal cells were implanted in twelve patients (Group B), and lyophilized bone chips without gel were placed in ten patients as controls (Group C). Six weeks after surgery, computed tomography-guided biopsies of the grafted areas were performed and the specimens were analyzed by histomorphometry. Clinical and radiographic evaluation was performed at six weeks, twelve weeks, six months, and one year after surgery. RESULTS Histomorphometry at six weeks showed significantly increased osteoblasts and osteoid areas in both Group A (p = 0.006 and p = 0.03, respectively) and Group B (p = 0.009 and p = 0.001) in comparison with controls, as well as increased bone apposition on the chips (p = 0.007 and p = 0.001, respectively), which was greater in Group B than in Group A (p < 0.05). Group B showed significantly higher revascularization than the controls (p = 0.004). Radiographs revealed a significantly higher rate of osseointegration in Groups A and B than in the controls at six weeks (p < 0.005 and p < 0.0001, respectively). At the final evaluation at one year, the osseointegration was still better in Groups A and B than in Group C; however, all patients had complete clinical and functional evidence of healing. CONCLUSIONS Adding a platelet gel or a platelet gel combined with bone marrow stromal cells to lyophilized bone chips increases the osteogenetic potential of the lyophilized bone chips and may be a useful tool in the treatment of patients with massive bone loss.

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses

Our aim was to determine if the serum levels of bone-resorbing cytokines (IL-1beta, TNF-alpha, IL-6, GM-CSF) are altered in patients with aseptic loosening of a total hip prosthesis, and if such levels are influenced by the type of implant. We determined cytokine levels in sera from 35 patients before revision for failed total hip arthroplasty and compared them with those in 25 healthy donors. We also assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication of a specific immune reaction against the implant. Our findings showed that the sIL-2r and TNF-alpha serum level did not change. The IL-6 level was not significantly altered, but was higher in patients with TiAIV prostheses than in those with a CrCoMo implant and in patients with cemented prostheses. The IL-1beta level was found to be higher in those with a TiAIV cemented prosthesis than in the control group (p=0.0001) and other groups of patients (p=0.003 v uncemented TiAIV, p=0.01 v cemented CrCoMo, p=0.001 v uncemented CrCoMo). The GM-CSF level significantly increased in patients compared with healthy subjects (p=0.008), and it was higher in those with cemented than with uncemented implants (p=0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF similar to those of the control group. The highest GM-CSF concentrations were observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) in the last months before revision (p=0.04). In addition, when massive osteolysis was observed, the level of GM-CSF tended to decrease to that of the control group.

Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study.

Adjuvant chemotherapy comprising Adriamycin (ADM) and Methotrexate (MTX) with Citrovorum Factor (CF) was administered on a randomization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor. One group received high dose MTX (regimen I) and the other moderate dose MTX (regimen II). In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery. All patients were free of metastasis at the beginning of therapy. The efficacy of therapy was determined by recording the percentage of continuously disease-free patients. This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only. The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group. Over the ensuing 27-66 months, 31 of 56 patients (55%) treated with regimen I and 25 of 50 (50%) treated with regimen II were disease-free. The overall disease-free survival in both regimens was 53%. This is similar to the 132 patients treated with previous adjuvant chemotherapy protocols (45-50%). However, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients (12%) treated contemporaneously with surgery only (P less than 0.0005). Survival in the latter is similar to that of historical control patients. These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy. These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious.

Metastatic patterns in osteosarcoma

The clinical courses of 193 patients with high-grade, non-metastatic osteosarcoma were reviewed to ascertain the evolution of the natural history of the disease. All patients had the primary lesion in the extremities and were treated at the Rizzoli Orthopaedic Institute between 1976 and 1982 with surgery alone (30 cases) or surgery plus adjuvant chemotherapy (163 cases). All patients were regularly followed at our Institute. One hundred and fourteen patients, of which 27 were treated with surgery alone and 87 treated with adjuvant chemotherapy, developed overt metastatic disease. No differences were found concerning the sites of the first relapse which, for approximately 90 % of cases, were lungs in both groups. However, in the group of patients treated with adjuvant chemotherapy the development of overt metastatic disease, as compared to non-adjuvant patients, was delayed with time (13 vs 8 months) and the number of metastatic nodules in the lung at first relapse was reduced. This alteration in metastatic pattern due to adjuvant chemotherapy is important because it allows surgical resection of pulmonary metastases in a larger number of patients (51 % vs 29 %).

Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study.

Background: The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in knee chondroplasty and osteoarthritis (OA); however, little evidence of its efficacy in hip OA exists. Purpose: To compare the therapeutic efficacy of autologous PRP, hyaluronic acid (HA), or a combination of both (PRP+HA) in hip OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients aged between 18 and 65 years who were treated with outpatient surgery and who had hip OA and pain intensity at baseline of >20 on a 100-mm visual analog scale (VAS) were recruited for this study. Exclusion criteria were extensive surgery; presence of excessive deformities; or rheumatic, infective, cardiovascular, or immune system disorders. The primary outcome measure was a change in pain intensity as assessed by the VAS at 2, 6, and 12 months after treatment. Secondary outcome measures were the Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and concentration of growth factors in PRP and their correlation with clinical outcomes. Clinical outcomes were evaluated by assessors and collectors blinded to the type of treatment administered. Results: A total of 111 patients were randomly assigned to 3 groups and received 3 weekly injections of either PRP (44 patients), PRP+HA (31 patients), or HA (36 patients). At all follow-ups, the PRP group had the lowest VAS scores. In particular, at 6-month follow-up, the mean VAS score was 21 (95% CI, 15-28) in the PRP group, 35 (95% CI, 26-45) in the PRP+HA group, and 44 (95% CI, 36-52) in the HA group (P < .0005 [PRP vs HA] and P = .007 [PRP vs PRP+HA]; F = 0.663). The WOMAC score of the PRP group was significantly better at 2-month follow-up (mean, 73; 95% CI, 68-78) and 6-month follow-up (mean, 72; 95% CI, 67-76) but not at 12-month follow-up. A significant, “moderate” correlation was found between interleukin-10 and variations of the VAS score (r = 0.392; P = .040). Significant improvements were achieved in reducing pain and ameliorating quality of life and functional recovery. Conclusion: Results indicated that intra-articular PRP injections offer a significant clinical improvement in patients with hip OA without relevant side effects. The benefit was significantly more stable up to 12 months as compared with the other tested treatments. The addition of PRP+HA did not lead to a significant improvement in pain symptoms.

A prospective, randomised, controlled trial using a Mg-hydroxyapatite - demineralized bone matrix nanocomposite in tibial osteotomy.

We in vivo investigated the bone healing ability of a nanocomposite (DBSint®), constituted by biomimetic nano-structured Mg-hydroxyapatite (SINTlife®) and human demineralized bone matrix. Thirty-one subjects undergoing high tibial osteotomy for genu varus were randomly assigned to three groups: during surgery, DBSint® was inserted into nine patients, SINTlife® in thirteen patients and lyophilised bone chips, that is the routine surgery, in nine subjects. As outcome measures, clinical, radiographic and histomorphometry scores were calculated. The osseointegration was evaluated by imaging six weeks, three, six and twelve months after surgery. At six-week follow-up, DBSint® showed a significantly higher osseointegration rate in comparison with lyophilised bone chips (p = 0.008). At the same follow-up, CT-guided bone biopsies were obtained and analysed by histomorphometry: a good osteogenetic potential was demonstrated with DBSint®, as well as with SINTlife® and controls. Unresorbed material was evident with DBSint® and SINTlife®, with a significantly higher percentage in SINTlife® group. At 1-year follow-up, DBSint® was demonstrated as effective and safe as SINTlife® and lyophilized bone chips. More significant results could be obtained by continuing the clinical trial, by increasing the patient number and the study power. Eventually, the role of non-resorbed graft remnants is still unclear and requires further investigation.

Prognostic value of serum alkaline phosphatase in osteosarcoma.

