Abstract
Background: A new β-tricalcium phosphate with uniform triple superpore structure, SuperPore® (HOYA, Tokyo, Japan), has been in clinical use since 2010. As far as we are aware of, there have been no reported clinical studies using this material. We report on the first clinical cases of benign bone tumor filled with SuperPore®. Patients and Methods: We retrospectively evaluated the results for 34 benign bone tumors treated by curettage followed by implantation of the highly purified β-tricalcium phosphates Osferion® (Olympus, Tokyo, Japan) or SuperPore®. Results: After a mean follow-up of 12 months, none of the patients experienced local recurrence of the tumor or any adverse effects from the filling materials. Radiographically, complete resorption of the material and bone remodeling were achieved in 32 cases. In 17 selected cases with a small bone tumor, the mean period for complete resorption of the filling material was 21 weeks in the Osferion® group and 15 weeks in the SuperPore® group, with the latter showing a trend for better outcomes. Conclusion: SuperPore® is a safe and reliable filling substitute for defects following curettage of small bone tumors. Both SuperPore® and Osferion® gave satisfactory results with good biocompatibility and fast resorption characteristics.
A variety of synthetic bone grafts have been used to fill cavities following curettage of bone tumors. Hydroxyapatite had been widely used as a bone graft substitute because it has a high compressive mechanical strength and good osteoconductivity. More recently, highly purified β-tricalcium phosphate (β-TCP) has been commonly used in place of hydroxyapatite because it is osteoconductive and also biodegradable.
The highly purified β-TCP Osferion® (Olympus, Tokyo, Japan) has been used since 1999 (1-6). Starting in 2010, a new superporous β-TCP with a uniform triple pore structure, SuperPore® (HOYA, Tokyo, Japan), has been introduced in the clinical setting. Although several animal experiments demonstrated satisfactory biocompatibility of SuperPore®, as far as we aware of there, have so been no clinical reports using this filler.
In the present study, we evaluated the efficacy of SuperPore® as a bone graft substitute to fill the defect left after curettage of benign bone tumors, as well as comparing it to Osferion®.
Materials and Methods
β-TCP and patients. This study was a retrospective, uncontrolled review of 34 consecutive patients with benign bone tumors of the extremity treated by curettage and followed by implantation of highly purified β-TCP.
From 2005 to 2011, the granular type of Osferion® (porosity of 75%, granular size of 2 mm) was used for 16 patients (Table I). This group comprised eight men and eight women with a mean patient age of 40 (range=10 to 76) years and average follow-up time of 48 (range=15 to 100) weeks. Starting in 2011, granular SuperPore® (porosity of 75%, granular size of 2 mm) was used for 18 patients (Table II). This group comprised nine men and nine women with a mean age of 36.2 (range=10 to 82) years and average follow-up time of 51 (range=14 to 103) weeks. The histological diagnoses for the overall cohort were 15 cases of enchondroma, four aneurysmal bone cysts, four solitary bone cysts, three intraosseous ganglions, three fibrous dysplasias, three non-ossifying fibromas, one eosinophilic granuloma and one intraosseous lipoma.
Surgical procedure. The tumor was exposed through an appropriately-sized bone window. After curettage of the tumor, the defect was filled with purified granular β-TCP. This was implanted gently into the cavity so as not to break the porotic structure. Cryosurgery was performed after curettage in two patients with aneurysmal bone cyst. Postoperatively, the affected extremity was not immobilized with a splint.
Summary of the patients treated with Osferion®.
Summary of the patients treated with SuperPore®.
Evaluation. Evaluation in all cases was based on clinical examination at the final follow-up and serial radiography. The filler volume of β-TCP was calculated according to the method proposed by Anker et al. using the antero-posterior, transverse and cephalocaudal dimensions on a radiograph (7). Resorption and remodeling of β-TCP were assessed by the method proposed by Nicholas and Lange (8). The period of complete resorption or remodeling of β-TCP was diagnosed by radiological findings showing loss of granular pattern and trabecular bone formation. Because of the significant size differences between upper and lower limb tumors, 17 cases with small tumors in the hands and fingers were selected for further study. Of these, 11 were treated with Osferion® and six with SuperPore®. The Osferion® group included four males and seven females, with an average age of 45 years and an average follow-up of 43 weeks. The SuperPore® group included three males and three females, with an average age of 31.3 years and an average follow-up of 34 weeks.
Comparison of Osferion® and SuperPore® in cases with small bone tumor of the hand.
Comparison of SuperPore® and Osferion®.
Statistical analysis. An unpaired t-test was used to compare differences in age, follow-up time, filler volume with β-TCP, time to pain relief and bone remodeling time between groups. A p-value less than 0.05 was considered to be significant. All analyses were performed using Graphpad Prism version 6.01 (GraphPad Software, San Diego, CA, USA).
