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. 2019 Mar 27;16(4):916–924. doi: 10.1111/iwj.13119

Autologous lipotransfer for bone defects secondary to osteomyelitis: A report of a novel method and systematic review of the literature

Katharina B Reinisch 1, Grzegorz Zuk 1, Dimitri A Raptis 2, Marco Bueter 2, Merlin Guggenheim 3, Tilman Stasch 4, Adrian F Palma 5,✉
PMCID: PMC7948694  PMID: 30916475

Abstract

Autologous bone grafting is the gold standard in patients with bone defects but is associated with significant pain and donor site morbidity. Autologous lipotransfer (fat grafting or lipofilling) has become very popular in the therapy of chronic wounds. Mesenchymal stem cells from adipose tissue are known for their regenerative, reparative, and immunomodulatory effects. This case study and review evaluates the use of autologous lipotransfer for chronic osteomyelitis in a 26‐year‐old patient. A 26‐year‐old female suffering from chronic tibial osteomyelitis was initially treated with surgical debridement and antibiotics followed by lipoharvest and autologous lipofilling. MRI and computed tomography scans were performed at 2 and 6 weeks and 6 months postoperatively. A formal systematic review of clinical trials investigating autologous lipotransfer for osteomyelitis was conducted. The patient remained asymptomatic without recurrence, and the bone defect cavity showed vascularised adipose tissue after 6 weeks, with early signs of osteogenesis. The highest foot and ankle disability index was 100. The systematic review identified 266 studies after duplicates were removed. After screening for eligibility, seven manuscripts were further assessed, with none meeting the inclusion criteria. This is the first study to report the successful use of autologous lipotransfer with early signs of osteogenesis in a patient suffering from chronic osteomyelitis. Autologous lipotransfer is relatively simple, safe, and minimally invasive, making it a potential alternative to current treatments. Further research is required to assess the safety, feasibility, and efficacy of autologous fat grafting and the mechanism of osteogenesis.

Keywords: autologous fat grafting, bone defects, lipofilling, osteomyelitis

1. INTRODUCTION

Osteomyelitis is a pyogenic infection and inflammation of bone, which remains challenging for both patients and physicians. Staphylococcus aureus is the most common organism isolated from all forms of osteomyelitis. Acute haematogenous osteomyelitis is most common in children, while in adulthood, osteomyelitis often occurs after trauma exposes the bone to local infection. Osteomyelitis usually presents as an acute infection, but it may evolve into a chronic condition. Treatment generally involves evaluation; staging; determination of microbial aetiology and susceptibilities; antimicrobial therapy; and, if necessary, debridement, dead‐space management, and bone stabilisation.1, 2

Dead‐space management is often difficult in osteomyelitis. While dead‐space management is not an issue in the absence of infection, synthetic spacers should be used with caution in the context of acute infection. Bone allografts may be rejected secondary to infection. Furthermore, bone allografts harvested from the iliac crest are related to donor site morbidity.3 In contrast, lipoharvest is a simple, quick, and gentle alternative providing fat as a dead‐space filler. We know that adipose‐derived stem cells are able to differentiate into various cells, including osteoblasts.4, 5 The use of autologous fat grafts for dead‐space management in osteomyelitis was first described by Green.6

The purpose of this study was 2‐fold: (a) to introduce a novel method of autologous lipotransfer for bone defects secondary to osteomyelitis and (b) to perform a systematic review of the literature assessing potential complications related to lipofilling, as well as the feasibility and efficacy of autologous fat transfer for osteomyelitis.

2. CASE REPORT

A 26‐year‐old woman suffered a snowboard accident when she was 13 years old, resulting in bilateral distal lower‐extremity fractures. The fractures were treated with closed reduction and external fixation, with an uneventful postoperative course. Thirteen years later, she was admitted to the internal emergency department with suspected ankle arthritis because of pain and swelling of her left ankle, an elevated C‐reactive protein, malaise, and stable vital parameters. Planar X‐rays (Figure 1) showed an osteolytic lesion of the left distal tibia, at the former location of an external fixation pin, with significant swelling of the surrounding soft tissue. Subsequent computed tomography (CT) (Figure 2) and magnetic resonance imaging (MRI) scans (Figure 3) showed a 25 × 18 × 16 mm lesion suggestive of osteomyelitis.

Figure 1.

Figure 1

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Initial x‐ray

Figure 2.

Figure 2

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Initial CT scan

Figure 3.

