Bone marrow aspirate concentrate for the treatment of fifth metatarsal head stress fracture: a case report

Abstract

Metatarsal head stress fractures pose treatment challenges with no established consensus. In this article, we introduce a percutaneous treatment involving autologous bone marrow aspirate concentrate (BMAC) injection without surgical fixation in a 21-year-old basketball player with a stress fracture of the right fifth metatarsal head. He underwent this procedure following unsuccessful 8 months of conservative treatment. Twelve weeks after the procedure, a CT scan confirmed complete healing, facilitating his return to sports. This innovative method offers a promising alternative, avoiding the associated morbidity of surgical intervention. Further research, comparing refracture rates with surgical options, is warranted to inform treatment decisions for this uncommon injury and validate the efficacy of percutaneous BMAC injection.

Plain Language Summary

What is the study about? Metatarsal head stress fractures are uncommon and challenging to treat, often requiring surgery if conservative methods fail. This report introduces a successful alternative: a percutaneous injection of bone marrow aspirate concentrate (BMAC) directly into the fractured area, avoiding surgical risks. BMAC contains stem cells and growth factors that promote healing. In this case, a collegiate basketball player with a fifth metatarsal head fracture underwent this procedure after conservative treatments failed over 8 months.

What were the results? Twelve weeks after the procedure, CT scan showed complete healing, allowing the player to return to sports without complications.

What do the results mean? This innovative approach offers a promising option for refractory fractures, potentially sparing patients from surgery and its associated complications. Further research comparing refracture rates with surgical methods is needed to guide treatment decisions for this rare injury effectively.

Plain language summary

Article highlights.

Fifth metatarsal head fractures

• Rare foot injury with no consensus on the best approach for its management.

• Typically treated conservatively first before surgical interventions are pursued.

Percutaneous bone marrow aspirate concentrate procedure detail

• A source of mesenchymal stromal stem cells and growth factors that has been utilized to enhance orthopedic procedures.

• Collected from posterior iliac crest.

• Injected into the intra-osseous space of the fifth metatarsal head under ultrasound-guidance.

Clinical implications

• Percutaneous BMAC injection presents a novel treatment option for refractory metatarsal head stress fractures.

• Offers a promising alternative to surgical intervention, avoiding associated complications.

• Further research needed to compare refracture rates between percutaneous BMAC injection and surgical fixation.

1. Introduction

Metatarsal head stress fractures are rare foot injuries, and there is currently no consensus on the best approach for its management [1,2]. If conservative treatments prove ineffective, surgical interventions such as open reduction and internal fixation (ORIF) are commonly performed [3]. In this case report, we describe the successful management of a fifth metatarsal head stress fracture using an autologous bone marrow aspiration concentrate (BMAC) percutaneous intraosseous injection without surgical fixation. This method avoids the potential morbidities associated with surgery including screw failures and residual stiffness of the metatarsophalangeal joints [3]. BMAC contains mesenchymal stromal stem cells (MSCs), hematopoietic stem cells (HSCs) and growth factors that promote bone and soft tissue healing by creating a microenvironment that preferentially induces the differentiation of stem cells into osteogenic progenitor cells [4]. To date, there have been no published studies on the use of percutaneous BMAC injection for the treatment of head stress fractures. This case report is presented in accordance with the CARE reporting checklists.

2. Case presentation

A 21-year-old collegiate division I basketball player with a history of Crohn's disease developed insidious right foot pain during pre-season training. His pain was localized to the lateral aspect of his foot around the fifth metatarsal head, and ranged from a 0/10 to a 5/10 in intensity. He described his pain as throbbing and aching, and provoked by impact activities such as jumping and running. After 2 weeks of relative rest, he attempted to return to play but was unable to progress his activity due to the pain. Three view radiograph of the right foot was unremarkable (Figure 1). MRI of the right foot demonstrated a subacute fracture of the fifth metatarsal head (Figures 2 & 3). The patient was managed by his team surgeon for over 8-months with conservative treatments, including immobilization with a walking boot, a trial of a bone stimulator (Exogen Ultrasound Bone Healing System, Bioventus, NC), 6 cold laser treatments (OrthoLazer Orthopedic Lazer Center, MA), 4 extracorporeal radial shockwave therapies, blood flow restriction therapy and footwear modification. At 8-months post-injury, the patient remained in the walking boot and the pain had not improved. The follow-up MRI showed cortical buckling and a subacute fracture of the fifth metatarsal head with reactive bone marrow edema, raising concerns for a progression of the disease.