Results
Clinical outcome. No serious complications directly related to the bone substitution were noted, including infection, allergic reaction, fracture or tumor recurrence. The period of pain relief averaged at 15.4 weeks postoperatively in the Osferion® group and 18.5 weeks in the SuperPore® group, with no significant differences between the two.
Resorption of β-TCP. Radiographically, the mean filler volume of β-TCP immediately after operation was 4.8 cm3 in the Osferion® group and 14.5 cm3 in the SuperPore® group. Six out of the 18 cases in the SuperPore® group had relatively large bone tumors in the humerus or tibia and hence the volume used was higher than that used in the Osferion® group. Complete resorption of β-TCP and bone remodeling was observed in all Osferion® cases, with an average time of 22 weeks, as well as in 16 SuperPore® cases (89%), with an average time of 21 weeks.
During the course of remodeling, 26 cases showed no radiolucent rim surrounding the β-TCP, with a uniform pattern of β-TCP resorption and trabecular bone formation (Figure 1a-c). Six cases showed a radiolucent rim, but with uniform resorption and trabeculation. The two remaining cases (#10 and 28) showed a radiolucent rim with the remodeling starting peripherally and progressing centrally (Figure 2a-c).
In 17 selected cases with small bone tumors, the SuperPore® group had a trend for better outcome; however, the difference from the Osferion® group did not reach significance. The mean period to pain relief was 14 weeks in the Osferion® group and 9.5 weeks in the SuperPore® group (p=0.23) (Figure 3a-c). The mean period for complete resorption of the β-TCP filler was 21 weeks in the Osferion® group and 15 weeks in the SuperPore® group (p=0.40; Table III).
Discussion
SuperPore® versus Osferion® regarding porous structure. SuperPore® is a newly developed superporous β-TCP. This study was conducted to compare two types of highly purified β-TCP, SuperPore® and Osferion®. These β-TCPs are different in terms of fabrication and structure. Generally, macropores in β-TCP with a diameter of >100 μm provide a scaffold for bone-cell colonization. Micropores (diameter <1 μm) on the other hand allow circulation of body fluids and may provide an environment for collagen formation, thus leading to the deposition of apatite crystals (9-15) (Table IV).
SuperPore® is manufactured by wet mixing and the spray-dry method, whereas Osferion® is made using a mechanochemical method. Under the scanning electron microscope, Osferion® has non-homogeneous macro- and micropores, whereas SuperPore® has uniform triple pore structures. The size of macropores and micropores is approximately 200 μm and 0.5 to 10 μm, respectively. Interestingly, interconnecting pores with a diameter of 50 to 100 μm are observed (Figure 4) (16). Bucholz et al. reported that the ideal pore configuration would have uniform size, uniform configuration and interconnecting fenestrations (9). This provides the theoretical advantage of better vascular and osseous in-growth compared to a random pore structure.
A 16-year-old man presented with pain in the left distal femur which was diagnosed as nonossifying fibroma (case 29). After curettage, the bone defect was filled with the granular type of SuperPore® (a). The postoperative radiograph at three months showed no radiolucent rim surrounding the β-TCP (b). The radiograph at nine months showed a uniform pattern of β-TCP resorption and trabecular bone formation (1c).
Remodeling of SuperPore®. Sakamoto et al. experimentally implanted SuperPore® in a canine femoral defect to investigate the remodeling properties of this material (16). At four weeks postoperatively, newly-formed bone was visible and the β-TCP had been resorbed. Interestingly, at 26 weeks, the β-TCPs implanted in the cortex remodeled into cortical bone, while β-TCPs implanted in the medullary remodeled into a medullary structure. To our knowledge, there have been no clinical reports on SuperPore® and hence the present cohort may represent the first reported cases.
The mechanism of bioceramic resorption involves two processes: solution-mediated processes and cell-mediated disintegration. In earlier studies, Anker et al. (7), Ogose et al. (11) and Nicholas and Lange (8) reported that resorption and trabeculation of implanted β-TCP occurred in a centripetal fashion. This was revealed on radiographs as a shrinking peripheral rim of radiolucency at the interface between the surrounding host bone and the central, less well-incorporated graft material. Ogose et al. investigated four cases involving grafted β-TCP in human bone with respect to histological features. They used routine hematoxylin and eosin staining, silver impregnation, immunohistochemistry and in situ hybridization to observe changes. The early phase involved vascular invasion of macropores. Osteoblasts and osteoclasts attached to the surface of macropores and massive collagen fibers were observed within the macropore 14 days after grafting. Bone formation 28 days after grafting was more prominent in the periphery of the grafted area than in the center. β-TCP was surrounded by lamellar bone and active osteoblastic cells and osteoclasts were not observed 72 days after grafting. Gaasbeek et al. performed bone biopsies from 16 patients treated with open wedge high tibial osteotomies using β-TCP (17). They reported more bone apposition in the pores closest to the osteotomy. The peripheral rim of radiolucency reflected peripheral dissolution of β-TCP.