Figure 3

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Initial MRI scan

Surgical management, performed 6 days after presentation, consisted of opening the bone cavity via the former ventral cortical pinhole and evacuating pus, followed by biopsy, debridement, and irrigation. A gentamycin‐containing bead was used to deliver local antibiotics and for temporary dead‐space management. We also initiated an empirical antibiotic therapy with amoxicillin/clavulanic acid 4 × 2.2 g/24 hours i.v. on the day of the operation. A few days later, the presence of S. aureus infection was confirmed.

A second debridement and replacement of the gentamycin bead was carried out on postoperative day 15, and a negative biopsy result was observed on postoperative day 17. Antibiotic therapy was switched to daptomycin 500 mg/24 hours i.v. for outpatient management 19 days after the first operation; this continued for another 3 weeks. Several potential dead‐space management strategies were discussed within our department.

Although autologous bone grafting is the gold standard, donor site morbidity and potential complications, such as persistent pain and fracture of the anterior superior iliac spine, remain problems.7 Furthermore, the patient required immediate load‐bearing capacity because of her role as a mother. We considered bone healing without dead‐space management; however, the literature on healing by secondary intention and closed irrigation systems was inadequate.8 Synthetic bone grafts were not considered because of the risk of re‐infection. Similarly, bone flaps were impractical because of increased complexity and the nature of the wound.8

The third debridement and irrigation of the bone defect, along with autologous lipotransfer, was performed 33 days after the first operative treatment. The autologous harvesting of adipose tissue was performed using water jet‐assisted abdominal liposuction (WAL; Body‐Jet, Human Med AG, Schwerin, Germany) to preserve cell viability. With WAL, the fat is detached from the tissue structure in a gentler fashion than with conventional liposuction. Adipose tissue was collected in the LipoCollector (Human Med AG), where it was continuously washed in sterile saline solution (0.9% NaCl, Fresenius Kabi, Bad Homburg, Germany) and separated from blood cells and oil without centrifugation. The resulting lipoaspirate was then injected in 20 mL portions into the bone cavity measuring about 7 cm3 and into the soft tissue. The bone cavity remained open to the surrounding tissues, but the subcutaneous tissue and 4 cm skin incision were closed with Vicryl 3‐0 and Ethilon 3‐0 sutures from Ethicon (Somerville, Massachusetts), respectively. Mepitel by Mölnlycke Health Care (Gothenburg, Sweden) and pressure‐free gauze bandages were applied, and the patient was maintained on bed rest for 5 days.

Full weight bearing was achieved 2 weeks postoperatively. The highest foot and ankle disability index was 100 (highest score). There was no haematoma or swelling of the abdomen post‐lipoharvesting. MRI scans were performed 2 and 6 weeks postoperatively (Figures 4 and 5). The radiology report showed vascularisation of the adipose tissue and a reduction in osseous oedema and the cavity itself. The patient described reduced pain and was satisfied with both the results of the ankle and the abdomen.

Figure 4.

Figure 4

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MRI scan 2 weeks after surgery

Figure 5.

Figure 5

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MRI scan 6 weeks after surgery

Further follow up consisted of combined MRI and CT scans after 6 months (Figures 6, 7, 8). These exams confirmed marginal ossification, granulation tissue in the centre, and no signs of recurrence. The patient remained asymptomatic and could perform her daily routines without difficulty. A detailed chronology is provided in Figure 9.

Figure 6.

Figure 6

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MRI scan 6 months after surgery

Figure 7.

Figure 7

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CT scan 6 months after surgery

Figure 8.

Figure 8

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Spectral CT scan 6 months after surgery

Figure 9.

Figure 9

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Detailed chronology of the treatment course

This case was performed in accordance with all ethical standards established by the 2000 Declaration of Helsinki9 and the 2008 Declaration of Istanbul.10 Study approval was provided by the clinical review board. The patient gave written informed consent prior to study inclusion, and this is available upon request.

3. SYSTEMATIC REVIEW

3.1. Methods

A systematic review was performed according to the PRISMA 2009 checklist and former systematic reviews.11, 12

3.2. Protocol and registration

The systematic review protocol was registered in advance at the PROSPERO international registry of systematic reviews (CRD42017065517).13

3.3. Eligibility criteria

All published case reports, case series, randomised controlled trials, prospective and retrospective comparative cohort studies, and case‐control studies that evaluated autologous lipotransfer for osteomyelitis were considered. No language or year limitations were applied. Animal studies, in vitro studies, and studies reporting synthetic or both autologous bone grafting and pedicled or free fat transfer were excluded.

3.4. Information sources

The MEDLINE/PubMed database, Cochrane Library, Embase, and SCOPUS were searched until 1 December 2016.

