Introduction
Scaphoid fractures are among the most frequently encountered carpal fractures, often accompanied by complications such as non:union: or delayed :union: [1]. These fractures are highly prevalent and typically present with pain, functional impairment, and limited wrist mobility [2]. Conventional treatment often involves prolonged immobilization with a cast, which can lead to joint stiffness, further motion restriction, and delays in returning to work or daily activities [3, 4].
To address these challenges, novel orthobiologic therapies have been investigated, demonstrating the potential to accelerate fracture and non:union: healing. Platelet-rich plasma (PRP) is one such treatment that has shown promise in a limited number of studies for enhancing fracture :union: and improving long-term patient outcomes [5, 6]. Additionally, bone morphogenetic proteins (BMPs) have been utilized to promote :union: in lumbar fusions and tibial fractures [7, 8]. However, their effectiveness in reducing scaphoid non:union: has produced mixed results.
This narrative review aims to evaluate the clinical and functional outcomes reported in studies examining the application of orthobiologic therapies in the management of scaphoid non:union:s.
Current treatment of scaphoid fracture and non:union:
If a scaphoid fracture is minimally displaced, immobilization through casting or a splint is a common treatment approach [9]. However, fracture :union: with this method typically requires 8 to 12 weeks, a duration that may be inconvenient for young and active individuals [10]. Once a :union: is achieved, hand physiotherapy can commence to restore function [9]. However, complications such as muscle atrophy, joint stiffness, and diminished grip strength may arise, potentially delaying the patient’s return to work and normal daily activities [11].
Various surgical fixation methods, including screws, bone grafts, and alternative approaches, have been discussed in the literature [12, 13]. Bone grafting, often sourced from the radius, is employed to enhance blood supply to the fracture site [14]. Screw fixation, particularly with headless compression screws inserted along the central longitudinal axis of the scaphoid, provides structural stability by compressing fracture fragments and preventing bending at the site [15]. This method is the most common fixation technique for scaphoid fractures [12]. Kirschner wires (K-wires) may also be used for stabilization, particularly in cases of ligamentous instability or minor soft tissue injuries [11]. However, K-wires are associated with risks such as pin site infections, stiffness, and the potential need for reoperation [12]. For fractures with significant comminution or bone loss, volar plating can provide additional support [14].
Overall, internal fixation methods achieve high :union: rates, typically ranging from 85% to 90%, and enable an earlier return to activity compared to non-surgical approaches [11, 15]. Nevertheless, complications such as vascular injury or fracture instability can contribute to non:union:, requiring advanced treatment strategies [12]. In cases of non:union:, salvage procedures such as proximal row carpectomy, scaphoid excision with arthrodesis, or total wrist fusion may be necessary. However, these methods often result in permanent limitations to wrist function [14].
Currently, fixation with a headless compression screw, with or without bone grafting, is considered the standard treatment for scaphoid fractures [14, 16]. If additional stability is required, a volar plate can be combined with screw fixation to provide extra support [14]. These combined techniques aim to address both the structural and vascular challenges associated with scaphoid fractures while minimizing long-term complications.
BMP for scaphoid non:union:
Bilic et al. [17] conducted a study in 2006 involving 17 patients diagnosed with proximal scaphoid non:union:. The participants were randomly allocated into three distinct treatment groups: 6 patients received an autologous iliac crest bone graft, another 6 received an autologous iliac crest bone graft supplemented with osteogenic protein 1 (OP-1, also known as BMP-7), and the remaining 5 were treated with an allogenic iliac crest bone graft combined with OP-1. Radiographic and clinical evaluations were performed over a 24-month follow-up period. The findings demonstrated that human recombinant OP-1 (or BMP-7) facilitated the repair of proximal scaphoid non:union:s by promoting bone angiogenesis and replacing sclerotic bone caused by avascular necrosis. Patients treated with autologous bone and OP-1 showed significantly enhanced radiological healing and reduced healing times, achieving :union: in 4 weeks compared to 9 weeks for those treated with autologous bone alone. This reduction in healing time has the potential to shorten the immobilization period, thereby decreasing the risk of complications such as radiocarpal and radioulnar arthritis, joint stiffness, and Sudeck’s atrophy. It also minimizes muscle atrophy in the forearm and hand, allowing for a quicker return to work. In group 3 (allogenic graft with OP-1), radiographic improvement was observed at 8 weeks post-surgery, outperforming group 1 (autologous graft alone). This result suggests that combining allogenic bone grafts with OP-1 can eliminate the need for autologous grafts, which are associated with donor site complications, including increased surgical blood loss, postoperative pain, and an increased risk of infection. Additionally, OP-1 significantly improved the functional performance of the injured hand compared to autologous grafting alone.
Conversely, a study by Chevet-Noël et al. [18] investigated 5 patients (mean age: 32 years, range: 21–44 years) with old scaphoid non:union: (over 24 months) following unsuccessful autograft treatment. The treatment involved reaming the non:union: site, applying a bone autograft supplemented with BMP-7 at the defect, and stabilizing it with a screw or K-wire, followed by postoperative immobilization. Despite a long average follow-up of 10 years (ranging from 80 to 143 months), only one patient (20%) achieved bone :union:. Functional outcomes revealed an average flexion-extension loss of 16.68 degrees (range: 0–30 degrees) and average hand strength reductions of 450 g (range: 0–2000 g) for pinch and 12.1 kg (range: 0–29 kg) for grip compared to the contralateral hand. The mean patient-rated wrist evaluation (PRWE) score was 28.9 (range: 10.5–49), and the mean QuickDASH (disabilities of the arm, shoulder, and hand) score was 28.6 (range: 9.09–61.36). The study concluded that BMP-7 offered no significant advantages for treating old scaphoid non:union:, particularly given its high cost and limited success.