In our study, only two cases (#10 and 28) exhibited remodeling that progressed in a centripetal fashion. Interestingly, the remodeling time for both these cases (49 weeks) was much longer than the average of 19 weeks for the remaining cases. Approximately 80% of patients did not exhibit a radiolucent rim surrounding the β-TCP and remodeling progressed uniformly in the transplanted material. The differences in these remodeling processes were likely to be due to: i) the use of a smaller particle size, granular form of β-TCP in our study that had a broader surface than the block type; ii) the inclusion of many small tumors (<2 cm) in our study; and iii) the porous structure being maintained without compression of β-TCP during implantation, if compressed, resorption and trabeculation may occur slowly and centripetally due to porous changes in the material.
Two patients (#31 and 34) exhibited residual β-TCP. The resorption of β-TCP may depend on the patient's age and the filler volume. Nicholas and Lange reported that healing was dependent on the defect size (8). Arai et al. used β-TCP to backfill the defect created by harvesting the fibula (4). β-TCP was replaced by newly-formed bone in all children, but only 1/11 adult patients experienced complete regeneration of the fibula. Our two cases #31 and 34 had large bone defects (37 and 44 cm3) and case 34 was 75 years old.
A 34-year-old woman presented with spontaneous pain of the calcaneus which was diagnosed as an interosseous lipoma (case 28). The bone defect was filled with SuperPore® (a). The postoperative radiograph at three months showed a radiolucent rim surrounding β-TCP (b) and that at nine months showed a radiolucent rim with the remodeling starting peripherally and progressing centrally (c).
In our series, both β-TCPs demonstrated excellent resorption and remodeling. The remodeling periods were not significantly different between the two β-TCP groups. Further investigations of larger cohorts, and including cases with larger tumors, may reveal significant differences in remodeling between different β-TCPs.
An 82-year-old man presented with a one-month history of pain in the right elbow joint (case 26). The radiographs showed a well-margined osteolytic lesion of 3.7×1.3×1.3 cm in the proximal radius (a). Intraosseous ganglion was diagnosed, the tumor was curetted through a bone window of 40×5 mm and the defect filled with SuperPore® (b). The postoperative course was uneventful and complete resorption and trabeculation were achieved three months after surgery (c).
Scanning electron microscope images of SuperPore®. The size of the macropores was from approximately 50 to 300 μm (a) (×50). Many interconnecting pores can be seen among the macropores and micropore gaps between secondary particles of TCP ceramics on the pore walls (b) (×500). The size of the interconnecting pores and micropores is from 50 to 100 μm and from 0.5 to 10 μm, respectively.
Strength of SuperPore®. Because of its structural properties, SuperPore® was proven to have a greater compressive strength compared to Osferion®. The compressive strength of SuprePore® with 75% porosity was 5 to 7 MPa, whereas that of Osferion® of the same porosity was 2 to 5 MPa.
Following the curettage of benign bone tumors, mechanical weakness may occur because a bone window is made in the cortical bone. High-intensity artificial bone has the advantage of being able to cover mechanical weakness. In our cases, the difference in strength of the β-TCPs did not affect the results because the cases were limited to small tumors. There could potentially be a difference, however, if β-TCPs are used for larger bone tumors, or for weight-bearing bone.
If the rate of β-TCP degradation is faster than the rate of bone formation, its mechanical strength could weaken and it would no longer be effective as a scaffold for bone formation. In our cases, the resorption of SuperPore® and the formation of new bone were well-balanced. The average period to the completion of remodeling was quite fast, being approximately 15 weeks in cases with small bone defects.
Attempts to enhance bone growth to β-TCP. Although β-TCPs give good results, they remain inferior to autogenous bone grafts. β-TCP has an osteoconductive effect because it allows bone in-growth from an osseous bed, but there is no evidence that it has an osteoinductive effect (9, 18). Future objectives are to accelerate bone growth and to enhance the compression strength (12, 15, 19-21).
Dimer et al. reported that β-TCP with recombinant human bone morphogenetic protein-2 and bovine type-1 collagen gave better results than autogenous iliac crest bone graft for lumbar spine arthrodesis (19). Orii et al. also reported that β-TCP grafts combined with bone marrow derived stromal cells led to better results than iliac bone graft (14). Further studies on the concomitant use of β-TCP with alendronate or human parathyroid hormone should prove worthwhile (20).
Conclusion
SuperPore® is a new superporous β-TCP with uniform triple pore structure that has been in clinical use since 2010. We have compared clinical results between SuperPore® and Osferion® for benign bone tumors. Both β-TCPs led to satisfactory results, with good biocompatibility and fast resorption characteristics. SuperPore® and Osferion® were both safe and reliable filling substitutes for defects after curettage of small bone tumors. SuperPore® may be more suitable for larger bone defects because of its greater compressive strength.
- Received August 28, 2013.
- Revision received September 26, 2013.
- Accepted September 30, 2013.
- Copyright© 2013 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
