The clinical effect of ossotide for injection in the treatment of condylar fracture

Abstract

OBJECTIVES:

Patients with condylar fractures were treated with osteopeptide injections as an adjuvant therapy to assess pain control and changes in interleukin-1β (IL-1β) and bone G-gla protein (BGP) levels.

MATERIALS AND METHODS:

Eighty-two patients with a condylar neck fracture were randomly assigned to two groups. The control group received conventional surgical treatment, while the experimental group received osteopeptide injections in addition to surgery. Pain level, IL-1β, and BGP levels were evaluated at 1, 2, and 4 weeks postsurgery.

RESULTS:

One and two weeks postsurgery, the experimental group had lower Numeric Rating Scale scores compared to the control group. In addition, the IL-1β level in patients receiving osteopeptide injections was lower than the control group at all three evaluation points (1, 2, and 4 weeks postsurgery) and the BGP level was higher with statistically significant differences (P < 0.05).

CONCLUSIONS:

The administration of osteopeptide injections as an adjuvant therapy for patients with condylar fractures can effectively reduce pain and facilitate faster initiation of muscle function training. In addition, the reduction of inflammatory factors and promotion of active osteogenesis leads to quicker wound healing.

Introduction

The condyle is a vulnerable area in the maxillofacial region, prone to fracture. With advancements in treatment methods, drugs, materials, and imaging technology, the diagnostic and therapeutic approach for condylar fractures must adapt. In addition to surgical treatment, it is crucial to alleviate patients’ pain and enhance tissue repair postsurgery to prevent and resolve potential sequelae. This study used osteopeptide injections as an adjuvant treatment for patients with condylar fractures and assessed its clinical efficacy.

Materials and Methods

During 2020–2022, 82 patients (calculated by using the website http://powerandsamplesize.com) admitted to our hospital with condylar fractures were randomly divided into two groups, using random number table. The experimental group consisted of 41 individuals, including 20 males and 21 females, with an average age of 33.54 ± 5.12 years (ranging from 20 to 61 years old). The control group consisted of 41 patients, including 22 males and 19 females, with an average age of 34.11 ± 4.45 years (ranging from 23 to 62 years old). Before the trial, the patients were thoroughly informed of the treatment methods, goals, risks, and consequences, and provided informed consent. The inclusion criteria are as follows: (1) Fracture of the condylar neck (2) Requiring surgical reduction and fixation. The exclusion criteria are: (1) Intracondylar fracture (high fracture, fracture line located on the condylar joint surface), (2) Subcondylar (base) fracture, (3) Comminuted condylar fracture, and (4) Cases where surgery is not performed.

The control group was treated with conventional surgery (fracture of the middle and low condyle).[1] The selected cases in this study are all condylar neck fractures, which belong to middle and low-level fractures. The submandibular incision, posterior mandibular incision, or intraoral incision (assisted by endoscope) can be used for fixation with a titanium plate and bicortical screw to improve the stability of fixation, and then intermaxillary traction or ligation can be performed for observation for 1–2 weeks. The experimental group was treated with bone peptide injection (Jiangxi Judu Pharmaceutical Co., Ltd., approval number: Guoyao Zhunzi H36022454, 2 mL/piece) as an adjuvant treatment after routine surgery and reduction and fixation. Prepare 250 mL of 0.9% sodium chloride, add 30 mL of osteopeptide into it by injection, and then give the patient intravenous drip, qd, lasting for 4 weeks.

The evaluation of patients was conducted at 1, 2, and 4 weeks after the surgery. The following indicators were recorded: (1) Numeric Rating Scale (NRS) score, to measure the level of pain experienced by the patients, (2) Interleukin-1β (IL-1β) levels in the venous blood, and (3) Bone G-Gla Protein (BGP) levels in the venous blood. The NRS score was determined based on the level of pain experienced by the patient, where mild pain was rated 1–4 points, moderate pain was rated 5–6 points, and severe pain was rated 7–10 points. The blood samples were collected after fasting, and the levels of IL-1β and BGP were measured using the rabbit anti-human IL-1β Polyclonal Antibody from Shenyang Wanlei Biotechnology Co., Ltd (WL00891) and BGP test kit from ESYJXZZ 2401995, respectively. The blood was separated at 4°C and preserved with aprotinin.

