Clinical Efficacy of Platelet-Rich Plasma on Allograft Transplantation after Core Decompression for Osteonecrosis of the Femoral Head

Introduction

Complete treatment of osteonecrosis of the femoral head remains an unsolved issue in orthopedic surgery. Many treatments that involve articular preservation have been introduced; however, the best treatment has not yet been established. Most patients who undergo non- operative treatments eventually require hip joint transposition owing to post-operative progression to early femoral head depression and articular dissonance [1]. Core decompression, an articular salvage operation, is used most frequently due to its simplicity and superior outcomes [2]. Core decompression treats the initial non- traumatic femoral head osteonecrosis, and many authors have hypothesized that restoration of femoral head circulation induced by facilitated venous flow in the bone marrow and decreased internal pressure of the femoral head leads to osteogenesis [3]. Recently, the post core decompressive track has been used for bone transplantation due to the expected effects of bone transplantation on adaptation to weight loading [4]. Through a review of previous papers [1] that reported no difference in success rate between decalcified bone matrix transplantation and autologous bone graft performed simultaneously with core decompression, we concluded that the issue of donor area could be resolved. Further, administration of platelet-rich plasma enables the heavy discharge of highly concentrated platelet- derived growth factor (PDGF), transforming growth factor-β (TGF-β), and insulin-like growth factor-1 (IGF- 1),[5] suggesting that platelet-rich plasma infusion could promote simultaneous bone cell differentiation and proliferation with unlimited allogeneic bone transplantation and could greatly improve the post- operative outcomes of bone transplantation through core decompression. Hence, in this retrospective study, we compared the outcomes of post-operative allogeneic bone transplantation performed with and without the administration of platelet-rich plasma after core decompression to treat femoral head osteonecrosis. We evaluated the following outcomes: rate of successful operation by Ficat-Arlet and ARCO staging, percentage of necrotic area on the MRI image, pain alleviation on a visual analogue scale (VAS), and mobility by the Harris Hip Score.

Simple radiographs and MRI images were used to determine the pre-operative radiographic Ficat-Arlet and ARCO stages. The percentage of necrotic area to the entire area of the femoral head on the midsagittal section of the MRI image was measured with graph paper (Figure 1,2,3); these measurements were categorized as follows: group A, up to 25% necrotic area; group B, 26% to 50% necrotic area; group C, 51% to 75% necrotic area; and group D, over 75% necrotic area. The MRI images (T1-weighted spin-echo image [TR = 686.0 msec, TE = 10.3 msec] and T2-weighted spin-echo images [TR = 4577.0 msec, TE = 75.3 msec]) of the coronal and sagittal views of the hip joint around the center of the femoral head were obtained with 2 mm of thickness and spacing using the DISCOVERY MR750w (GE Healthcare, America).

Results

The pre-operative radiographic classification according to the Ficat-Arlet stage revealed that the group that received the platelet-rich plasma with the allogeneic bone graft included 4 cases of Stage I, 10 cases of Stage IIA, and 6 cases of Stage IIB. Success rates were 100% (4 cases) for Stage I, 60% (6 cases) for Stage IIA, and 0% (0 cases) for Stage IIB. The group that underwent the operation without platelet-rich plasma included 5 cases of Stage I, 11 cases of Stage IIA, and 4 cases of Stage IIB. Success rates were 80% (4 cases) for Stage I, 36.4% (4 cases) for Stage IIA, and 0% (0 cases) for Stage IIB. For each group, the lower stages were associated with higher rates of success (p=0.01, p=0.02, respectively; Tables 1, 2).

Pre-operative radiographic classification with ARCO staging revealed that the platelet-rich plasma group included 2 cases of Stage I, 12 cases of Stage II, and 6 cases of Stage III, with associated success rates of 100% (2 cases), 66.6% (8 cases), and 0% (0 cases), respectively. The groups that underwent allogeneic bone graft without platelet-rich plasma included 3 cases of Stage I, 13 cases of Stage II, and 4 cases of Stage III, with associated success rates of 100% (3 cases), 38.4% (5 cases), and 0% (0 cases), respectively. Lower stages were associated with higher rates of successful operation for each group (p=0.02, p=0.04, respectively; Tables 3,4).