Figure 1.

Pre-procedural oblique radiograph of the right foot was unremarkable.

Figure 2.

Pre-procedural coronal MRI view of the right foot displaying a subacute fracture of the fifth metatarsal head accompanied by reactive bone marrow edema and erosive changes.

Figure 3.

Pre-procedural sagittal MRI view of the right foot displaying a subacute fracture of the fifth metatarsal head accompanied by reactive bone marrow edema and erosive changes.

The patient presented to our clinic for a second opinion. On exam, he had normal alignment of the foot. He was able to stand on his toes, but reported pain on the lateral aspect of the foot. There was tenderness to palpation over the right fifth metatarsal head. There was no swelling or ecchymosis. He had full motor strength. Sensation was normal. A single leg hop test was positive. Treatment options were discussed, including ongoing conservative management, orthobiologic procedure and surgical management. Due to the refractory disease course, the patient elected to proceed with an autologous BMAC intraosseous injection at the site of bony erosion.

An informed consent was obtained from the patient. Bone marrow aspiration was performed from the right posterior iliac crest. After identifying the bony landmarks on ultrasound guidance, the area over the harvest site was prepped with antimicrobial solution and sterile draping. A skin wheal was placed with 2 ml of 1% lidocaine with epinephrine using 30-gauge 1 inch needle. The periosteum was anesthetized with 10 ml of 1% lidocaine and 10 ml of 0.5% ropivacaine. A stab incision with an 11 blade was made through the wheal. A trocar was inserted through the skin and was guided through the posterior superior iliac spine (PSIS) under ultrasound guidance. A 17-gauge infiltration cannula was inserted into the PSIS, and 60 ml of bone marrow was aspirated from the right iliac crest. Sterile gauze was used to cover the tissue harvest area. The bone marrow collected was processed in the closed system (PUREBMC SupraPhyisiologic, EmCyte, FL) according to the processing protocols. 6 ml of BMAC was produced. A therapeutic injection of 2.5 ml of BMAC was given under sterile technique using a 25-gauge 1.5-inch needle into the intra-osseous space of the fifth metatarsal head using ultrasound-guidance and a sterile bandage was applied over the punctured skin. The patient tolerated the procedure well without any immediate adverse reaction.

Following the procedure, the patient was immobilized in a walking boot until the next follow-up. He reported moderate improvement in pain and range of motion 6-weeks post-procedure. Post-procedural radiograph of the right foot showed osteopenia at fifth metatarsal head and persistent erosive changes, but did not show a clear fracture line. He was weaned off of the walking boot, and started a progressive rehabilitation program. By 8-weeks post- procedure, he progressed to jumping activities. A follow-up CT scan 12-weeks post-procedure showed resolution of the distal fifth metatarsal fracture (Figure 4). He was cleared to return to sport without restrictions and returned to playing with his D1 basketball team. There was no recurrence of pain at the 6- and 12-month follow-up. We obtained consent from the patient to write this case as a case report.

Figure 4.

Post-procedural CT scan of the right foot showing resolution of the fifth metatarsal head fracture.

3. Discussion

A stress fracture is an injury that occurs when repetitive excessive loads are applied to a normal skeleton. It is believed to result from an imbalance in bone metabolism, where microdamage accumulates faster than it can be repaired and replaced through the body's natural bone remodeling process [5]. Metatarsal head stress fractures are a relatively uncommon injury [1,2]. It is hypothesized that these fractures can occur during the toe-off phase of the gait cycle when the metatarsal head experiences compression against the proximal phalanx. This repeated compression can result in shearing stress parallel to the subchondral bone, leading to subchondral insufficiency fractures [6]. Athletes, especially basketball players, are at a higher risk of developing fifth metatarsal base fractures due to their increased activity level and larger body size compared with the general population [7]. However, it is not entirely clear if this same risk factor applies to metatarsal head stress fractures.