In 2015, Ablove et al. [19] performed a retrospective analysis to assess the outcomes of 4 patients who experienced failed open reduction and internal fixation (ORIF) for scaphoid fractures. Of these cases, three involved fractures at the scaphoid waist, while one was located at the proximal pole. All patients underwent screw replacement and placement with the addition of BMP-2, without the need for supplementary bone grafting. Patients were immobilized for four weeks, with serial radiographs taken for all and follow-up computed tomography (CT) scans in three cases. :union: was achieved in all patients within an average of 53 days post-surgery, and they eventually returned to full, pain-free activity. No complications were reported, and the use of BMP-2 and screw exchange resulted in a 100% :union: rate. Although the study was limited by its small sample size and retrospective design, it highlights a potentially effective approach for managing scaphoid non:union:.
In a 2016 retrospective study by Brannan et al. [20], 6 cases of revision surgery for scaphoid non:union: were examined. These patients, who had persistent non:union: following initial ORIF for scaphoid fractures, were treated with revision screw surgery, bone grafting, and recombinant human BMP-2 (rhBMP-2). :union: was confirmed via CT scans in all cases. However, complications were common, including persistent non:union: (2 cases), significant heterotopic ossification (4 cases, with 1 requiring revision surgery), and loss of functional movement (1 case). Two patients with persistent non:union: underwent scaphoidectomy and midcarpal arthrodesis. Notably, delayed wound healing was not observed in any of the cases. Only 1 out of 6 patients healed without complications. The time between the initial injury and the first ORIF ranged from 3 months to 4 years, with an average of 24 months. Despite the high :union: rate, the study highlighted significant challenges, particularly the high prevalence of heterotopic ossification and other complications. These findings suggest that while rhBMP-2 shows potential in scaphoid non:union: revision surgeries, its risks and limitations warrant further investigation.
PRP for scaphoid non:union:
In a 2016 study by Namazi et al. [21], a randomized controlled trial was conducted involving 14 patients with Herbert type B2 scaphoid fractures. Participants were divided into two groups, with one group receiving intra-articular injections of 1.5 mL PRP and the other receiving 1.5 mL normal saline. Both groups were subsequently immobilized with long-arm casts. Radiological evaluations were performed at 2-week and 2-month follow-ups, and CT scans were conducted at the 2-month follow-up to assess fracture :union:. Clinical assessments were performed using the PRWE questionnaire for pain and functional outcomes, as well as measurements of range of motion at 3 and 6 months post-treatment. The results demonstrated significant improvements in pain at rest and during specific activities in the PRP group compared to the control group. However, no statistically significant differences were observed in wrist movements, including radial and ulnar deviation, flexion, and extension, except for an improvement in ulnar deviation at the 3-month follow-up. Although scaphoid :union: appeared to occur earlier in the PRP group, the difference was not statistically significant.
In a separate study by de Vitis et al. [22] in 2020, patients undergoing surgical treatment for scaphoid fractures were divided into two groups. Group A underwent osteosynthesis via the volar approach using shape memory staples (SMS), while Group B received SMS combined with gelled PRP (GPRP) at the bone defect site. Both groups underwent cast immobilization (without including the thumb) for 4 weeks. Outcomes were assessed based on pain levels, QuickDASH scores, Mayo wrist scores, and radiographic evaluations. Bone :union: was observed in 95.2% of patients in group A (40 out of 42) and in 100% of patients in group B (45 out of 45). Group B demonstrated a statistically significant improvement in the Mayo wrist score, QuickDASH score, and pain levels (as measured by the visual analog scale, [VAS]) at 3 months post-surgery (P = 0.02). These findings suggest that the addition of GPRP to SMS osteosynthesis may enhance both clinical and functional outcomes in the treatment of scaphoid fractures.
In a retrospective study conducted by Zhong et al. [23] in 2023, patients with grade III (25 patients) and grade IV (28 patients) scaphoid non:union:s (SNU) were evaluated based on the Slade and Dodds classification. The study included patients treated between January 2015 and May 2020 using three different methods: Open bone grafting (BG) and internal fixation (group A), percutaneous screw fixation (group B), and percutaneous screw fixation combined with PRP injection (group C). Outcomes were assessed by comparing the fracture stabilization rate, VAS score for pain, and Mayo wrist function score among the three groups. The :union: rates for SNU grades III and IV did not differ significantly between the groups. However, patients in group C reported significantly less pain and better wrist function 7 days post-surgery compared to patients in groups A and B, for both grades of non:union:. At the 3-month follow-up, group C showed significantly superior VAS and Mayo wrist scores compared to group A across both grades, and also outperformed group B in cases of grade IV SNU. At 6 and 12 months after surgery, patients with grade IV SNU in groups A and C continued to exhibit notably better VAS and Mayo wrist scores than those in group B. In a case series by Aslam et al. [24], conducted from 2007 to 2011 at Hong Kong Hospital, 4 patients with scaphoid fractures were treated with ORIF, BG from the iliac crest, and PRP injections. The study included patients with an average age of 35.7±7.7 years (range: 31 to 47 years) and an average follow-up of 21.75±14.97 months (range: 5 months to 3.5 years). Clinical and radiological evaluations were conducted to assess :union: and pain-free range of motion. The results showed that all patients achieved :union: and restored pain-free wrist mobility, highlighting the potential of this combined approach in managing scaphoid fractures.