Table 1: Success Rate in Relation to Ficat and Arlet Stages in the PRP Group

| No. | No. of Successes | Success Rate (%) | P-Value* |
| :--- | :--- | :--- | :--- |
| I | 4 | 4 | 100 |
| IIA | 10 | 6 | 60 |
| IIB | 6 | 0 | 0 | 0.01 |
| Total | 20 | 10 | 50 |

Table 2: Success Rate in Relation to Ficat and Arlet Stages in the Non-PRP Group.

| No. | No. of Successes | Success Rate (%) | P-Value* |
| :--- | :--- | :--- | :--- |
| I | 5 | 4 | 80 |
| IIA | 11 | 4 | 36.4 |
| IIB | 4 | 0 | 0 | 0.02 |
| Total | 20 | 8 | 40 |

Table 3: Success Rate in Relation to ARCO Stage in the PRP Group.

| No. | No. of Successes | Success Rate (%) | P-Value* |
| :--- | :--- | :--- | :--- |
| I | 2 | 2 | 100 |
| II | 12 | 8 | 66.6 |
| III | 6 | 0 | 0 | 0.02 |
| Total | 20 | 10 | 50 |

Table 4: Success Rate in Relation to ARCO Stage in the Non-PRP Group

The pre-operative classification of necrotic area based on findings from MRI included 12 cases of Group A, 23 cases of Group B, 4 cases of Group C, and 1 case of Group D. The average percentage of necrotic area was 34.1% (range, 12.5% to 87.5%). The associated failure rate of each operation was 16.7% (2 cases) in Group A, 78.2% (18 cases) in Group B, 100.0% (4 cases) in Group C, and 100.0% (1 case) in Group D. Six cases in Group B (33.3%), 4 cases in Group C (100.0%), and 1 case in Group D (100.0%) underwent total hip arthroplasty.

The average dosage of platelet-rich plasma administered for allogeneic bone transplantation was 6.0 cc (range, 5.0 to 7.0 cc). The average dosage of allogeneic bone administered to all patients was 26.7 cc (20 to 30 cc; Tables 5,6). All 36 patients (40 cases) achieved fusion of the grafted bone; however, 9 patients (50%) in the group that received platelet-rich plasma and 12 patients (66.6%) in the group that underwent allogeneic bone graft only experienced failure of the operation. Among these patients, 4 (22.2%) who received platelet-rich plasma and 6 (33.3%) who underwent allogeneic bone graft only were changed to total hip arthroplasty.

*Result, Operative success and failure, including arthroplasty; †Preop, Preoperative; ‡Postop, Postoperative. Table 5: Details of the Patients in the PRP Group

The VAS scores that were used to assess pain alleviation over time were collected pre-operatively and at post-operative 3, 6, and 12 months. These scores were 7.44, 3.28, 3.06, and 6.95, respectively, for the group that received platelet-rich plasma and 7.06, 5.67, 3.89, and 7.00, respectively, for the group that had allogeneic bone graft only. Both groups showed significant pain alleviation through post-operative 6 months (p-value < 0.05). Pain alleviation at postoperative 3 months was significantly greater in the group that received platelet-rich plasma than in the group that had bone graft only; however, at post-operative 12 months, this difference was no longer apparent. The Harris Hip Scores were used to compare the mobility of patients. Pre-operative measurements were unavailable. However, the post-operative measurements at the 12-month follow-up did not differ significantly between the two groups (platelet-rich infusion group: 75; allogeneic bone graft only group: 76). No complications associated with infusion of the platelet- rich plasma, such as infections, were observed.