The statistical data in this study were processed using SPSS (Version 23.0; IBM, Armonk, NY, USA). The NRS score, IL-1β, and BGP were presented as mean ± standard error (x ± s), and paired t-test and Chi-squared test were performed to analyze the results. A P < 0.05 was considered to indicate statistical significance.

Results

The results showed that at 1 and 2 weeks after operation, the NRS score of the experimental group was significantly lower than that of the control group (P < 0.05), indicating that the experimental group had less pain than the control group. However, 4 weeks after operation, there was no statistical difference in NRS score between the two groups (P > 0.05), indicating that the difference in pain levels between the two groups was not significant.

Table 1 shows the comparison of NRS score between the experimental group and the control group at 1, 2, and 4 weeks after operation. The results indicate that the experimental group had a lower NRS score compared to the control group at 1 and 2 weeks postoperation (P < 0.05), while there was no statistical difference in NRS score between the two groups at 4 weeks postoperation (P > 0.05). The mean NRS score in the experimental group was 4.29 ± 0.53 at 1 week, 2.21 ± 0.52 at 2 weeks, and 0.42 ± 0.20 at 4 weeks. In the control group, the mean NRS score was 7.56 ± 1.13 at 1 week, 3.77 ± 0.86 at 2 weeks, and 0.38 ± 0.24 at 4 weeks. The t-value for 1 week was 23.65, for 2 weeks was 14.00, and for 4 weeks was 1.15. The corresponding P = 0.00, P = 0.00, and P = 0.07 [Supplementary Table 1].

Table 1.

Comparison of Numeric Rating Scale score between experimental and control groups at different time points

Group	1 week	2 weeks	4 weeks
Experimental (n=82)	4.29±0.53	2.21±0.52	0.42±0.20
Control (n=82)	7.56±1.13	3.77±0.86	0.38±0.24
t	23.65	14.00	1.15
P	0.00	0.00	0.07

Table 1.

NRS score of experimental and control groups of 1 week

Group Statistics
Group	n	Mean	Std. deviation	Std. Error Mean
NRS score
Experimental Group 1 Week	82	4.2917	0.53449	0.05902
Control Group 1 Week	82	7.559	1.13135	0.12494

Comparison of IL-1β and BGP conditions after surgery 1, 2, and 4 weeks after surgery, the IL-1β levels in the experimental group were higher than those in the control group, with statistically significant differences (P < 0.05). The BGP levels in the experimental group were lower than those in the control group, with statistically significant differences (P < 0.05), as shown in Table 2 and Supplementary Table 2.

Table 2.

Interleukin-1β compared with bone G-Gla protein level (x±s, µg/L)

Group	1 week		2 weeks		4 weeks
	IL-1β	BGP	IL-1β	BGP	IL-1β	BGP
Experimental (n=82)	319.42±26.04	2.86±0.62	234.90±51.14	3.36±0.69	177.28±42.92	6.31±1.35
Control (n=82)	386.24±43.08	2.09±0.44	327.49±59.59	2.55±0.52	219.16±69.21	4.32±0.50
t	12.02	9.17	10.68	8.49	4.66	12.50
P	0.02	0.00	0.01	0.01	0.00	0.00

BGP=Bone G-Gla protein, IL-1β=Interleukin-1β

Table 2.

Independent Samples Test of NRS of 1 week

Independent Samples Test
	Levene’s Test for Equality of Variances		t-test for Equality of Means
	F	Sig.	t	df	Sig. (2-tailed)	Mean difference	Std. Error difference	95% Confidence Interval of the Difference
								Lower	NRS score
NRS score
Equal variances assumed	37.199	0	-23.646	162	0	-3.26732	0.13818	-3.54018	-2.99446
Equal variances not assumed			-23.646	115.442	0	-3.26732	0.13818	-3.54101	-2.99362

