A Comparison of Mineral Bone Graft Substitutes for Bone Defects
healed, mean Musculoskeletal Tumor Society (MSTS) scores were 98% of normal, and one out of 24 patients (4.2%) sustained a post-operative pathologic fracture.33
The same authors in an improved version of the
same study with greater numbers (98) and longer follow-up (mean 32 months) noted 100% resorption with bone formation by six months in all cases and a 3.1% post-operative pathologic fracture rate.34
In another
study, the authors looked specifically at benign bone tumors curettaged and then grafted with an injectable form of calcium sulfate (MIIG 115) in a liquid vehicle. Fourteen out of 15 (93.3%) of the grafted defects showed complete radiographic incorporation of the graft material at an average of eight weeks. There was one (0.7%) deep infection and one (0.7%) pathologic femoral neck fracture.35
A retrospective review of 28 children
with UBCs in different sites treated with a percutaneous aspiration, curettage, and Osteoset pellet injection grafting technique resulted in two (7.1%) persistent cysts, one of which required further surgery.36
In a
continuation of this study, the authors retrospectively reviewed 27 more (55 total) pediatric UBCs. They found that 11 required at least one more surgery for recurrence, with two of 55 (3.6%) developing superficial drainage that was successfully treated with oral antibiotics alone and three of 55 (5.5%) sustaining post-operative fracture.37
One review of 58 Osteoset-grafting cases in the treatment of benign bone tumors noted a 13.8–19.0% rate of ‘adverse reaction’ to the graft, which consisted of erythema, edema, and serous drainage.39
In a
subsequent article, the same journal published a series of 22 children with UBCs treated with aspiration and injection of liquid calcium sulfate (MIIG 115) or liquid calcium sulfate plus calcium phosphate hybrid (Prodense).40 They noted three cases of laryngospasm immediately after injection (all treated with MIIG), two of which required intubation and all of which resolved without further complication. They also noted one case of temporary systemic venous thrombosis (SVT) immediately after injection with Prodense, which resolved without complications.
Kelly et al. conducted a level II prospective, multicenter cohort study of Osteoset pellets in 109 patients requiring a morcelized bone graft for a non-structural bone defect from multiple conditions in multiple locations (including a 46-patient subgroup of benign bone tumors). Of these, 65% had adjuvant graft (DBM, bone marrow aspirate, cancellous allograft, or cancellous autograft).42
Of all studies regarding the use of calcium sulfate in benign bone defects, only two high-level clinical studies (level I/II) have been performed.41
Other studies have noted some downsides to calcium sulfate as a bone graft. One series of 15 cases of Osteoset pellet grafting following benign bone tumor resection revealed three cases of severe inflammatory reaction, one of which resolved two months post-operatively. One reaction resulted in wound dehiscence and one required surgical graft debridement. These results caused the authors to conclude that “due to rapid graft resorption, the resulting calcium-rich fluid incites inflammation.”38
created after bone–patellar-tendon–bone harvest for knee ligament surgery. The authors studied the amount of new bone formation with serial computed tomography (CT) scans at 0, 6, 12, and 24 weeks.43 Significantly increased new bone was found in both groups from zero to six weeks and significantly increased bone was observed in the control group alone from six to 12 weeks compared with Osteoset (p=0.01). However, no statistical difference was found between the two groups at any time interval.
Calcium Phosphates Hydroxyapatite
In response to the rapid absorption and inflammation associated with calcium sulfate, calcium phosphate compounds with potentially improved biological and mechanical properties gained popularity. In the
calcium phosphate family, hydroxyapatite (HA: Ca10(PO4)6(OH)2) is derived from the sea corals Porites and Goniopora. It is created by a hydrothermal exchange that converts calcium carbonate in the coral exoskeleton to crystalline HA.4,20
human trabecular bone and it is available in blocks, granules, or cement formulations. HA has compressive strength but remains brittle, with low tensile strength.15,44
Another canine model found the HA graft site to consist of 52% soft tissue, 13% new bone, and 35% HA at 12 months, with 67% of the HA surface being covered with new bone.46
In a canine humeral
defect model, at 16 weeks 50–60% of pores were filled with new bone and compressive strength was two to three times that of the surrounding cancellous bone; however, the grafted area only reached cortical bone strength, and the bending strength of the associated cortical bone returned to only 10% of its normal value.47
Shors and Holmes looked at 37
biopsy specimens of HA implants taken a mean 14 months post-grafting through light microscopy and electron scanning microscopy. They found 30% soft tissue, 31% HA, and 38% new bone, with 56% of the implant surfaces being covered by bone.48
All of the clinical studies using HA grafting in the treatment of bone tumors are retrospective in nature (see Table 2). One study looked at 23 patients in whom simple bone cysts were treated by curettage followed by HA cube packing. It found complete healing without cyst recurrence in 78% of cases at two years, with new bone surrounding the HA at an average of 2.3 months.49
Two Indian studies of bovine HA studied grafting Looking at calcium
sulfate alone, there was 99% resorption and 98% new bone formation at 12 months. In the bone tumor subset treated with Osteoset alone (10 patients), there was 100% graft resorption and 97% new bone formation at 12 months. There was a 12% complication rate, including three infections (2.8%), two pathologic fractures (1.8%), and four cases of serous drainage that resolved once the pellets were absorbed (3.6%). An elegant level 1 prospective randomized, double-blind, controlled study compared calcium sulfate versus no grafting at all in tibial bone defects
US ONCOLOGY & HEMATOLOGY
after benign bone tumor treatment in a small number of cases (12 and 23) and followed them clinically and radiographically for up to six years. The authors found the graft material to be biocompatible, safe, and slow to remodel, with no adverse effects or graft-related complications.50,51 Uchida et al. reported on 60 cases in which HA bone graft was used to fill resected benign bone tumors. Patients were followed up for a mean of 36 months.52
The authors biopsied seven specimens (cases requiring surgery for other reasons) and found new bone ingrowth onto the graft in all cases. They did, however, experience three (5%) pathologic fractures and saw minimal radiographic resorption in all cases, even at five years. Another study looked retrospectively at 51 patients with
41
Several pre-clinical studies have evaluated the initial safety and efficacy of HA as a bone void filler. In their implantation of 52 canine bone defects from various sites with HA, the authors of one study found the construct to be weak initially, but to be almost as strong as native bone upon incorporation.45
Its 200–500µ pore size is similar to
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