Discussion

Osteonecrosis of the femoral head triggers collapse of the femoral head and secondary coxitis resulting from necrosis of bone cells, causing structural change. The disease primarily occurs in patients undergoing artificial hip joint transposition surgery and mainly affects patients aged 30-50 years. The disease is a serious one because a large lesion can cause breakdown of the hip joint when the necrotic area invades the part of the bone responsible for weight bearing [6]. Treatment of femoral head osteonecrosis aims to preserve the femoral head through early diagnosis and to prevent expansion of the area of the lesion to avoid the need for total hip arthroplasty [7]. Many methods for articular salvage have been introduced. One such method, core decompression, is often used to treat initial lesions, and studies have documented diverse clinical results. In the current study, core decompression was performed in 38 patients (40 cases), 21 of whom (22 cases, 52%) demonstrated failure of the operation and 10 of whom (26.3%) underwent total hip arthroplasty. In addition, the rate of successful operations was higher for lower staged lesions and those with a smaller area. These results are consistent with those of Fairbank et al. [8] who reported a higher survival rate for lower staged lesions, and those of Rajagopal et al. [9] who reported that 26% of post-operative cases of core decompression eventually transitioned into total hip arthroplasty. Therefore, core decompression for osteonecrosis of early, pre-collapse disease stages [10] (i.e., lesions in Ficat Stage I [11]) is expected to lead to favorable outcomes through early treatment based on early diagnosis with MRI images [12]. Kim et al.[13] combined calcium phosphate transplantation with compressive bone graft to prevent post-operative collapse of the femoral head attributable to the weakening of subcartilaginous support. They found that the Harris Hip Score had increased at the final follow- up. Wei and Ge et al.[14] reported that a sole vascular, anchorage-independent bone graft resulted in better clinical outcomes in terms of survival rate and Harris Hip Score. In addition, an Indian study compared patients who underwent post-operative allogeneic bone graft with infusion of autologous, platelet-rich plasma after core decompression with patients who underwent bone graft after core decompression [15]. Those patients who received autologous, platelet-rich plasma showed better results as measured by simple radiographs and MRI images, VAS scores, and Harris Hip Scores. However, the authors did not explain the function of the autologous, platelet-rich plasma. Other authors have focused on the benefits of bone graft fusion in simple bone cyst operations [16] and proximal tibial osteotomy [17] induced by infusion of autologous, platelet-rich plasma combined with allogeneic bone transplantation. These authors expected the infusion of autologous, platelet-rich plasma to promote bone graft fusion through the core decompression track. The results of the current study showed an average of 3.0 months to the initiation of bone graft fusion for patients who received autologous platelet- rich plasma, which was shorter than the average of 5.5 months for patients who received bone graft only. Bone fusion can be defined as a change in the shape of bone trabeculae between the host bone and grafted bone or as a radiographic loss of the boundary between them [18]. In this study, the initiation of allogeneic bone fusion was determined by simple radiographic images captured during follow-up. The images showed no evidence of clinical progression or femoral head depression when the marrow cavity was restored. There was evidence of formation of newly generated bone after absorption of the grafted allogeneic bone, with the shape of bone trabeculae changing between the host and bone graft. However, Ranly et al.[19] reported that osteoinductivity, formation of newly generated bone, and the size of ossicles decreased 8 weeks after the infusion of human platelet- rich plasma combined with demineralized bone matrix (DBM) inserted into the gastrocnemius muscles of immunocompromised mice. They suggested that infusion of platelet-rich plasma disrupted bone formation. Further, Arpornmaeklong et al. [20] conducted experiments with mice and suggested that platelet-rich plasma disturbs the bone cell differentiation of pre-osteoblasts. Thus, the effects of platelet-rich plasma infusion on bone fusion require additional follow-up observations. In our study, both groups showed significant improvements in pain through post-operative 6 months; however, pain alleviation was greater in the group that received autologous, platelet-rich plasma at postoperative 3 months. Nonetheless, VAS scores and Harris Hip Scores did not differ significantly between the two groups at post-operative 12 months, suggesting that the administration of autologous, platelet-rich plasma did not stop the natural progression of femoral head necrosis. In this study, 38 patients (40 cases) with femoral head necrosis were examined to identify the effects of platelet- rich plasma infusion combined with allogeneic bone transplantation after core decompression. However, further comparative studies that enroll a larger number of patients and include control and experimental groups are needed. Studies should also consider the effects of platelet-rich plasma on osteonecrosis by considering its functions in the joint cavity, which should be identifiable percutaneously or through arthroscopy for the treatment of femoral head necrosis.

Conclusion

Through the post-operative core decompressive track generated after core decompression to treat initial femoral head osteonecrosis, allogeneic bone graft can be administered with autologous, platelet-rich plasma to promote bone fusion and to maximize the effects of the treatment. In the current study, administration of autologous platelet-rich plasma also led to initial post- operative pain alleviation. However, suspension of the natural progression of femoral head necrosis, including the transition into femoral head depression, through the administration of platelet-rich plasma appears unlikely. Thus, further studies on the effects of platelet-rich plasma infusion for the treatment of femoral head osteonecrosis are required.