There is no consensus regarding the optimal management for this type of injury [2]. A reasonable conservative management plan would include a short-leg, non-weight-bearing cast or cast boot with the use of crutches for four to six weeks, with follow-up intervals of four to six weeks that include radiographs and examination out of the cast at each visit. If there are radiographic and clinical signs of healing, protected weight-bearing can be initiated for two to four weeks. Referral to orthopedics should be considered if healing has not occurred by 3–4 months [8]. Missaoui et al. conducted a review of the literature and observed that previous case reports have employed both conservative and surgical treatments for acute metatarsal head fractures [3]. Conservative treatments typically involve weight-bearing restrictions, often with the use of a hard-soled shoe, walking boot, or walking cast. These conservative measures can be continued for two to three weeks, especially if significant pain persists [9]. One study reported a successful closed reduction with local anesthetic followed by immobilization for a patient who experienced a dorsal dislocation of third metatarsal head after a fall from a tree [10]. ORIF is the most commonly used surgical option for the treatment of metatarsal head fractures [3]. However, it is worth noting that there have been a few reports of complications associated with ORIF, including plantar protrusions of screw tips and residual stiffness of the metatarsophalangeal joint [3]. The use of BMAC without surgical intervention is a novel approach that avoids morbidities associated with surgeries.

To our knowledge, this is the first study that used intraosseous BMAC injection for the treatment of a metatarsal head stress fracture. There is a case report on the use of percutaneous BMAC injection for an isolated cuboid stress fracture. In this case, however, the BMAC was injected into the dorsal cuneocuboid joint space rather than intraosseously. The BMAC injection was followed by a leukocyte-poor PRP injection into the cuneocuboid joint and the dorsal intermetatarsal ligaments between the third and fourth metatarsals 10 days later [11]. Several studies have been published on the use of percutaneous BMAC injections to augment internal fixation. Murawski and Kenenedy published a retrospective study involving 26 non-professional athletes with Jones fractures who were who were treated with internal fixation augmented with BMAC. 96% of the patients had complete bony consolidation at 8 weeks post-operatively, and they were able to return to play at 10.1 weeks on average. However, there was one case of refracture and one case of delayed union [12]. In a similar but more recent study, O'Malley et al. published a retrospective study in which 10 professional basketball players with Jones fractures who were treated with internal fixation augmented with BMAC. Although all cases showed complete healing at 7.5 week on average and players were able to return to play at 9.8 weeks on average, refractures were seen in 3 cases. The authors concluded that refractures are not uncommon even after radiographic signs of complete bone healing and recommended delaying return to play for 12-weeks after the procedure [7]. In a case report, a medial cuneiform stress fracture was successfully treated with a combination of internal fixation and BMAC [13]. These studies suggest that internal fixation augmented with BMAC may be a promising therapeutic treatment to manage several types of fractures in athletes, but there is a concern for risk of refracture even after radiographic confirmation of healing. Table 1 summarizes studies that augmented internal fixation with percutaneous BMAC injection for the treatment of fractures.

Table 1.

Summary of studies that used percutaneous BMAC injection to augment internal fixation for the treatment of stress fractures.

