Musculoskeletal Cancer
minutes, a final set time of 7.5 minutes at 37ºC, and a final compressive strength of 48MPa at 24 hours (the maximum compression strength of cancellous bone is 30MPa).77
A study of the calcium phosphate cement
Norian SRS showed a final compressive strength of 55MPa at 24 hours.78 This graft and surrounding bone remodels over time. It is absorbed by osteoclasts, results in new lamellar bone formation, and resorbs slowly, with 30–60% resorbed at one year.79
Most of the calcium phosphate
cements cure in an isothermic manner; however, some may be slightly exothermic (e.g. Mimix), albeit not enough to cause the thermal tissue damage seen with polymethylmethacrylate.79
A human cadaveric lateral
tibial plateau fracture model comparing cancellous grafting with α-BSM calcium phosphate bone cement found statistically increased stiffness and resistance to displacement (p<0.0001) in the α-BSM group.80
Progressing from these pre-clinical studies, numerous level I studies have prospectively looked at calcium phosphate cement (Norian and α-BSM) in the supportive treatment of metaphyseal fractures (see Table 3). These studies have found statistically improved early motion in distal radius fractures,81,82
extremity fractures,83–86
earlier weight-bearing and mobilization in lower improved maintenance of reduction,87–92
improved early fracture stability in hip fractures.87,88 and Interestingly, after
publishing a level I study in favor of Norian SRS in femoral neck fractures, Mattsson et al. in a subsequent study of femoral neck fractures found a statistically increased revision rate in the calcium phosphate cement group and did not recommend its use.85
This being said, the majority of
the data highly support the use of calcium phosphate cements for metaphyseal support in peri-articular fractures. No high-level human studies evaluating the use of calcium phosphate cements in the treatment of bone defects from tumor have been performed.
Mineral Bone Graft Composites
In the quest to improve the delivery vehicle of bone graft substitutes in order to avoid problems—including difficult handling, inability to fully fill the void, extravasation into soft tissues, and the desire to obtain further biological advantage—collagen- and silicon-based composites were developed. Modifications of the TCP include the formulation packing, strip, or moldable putty vehicles that usually involve the addition of a matrix substance such as type I bovine collagen (i.e. Vitoss Scaffold Foam).
The addition of type I collagen decreases compressive strength and the collagen portions are quickly absorbed.5
These composites cannot be
used in patients with allergies to bovine collagen. In a level I prospective, randomized, multicenter study, 297 long-bone fractures from various sites that required surgical stabilization were grafted with 65% HA/35% TCP plus type I bovine collagen (Collagraft) or iliac crest autograft. The authors were unable to find differences in union (88% power) or function between the groups. Twelve patients developed bovine collagen antibodies, but no related problems occurred.93
With regard to silicated mineral compounds, no studies have been performed to evaluate their safety and efficacy in human bone defects. In vitro biochemical studies have produced mixed results, with some claiming improved biological activity with silication by increasing the solubility of the material, creating a more electronegative surface, and developing a finer microstructure.94
A conflicting bench study states that “there is no experimental evidence that Si ions are released from 46
In addition to silicon or bovine collagen, celluloid polymers may act as plasticizers and potential biological inducers for mineral bone grafts. No studies of such compounds have been performed on human bone defects. Biphasic calcium phosphate ceramic particles were plasticized with the polymer hydroxypropylmethylcellulose (HPMC) and then implanted into rabbit femoral defects.97
At eight weeks, the yield
strength for the grafted group was significantly higher than for the host trabecular bone tissue. Histology revealed that osteoconduction had occurred. In a canine humerus model comparing calcium sulfate paste (MIIG 115) mixed with HPMC versus MIIG 115 alone, the added HPMC enabled better handling. There was similar progressive resorption and new bone formation on X-ray, and the area of new bone, residual implant, and strength were similar between the two groups.98
In order to obtain the optimal chemical and biological characteristics of the available mineral compounds (i.e. resorption profiles), mixtures of the mineral compounds themselves were developed. In a canine study of diaphyseal fracture defects filled with a granular HA/TCP ceramic, the authors concluded the graft was biocompatible and osteoconductive but not osteoinductive or osteogenic, being unable to promote healing in large fracture defects.99
A combination of 75% calcium sulfate plus
25% calcium phosphate (brushite plus β-TCP) injectable cement called Prodense is now available. In a canine humeral defect model, calcium sulfate pellets (Osteoset) were compared with Prodense. The authors found statistically increased ultimate compressive strength in the Prodense group compared with both Osteoset and normal trabelcular bone at all time intervals.100
The Prodense group also had an elastic
modulus statistically closer to bone than Osteoset. They noted that Prodense was resorbed at a statistically slower rate than Osteoset and that there was residual Prodense in all samples at 26 weeks. A review of 13 patients who underwent treatment of aggressive benign bone tumors (aneurysmal bone cysts and giant cell tumors) with grafting with composite 65% HA/35% calcium sulfate found a mean time to consolidation of 18 weeks (range 12–28 weeks). There were two (15.4%) local recurrences, one post-operative fracture (7.7%), and no graft-related complications.101
A retrospective review of 75 patients who US ONCOLOGY & HEMATOLOGY
Si-substituted calcium phosphates at therapeutic concentrations, and there is no study linking the improved biological performance of Si-substituted calcium phosphates to Si release.”95
In an elegant animal
histological study, the authors compared calcium sulfate (Osteoset), ultraporous β-TCP (Vitoss), and silicated calcium phosphate (Actifuse) in the grafting of osteochondral defects in the subchondral bone of the femoral condyle of rabbits. The authors compared the response according to histologic parameters from one to 12 weeks.96
They noted
rapid resorption of calcium sulfate, which elicited an inflammatory response and left the defect site empty before significant quantities of new bone were formed. Both β-TCP and Si-CaP scaffolds supported early bone apposition. They found, however, that β-TCP degradation products provoked an inflammatory response that impaired and reversed bone apposition. They stated that the rapid graft resorption of β-TCP impaired new bone growth through dissolution of the scaffolding and through inflammation-related retardation. They concluded that Si-CaP appeared to provide a more stable osteoconductive scaffold and supported faster angiogenesis and bone apposition compared with calcium sulfate and β-TCP.
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