Conclusion
After reviewing the articles mentioned above, it is evident that the use of orthobiologics in treating scaphoid non:union: yields contradictory results, making it difficult to draw a definitive conclusion. While some studies report improved :union: rates following the use of PRP or BMP, others show no significant differences in outcomes with the application of these agents. Moreover, potential complications associated with orthobiologics, such as heterotopic ossification and reduced wrist motion, warrant careful consideration. A major limitation of the current evidence lies in the retrospective nature and small sample sizes of most studies, which reduce the reliability and generalizability of their findings. To address these shortcomings, future research should prioritize well-designed randomized controlled trials with larger sample sizes to provide more robust and conclusive evidence. Additionally, further exploration of innovative therapeutic strategies is recommended. Potential strategies may involve creating advanced scaffolds that integrate vascular endothelial growth factor (VEGF) and BMPs or exploring the effectiveness of different BMP variants. These approaches have the potential to enhance the efficacy of orthobiologics in treating scaphoid non:union: while minimizing associated complications.

Ethical Considerations

Compliance with ethical guidelines
This article is a meta-analysis with no human or animal sample.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, visualization and writing the original draft: Morteza Behjat; Supervision, project administration, funding acquisition, review and editing: Alireza Pahlevansabagh.

Conflict of interest
The authors declared no conflict of interest.





References