Study (year)	Study design and patient characteristics	BMAC characteristics and injection technique	Post-injection management	Findings/complications	Conclusions	Ref.
Murawski and Kennedy (2011)	Retrospective 26 Jones fractures in athletes treated with percutaneous internal fixation with BMAC.	60 ml of bone marrow was aspirated from ipsilateral iliac crest (Harvest SmartPReP 2 BMAC system, Harvest Technologies Corporation, MA). The surgery was performed with fluoroscopy-guidance. Aspirate or concentrate were not analyzed.	Patients wore splint for 2 weeks after the surgery, then a walking boot for 4 weeks. Non-weight bearing was maintained for 4 weeks, then patient was allowed to progress to partial weight bearing from 4 to 6 weeks postoperatively to full weight bearing by 6 weeks postoperatively. Return to athletic competition was considered at 8 weeks after surgery based on clinical and radiographic findings.	25/26 (96%) patients had complete bony consolidation at 8 weeks postoperatively. The mean time to fracture healing was 5 weeks and the mean to return to play was 10.1 weeks. 2 patients were unable to return to their previous level of activity. There were 1 case of delayed union and 1 case of refracture.	Percutaneous internal fixation with BMAC permits athletes to return to sport at their previous levels of competition with few complications.	[12]
Adams et al. (2013)	Case Report A 36F with medial cuneiform stress fracture who was treated with internal fixation using a cannulated screw and BMAC delivered via the cannulated screw.	30 ml of bone marrow aspirate was collected from ASIS and was concentrated down to 4–6 ml of BMAC. Concentrate injected with fluoroscopy-guidance. Aspirate or concentrate were not analyzed.	The patient was noncompliant with postoperative instructions to remain non-weight bearing and admitted to ambulating on the foot soon after the procedure.	Postoperative radiographs and CT obtained 10 weeks postoperatively confirmed union at the fracture site.	Percutaneous delivery of BMAC to the nonunion site during cannulated screw fixation has the advantage of delivering and keeping the biologic material within the fracture site.
O'Malley et al. (2016)	Retrospective 10 professional basketball players with Jones fracture. 7 treated with percutaneous internal fixation with BMAC and 3 treated with open grafting in addition to internal fixation with BMAC.	60 ml of bone marrow aspirate was collected from iliac crest and concentrated using the Magellan system (Arteriocyte, OH). Concentrate injected with fluoroscopy-guidance. Aspirate or concentrate were not analyzed.	Patients were placed in posterior short leg splints immediately after the procedure for 2 weeks of non-weightbearing immobilization. They were then progressed to partial weight bearing with crutches in a removable walking boot for 2 weeks. Patients were then progressed to full weightbearing on crutches while remaining in the walking boot and were allowed to begin water therapy. At the 6-week postoperative point, x-rays and CT scan were taken. The players were allowed to return to play if healing was confirmed radiographically.	All fractures healed at overall average of 7.5 weeks and they were able return to play at 9.8 weeks. Most patients noted to have pes planus and 90% had a bony prominence under the fifth metatarsal styloid. 3 patients experienced refractures.	Patients included in the study were large and possessed a unique foot type that seems to be associated with increased risk of Jones fracture. Authors advocated open bone grafting in addition to internal fixation with BMAC in athletes with a high degree of fifth metatarsal curvature and adductus.

ASIS: Anterior superior iliac spine; BMAC: Bone marrow aspirate concentrate; CT: Computated tomography.

Autologous bone marrow has been used as a percutaneous treatment for managing non-unions and delayed unions after surgical fixation. The first use of autologous bone marrow aspirate injection for nonunion fractures was described by Connolly et al. in 1991. In this study, 20 tibial non-unions were treated with non-concentrated autologous bone marrow injections, resulting in union for 18 out of 20 patients [14]. Subsequently, Hernigou et al. conducted a study where percutaneous intraosseous BMAC injection was performed on 60 tibial non-unions treated with internal fixation, achieving bone union in 53 out of 60 patients. This study underscored the significance of the number and concentration of progenitor cells in BMAC; the concentration and total number of progenitor cells injected into the nonunion sites of the seven cases with failed union were both significantly lower than those with successful union (p = 0.001 and p < 0.01) [15]. In a systematic review conducted in 2017, Imam et al. identified four studies that investigated the use of percutaneous BMAC injection to treat non-unions. Overall, 268 out of 301 fractures (89%) managed with percutaneous BMAC injections demonstrated union, with an average healing time of 2.5 to 8 months and no documentation of adverse events [16]. These studies involved the use of bone marrow aspirate to treat 20 patients with tibial or femoral non-union [17], the use of a combination of BMAC with demineralized bone matrix and/or recombinant human bone morphogenic protein-2 to treat 49 patients with tibial non-union [18], and the use of BMAC at the site of non-unions in 86 ankles in diabetic patients [19]. More recent literature includes the use of BMAC for treating long bones in 93 patients with delayed union or non-union in which union was achieved in all patients within 12 weeks [20], combination of BMAC with bioactive glass in five patients with infected tibial non-union [21], the combination of ORIF and BMAC injection to treat clavicular fractures [22], a case report on the successful BMAC injection outcome used to treat femoral neck nonunion [23], and a case report on the use of a combination of BMAC, platelet-rich plasma (PRP), and platelet lysate in a patient with chronic distal humerus fracture non-union along with an ulnar transection, resulting in resolution of the fracture and improvement in strength [24]. Table 2 summarizes studies that used percutaneous BMAC injection for the treatment of delayed or non-union fractures.