Discussion

Osteopeptide is a light yellow, transparent injection extracted from fresh or lyophilized pig limb bones. It is made into a sterile, lyophilized product and can be mixed with normal saline or other solvents for intravenous injection. The drug is used in clinics to repair bone injuries and promote fracture healing, as well as to regulate the balance of calcium and phosphorus in bones.[2,3] Research has shown that osteopeptide is effective in treating various conditions, such as osteoporosis, hyperosteogeny, osteoarthritis, rheumatoid arthritis, and postoperative fractures.[4,5] It has been found to relieve pain, improve bone metabolism, reduce inflammation, and promote the recovery of spinal function.[6] Although osteopeptide has proven to be effective in treating fractures of the limbs, spine, and lumbar spine, there are few reports on its use for condylar fractures.[7,8,9]

The condylar process is a region in the maxillofacial area that is prone to fracture, resulting in severe and rapidly worsening pain for patients. Symptoms may include hypothermia, pale complexion, and even shock due to the intensity of pain. Therefore, reducing pain during surgical treatment, promoting tissue repair, and preventing postoperative complications is essential.[10,11] A lack of activity can lead to muscle disuse atrophy, making functional recovery training necessary after the operation. However, the inflammatory reaction and pain can make patients reluctant to undergo muscle function training, hindering the recovery process. Alleviating the pain of condylar fracture patients is not only a medical concern but also a matter of humanistic care and a key factor for postoperative recovery. Studies have shown that the use of osteopeptide injection in the early postoperative period can significantly reduce pain, as measured by the NRS score, allowing for more effective functional recovery training and reducing the risk of muscle atrophy. By the 4^th week after surgery, there was no significant difference in pain levels between the experimental group and the control group, which may be due to natural body repair and pain tolerance.

Bone peptide injection, extracted from mammalian bones, contains a variety of trace elements and active peptides that have potent anti-inflammatory and pain-relieving effects. BGP is a noncollagen protein produced and secreted by osteoblasts and is a commonly used indicator of bone metabolism in clinical practice.[12,13,14] An increase in BGP levels in the serum is a sign of good fracture growth and a key factor in promoting fracture healing.[15,16,17] This study found that the use of osteopeptide injection led to higher BGP levels in patients compared to the control group, suggesting that it can improve bone metabolism, enhance local blood circulation, and aid in the healing of condylar fractures.

The condylar fracture will stimulate the inflammatory reaction in the body, which will damage the normal function of the body tissue and delay the fracture healing. IL-1β is a major inflammatory factor in the body.[18,19] It appears and enhances the inflammatory reaction during inflammation and, when activated, can promote osteoclast formation and differentiation, stimulate bone resorption, reduce bone density, damage vascular endothelial function, and promote thrombus formation. During the acute phase of inflammation, its content will significantly increase and cause the aggregation of inflammatory cells.[20,21] It can regulate inflammation, induce white blood cell synthesis, and cause hypercoagulability and immune reactions. Therefore, after fracture, IL-1β may disrupt the balance between bone formation and bone resorption, which is not conducive to fracture healing.[22] In this study, after auxiliary use of bone peptide injection, the IL-1β in the patient’s serum was significantly reduced, effectively controlling the inflammatory factors, reducing the inflammation reaction, and promoting bone formation.

Conclusions

The use of bone peptide injection as an adjuvant treatment following routine surgery for condylar fractures can significantly alleviate pain, enhance bone metabolism, and effectively control inflammation, promoting a quicker and more efficient healing process [Figure 1].

Figure 1.

Graphical abstracts

Financial support and sponsorship

The study was supported by:

Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project (No. S2022153).

Guilin Scientific Research and Technological Development Plan Project (No. 2020011203-5).

Guilin Medical College Young and middle-aged faculty research ability improvement project (No. 2018glmcy018).

Healthentalent plan of Taihu Lake in Wuxi (Double Hundred Medical Youth Professionals Program) from Health Committee of Wuxi. General Project of Wuxi Municipal Commission of Health and Family Planning (M202240).

Research project funded by the Health Commission of Guangxi Zhuang Autonomous Region(Z-C20231971).

Conflicts of interest

There are no conflicts of interest.