In 163 patients with osteosarcoma of the extremities treated with adjuvant chemotherapy, serum alkaline phosphatase (SAP) levels were evaluated before treatment and successively closely monitored in an attempt to determine whether serum levels of this enzyme had clinical value in predicting the course of the disease. Of 121 patients with elevated preoperative SAP levels, 78 (64%) recurred. Of 42 patients with normal preoperative SAP levels, only 8 (19%) recurred (P < 0.00001). Of the 140 patients locally treated with amputation, SAP returned to normal values in 77 patients; 46 of these (59%) relapsed. Of the 21 patients whose SAP remained elevated after amputation, all but 2 relapsed (90%). Among 119 patients with normal postoperative values of SAP, at the time of relapse SAP resulted elevated in 22 of 41 patients (53%). These data confirm that in osteosarcoma, preoperative SAP levels have a definite value in establishing the prognosis and that posttreatment follow-up examination should include SAP determination, since persistent elevated or increasing values herald the appearance of a recurrence.

Two Stage Hip Revision in Periprosthetic Infection: Results of 41 Cases

Background: two-stage revision is considered the best treatment approach for the eradication of chronic joint infection. We report the outcome of 41 consecutive patients with infected hip prostheses, treated between 2000 and 2005, with two-stage revision using an antibiotic-loaded cement spacer. Methods: Patients underwent a treatment protocol which included clinical and radiographic evaluation, laboratory investigations, hip aspiration, 99mTc-MDP and 99mTc-leukocyte-labeled scintigraphy and intraoperative assessment. All patients were diagnosed with a late chronic infection and classified as B-host according to the Cierny-Mader classification system. 9 patients out of 41 (22%) required a second interim treatment period, with exchange of the spacer. The proportion of methicillin-resistant Staphylococcus was similar between the one-spacer group and two-spacer group (28% vs 33%), whereas the proportion of patients with three or more risk factors was significantly higher in the two-spacer group than in the one-spacer group (28% vs 55%, respectively). Results: Forty patients had final reimplantation, one patient had a resection arthroplasty. At an average follow-up of 5.3 years no recurrence of infection occurred. The average post-operative Harris hip score improved from 41 to 80. Conclusions: In the treatment of two-stage revision arthroplasty the adherence to the protocol proved to be effective for infection eradication and final reimplantation.

Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity.

Between March 1983 and September 1988, 22 patients with non-metastatic malignant fibrous histiocytoma MFH of bone of the extremities were treated with two regimens of neoadjuvant chemotherapy successively activated. Preoperatively, the patients received moderate doses of methotrexate and cisplatinum-Regimen 1- or high dose methotrexate, cisplatinum and adriamycin-Regimen 2. Cisplatinum was delivered intra-arteriously, the other drugs intravenously. Limb salvage surgery was performed in 20 patients, and 2 patients were amputated. The surgical margins were adequate (radical or wide) in 18 cases and inadequate (marginal) in 4. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 8 patients. In both regimens postoperative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. At an average follow-up of 40 months (15-70), 15 patients (68%) remained continuously disease-free and 7 relapsed with metastases. No local recurrences were observed. Regimen 2 was slightly more effective than Regimen 1 in terms of good histologic response (5/10 vs 1/12) and continuous disease-free survival (8/10 vs 7/127). The results demonstrate that, as in osteosarcoma, in non-metastatic malignant fibrous histiocytoma of bone in the extremities a high percentage of patients can be cured with neoadjuvant chemotherapy and that in most of them limb sparing surgery is possible and safe.

Bilateral total hip arthroplasty in Morquio-Brailsford's syndrome: a report of two cases.

We report two cases of bilateral cementless total hip arthroplasty in two young women affected by Morquio-Brailsford syndrome. Morquio-Brailsford disease belongs to the mucopolysaccharidoses; it shows growth retardation with disproportional dwarfism. Usually patients are affected by a severe joint degeneration from their 2nd or 3rd decade. Young age, severe dysplasia, and joint size are the main technical problems for a total hip replacement. Accurate radiographic and CT planning allows the use of standard prostheses instead of custom-made ones.