Table 2.

Summary of studies that used percutaneous BMAC injection for the treatment of non-unions or delayed unions.

Study (year)	Study design and patient characteristics	BMAC characteristics and injection technique	Post-injection management	Findings/complications	Conclusions	Ref.
Hernigoue et al. (2006)	Unclear study design 60 tibial non-union that had previously undergone internal fixation were treated with intraosseous BMAC injection.	Average of 612 progenitor cells/cm3 obtained from iliac crest, and average of 2,579 progenitor cells/cm3 in 20 cm3 concentrate. 20 cm3 of BMAC concentrate injected percutaneously with fluoroscopy-guidance.	External fixation was maintained with non-weight bearing status for the first month. After one-month, partial weight bearing was allowed with external fixation in place or with a cast if callus was observed radiographically. After another month, full weight-bearing was allowed. At the end of the month, external fixation or cast is removed once cortical bridging or disappearance of the fracture line is confirmed radiographically.	Bone union achieved in 53/60 (88%) patients at 4 months following the procedure. Complications were not discussed.	Percutaneous BMAC intraosseous injection is an effective and safe method for treatment of atrophic tibial diaphyseal non-union.
Kassem (2013)	Unclear study design 20 delayed or non-union of tibia, femur or ulna that had previously undergone internal fixation treated were treated with intraosseous BMAC injection.	Minimum of 30 ml and up to 80 ml of bone marrow aspirate was collected. The collection was performed without concentrating the aspirate, and BMAC injection was performed with fluoroscopy-guidance. Aspirate was not analyzed.	Not discussed.	Bone union achieved in 19/20 (95%) patients with average healing time of 2.95 months. One patient did not show radiological evidence of new bone formation at the fracture at after 3 months and was considered a failure. There were no complications.	Percutaneous bone marrow aspirate injection (without concentration in this study) appears to be as simple and effective method to accelerate fracture healing for patients with delayed union and nonunion fractures.	[17]
Desai et al. (2015)	Retrospective 49 tibial non-union and delayed union that had previously undergone internal fixation were treated with intraosseous BMAC injection combined with DBM and/or rhBMP-2.	Average of 18 nucleated cells/cm3 in 60 cm3 aspirate collected from iliac crest, and there was average of 101 cells/cm3 in 10 cm3 in the concentrate. 10 cm3 of BMAC with DBM and/or rhBMP-2 was injected with fluoroscopy-guidance.	Non-weight bearing was maintained for 3 weeks. After the 3 weeks, weight bearing was allowed if callus was observed radiographically. Radiographs were repeated every 4 weeks until the fracture healed or nonunion was confirmed.	Bone healing achieved in 79.6% with an average healing time of 4.7 months. No difference in the healing rate between patients with fracture gaps less than or more than 5 mm (p = 0.81). BMAC + rhBMP-2 was linked with lower healing rates compared with BMAC + DBM (p = 0.036). Earlier intervention (within 6 months of fixation) resulted in higher union rates (p = 0.04). There were no complications.	BMAC with DBM and/or rhBMP-2 is an effective treatment for delayed or non-union regardless of the fracture gap size.	[18]
Hernigoue et al. (2015)	Unclear study design Diabetic patients with non-unions in ankle (pilon or malleolar) were given option for either standard iliac crest bone graft or percutaneous BMAC graft. 86 patients were treated with BMAC graft and 86 patients were treated with bone graft.	Average of 150 ml of bone marrow was collected from iliac crest. Average of 61,000 MSCs were injected. Guidance used for injection was not discussed.	Not discussed.	BMAC resulted in healing in 82% compared with 62% in the bone graft group. More complications were observed in the bone graft group compared with BMAC group: infection (17 vs. 1), skin necrosis requiring a flap (11 vs. 1), amputation due to infection (5 vs. 0), mal-union (11 vs. 5) and “occurrence of Charcot neuropathy”. Two patients died as a result of complications in the bone graft group.	Percutaneous BMAC may be preferrable over standard bone graft to avoid risks associated with open surgery and iliac bone grafting.	[19]
Sahu (2018)	Prospective 93 delayed or non-union long bone fractures previously treated surgically or conservatively were treated with BMAC injection.	40–50 ml of bone marrow aspirate was collected from iliac crest and was used without concentrating with “image-intensifier”-guidance. Aspirate was not analyzed. 40–50 ml was used for femur and tibia, 20 ml for humerus and 10 ml for radius and ulna. Some patients had multiple monthly injection, up to four-times.	A compression dressing was given post-operatively. Serial radiographs were taking every 6 weeks until union was observed radiographically.	All fractures were united within 12 weeks. The results were excellent in 69%, good in 19% and poor in 12% of the cases. Most patients had discomfort at donor site for few days, but none had persistent pain. There was no reports of infection, hemorrhage or scar formation.	Percutaneous bone marrow aspirate injection is an effective and safe method for treatment of diaphyseal non-union and delayed union.	[20]
Van Tugt et al. (2021)	Retrospective 5 tibial non-unions previously treated surgically but had become infected were treated with combination of BAG, anti-bacterial bone graft substituted, and BMAC.	Average of 6.2 ml of BMAC collected form iliac crest was implanted along with average of 23 ml of BAG. Aspirate or concentrate were not analyzed. Based on severity of infection and non-union, the treatment was performed as one-stage or two-stage.	Patients started with permissive weight bearing based on guidance of a physical therapist.	All patients showed clinical consolidation and were able to fully bear weight and with successful eradication of infection at the end follow-up. The mean follow-up was 13.6 months. One patient needed additional percutaneous BMAC injection due to “inappropriate healing” at the end of cortical end of the defect. Complete healing of the fracture occurred 4 months later (11 months after 2nd stage). One patient needed surgical intervention due to breakage of the screw.	The early data on combined implantation of BAG and BMAC for the treatment of infected non-union shows promising results for fracture healing and infection eradication.	[21]
Benshabat et al. (2022)	Retrospective 21 clavicular fracture nonunion that were treated with combination of ORIF with BMAC injection.	60 ml of bone marrow aspirate was collected for the iliac crest and concentrated down to 10 ml of BMAC (Terumo Harvest, Tokyo, Japan). Aspirate or concentrate were not analyzed. BMAC was injected into the fracture site that have been surgically exposed.	The patient's arm was held in a sling post-operatively. Activity was limited to passive and active mobilization up to 90o forward flexion and abduction for the first 2 weeks, full range of motion after first checkup at 2 weeks, and strengthening after second follow-up at 8 weeks post-operatively. Gradual return to sports and labor were allowed after clinical and radiographic confirmation of union.	20/21 (95%) patients showed fracture union with a mean time to union of 4.5 months. There were no complications.	ORIF supplemented with BMAC is a safe and highly efficacious treatment for clavicular non-unions.	[22]
Modest et al. (2022)	Case Report 29M with chronic femoral neck nonunion that was previously fixed with three partially threaded cannulated screws and intramedullary nail. Two years post-operatively, patient experienced a pathologic displaced femoral neck fracture and underwent BMAC injection.	100 ml of bone marrow aspirated was collected from ipsilateral iliac crest and was concentrated down to 5 ml. Aspirate or concentrate were not analyzed. BMAC was injected into the fracture site under fluoroscopy-guidance.	The patient was made weightbearing as tolerated post-operatively.	Radiographs and CT scan 12 months post-operatively showed successful union of the fracture. Patient reported complete resolution of his pain. There was no complication reported.	The use of BMAC to augment healing of delayed union or nonunion of the femoral neck, with or without revision internal fixation, is a novel technique with potential benefits.	[23]
Williams et al. (2023)	Case Report A patient with distal humerus fracture non-union along with an ulnar nerve transection that was previously treated with internal fixation who had undergone percutaneous injection consisting of BMAC, PRP and platelet lysate as well as hydrodissection of the ulnar nerve.	80 ml of bone marrow aspirate was collected along bilateral PSIS and was concentrated to produce 1–5 ml of BMAC. The final nucleated cell count was 1.99 billion, which was injected under fluoroscopy-guidance. Ulnar nerve hydrodissection at cubital tunnel was done with mixture of PRP and platelet lysate under ultrasound guidance.	Patient started occupational therapy with pain management using NSAID and corticosteroids for a minimum of six weeks.	Patient demonstrated progressive gains in grip strength and tip pinch. A post-procedural radiograph at 4 months after the procedure showed a healed distal humerus fracture. No complication was observed.	BMAC has shown to be highly successful for treatment of long bone non-union. Addition of PRP and platelet lysates may be beneficial to promote neuroregeneration after a peripheral nerve injury.	[24]

BAG: Bioactive glass; BMAC: Bone marrow aspirate concentrate; DBM: Demineralize1d bone matrix; MSC: Mesenchymal stem cell; NSAID: Non-steroid anti-inflammatory drug; PRP: Platelet rich plasma; PSIS: Posterior superior iliac spine; rhBMP: Recombinant human bone morphogenetic protein.

The exact mechanism of action of BMAC is not fully understood [16]. Similar to PRP, BMAC is an orthobiologic therapy composed of cells, growth factors, and bioactive molecules that may promote musculoskeletal tissue regeneration [25]. A prior study showed that a combination injection of BMAC and PRP improved pain and shoulder function in patients with partial rotator cuff tears, although there was no control group to assess the effect of each component individually [26]. Combination therapy with PRP and BMAC was successfully used percutaneously in a case report to manage a humerus non-union [24]. BMAC may provide direct source of cells as it contains several types of stem cells including MSCs, HSC, endothelial progenitor cells. BMAC also contain various growth factors including PDGF, VEGF, BMP, TGF-beta, IL-8 and IL-1RA. These growth factors are believed to create microenvironment that favor differentiation of stem cells into osteogenic progenitor cells. Furthermore, these stem cells also exert paracrine effect to recruit host cells to the site of injury to promote tissue recovery [4].

The patient in our case report experienced unsuccessful healing despite 8 months of conservative management. Possible factors for the delayed healing include intrinsic factors, such as poor vascularization of the metatarsal head. It is also possible that the patient had poor nutrient absorption due to underlying Crohn's disease. The patient was taking vitamin D and calcium supplement. Prior studies on metatarsal head subchondral fractures suggest that these fractures may primarily occur in patients with underlying conditions predisposing them to insufficiency fractures [27,28].The patient showed resolution of the fifth metatarsal head fracture 12 weeks after receiving a BMAC injection and was able to return to physical activity without experiencing refracture. This suggests that BMAC injection, without surgical fixation, could be a viable option for treating chronic fifth metatarsal head stress fractures that have not responded to conservative management. The current literature on BMAC for chronic bony pathology is limited to a few case reports, and almost exclusively involves BMAC peri-operatively or post-operatively to augment surgical management. In this case, percutaneous intraosseous BMAC injection was successful and may be a safe alternative for some patients, potentially allowing them to avoid surgical fixation. Further studies comparing refracture rates between this approach and surgical methods could offer valuable insights for determining the most appropriate treatment for this rare type of injury.

Financial disclosure

This paper was not funded.

Competing interests disclosure

The first author presented this study as a clinical case at the 2023 annual conference for the American College of Sports Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Ethical conduct of research

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images.