3.5. Search

We searched for different keywords, including osteomyelitis, adipose tissue, lipofilling, and combinations thereof. The detailed search strategy is presented in Figure 10.

Figure 10.

Figure 10

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Study selection

3.6. Study selection

A systematic review of the literature was performed to identify all studies evaluating autologous fat transfer for osteomyelitis. In addition, reference lists of relevant articles were screened to capture any potential abstracts not identified by the literature search.

3.7. Data collection process

Titles and abstracts were used to identify suitable articles. Two independent reviewers (A.F.P. and K.B.R.) screened the records. Full texts were reviewed where suitable; however, no data extraction was necessary.

3.8. Risk of bias in individual studies

The GRADE System was used to assess final recommendations (Grading of Recommendations Assessment, Development and Evaluation, http://www.gradeworkinggroup.org/intro.htm).14 This metric evaluates the quality (level) of evidence and the strength of the recommendations.

3.9. Synthesis of results

A narrative synthesis was planned. Furthermore, a quantitative synthesis (meta‐analysis) was intended for sufficiently homogenous studies.

3.10. Outcomes of interest

The primary outcome measure was complications related to lipofilling for osteomyelitis. Secondary outcomes were graft survival and surgical feasibility.

4. RESULTS

4.1. Study selection

A total of 343 articles and abstracts were identified, with 266 duplicates removed. After screening for the eligibility criteria, seven were assessed further, and one duplicate was removed (Figure 11).

Figure 11.

Figure 11

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Standard operating procedure

One older study described the transplantation of free fat to growth plates of the femur and tibia. The patients suffered partial closure of the growth plates following fracture or septic osteomyelitis.15 The study did not report on bone defects secondary to osteomyelitis itself.

A case report from Turkey described a lesion in the jaw with a recurrent keratocystic odontogenic tumour, a tumour that suggests true neoplastic potential. It was surgically enucleated, and the dead space was successfully filled with autologous fat harvested from the abdomen. The patient had an uneventful course without complications or local recurrence.16

Djalilian et al reported five patients with large skull base defects because of complex infections (mainly meningitis but not osteomyelitis). Free tissue transfer, such as myofascial and muscle free flaps, was successfully used for dead‐space management after debridement.17

Kulakov et al presented a case report of eight patients with pronounced deficits of the maxillary and mandibular bone tissue. They postulated that autologous bone grafting would be the gold standard but it would be difficult to achieve a sufficient amount of automaterial. Instead, they processed adipose‐derived stromal cells (ADSCs)/multi‐potent mesenchymal stromal cells in vitro that were pre‐differentiated towards osteogenic lineage on biocompatible materials.

They then transplanted this biodegradable tissue‐engineering construct layered with platelet‐rich plasma. After 3 months, young bone tissue could be demonstrated on histological examination and CT scan.18

A recent review presented novel methods of the nanotechnological field that carry more efficient and improved surgical and non‐surgical approaches to complex tissue reconstructions, including bone defects. Non‐surgical approaches mean implantable devices for the delivery of therapeutic agents to the bone. None of the reviewed studies described autologous fat grafting as a simple treatment option for bone defects secondary to osteomyelitis as this is not part of the nanotechnological field.19

Guerrissi et al described successful lipofilling of a dermal ulcer secondary to osteomyelitis but not the bone defect itself.20

5. DISCUSSION

This is the first case of successful autologous fat grafting for bone defects secondary to osteomyelitis, as confirmed by the systematic review. The case refers to a young female patient suffering from acute‐on‐chronic osteomyelitis following trauma and surgery 13 years ago. After successful initial management, including debridement, sampling, and both local and systemic antibiotic therapy, dead‐space management was discussed. We excluded autologous bone grafting because of known donor site morbidity and potential complications, such as persistent pain or fracture of the anterior superior iliac spine,7 despite knowing that this method is the current gold standard for dead‐space management. Therefore, we performed autologous lipofilling using WAL. The sterile lipoaspirate used in this study can be considered macrofat, such as that used in the BEAULI (Berlin autologous lipotransplantation) protocol, where the individual fat particles measured between 1 and 3 mm.21We also developed a relevant standard operating procedure available in Figure 11.

Osteomyelitis is a challenging condition for physicians. There are two major classification schemes. The Lew and Waldvogel classification relates to aetiology and differentiates between haematogenous osteomyelitis, contiguous osteomyelitis from trauma or surgery, and osteomyelitis because of vascular insufficiency such as that seen in diabetes mellitus.22 The Cierny and Mader classification provides guidance for management, is divided by anatomical stages, and is placed in the setting of host health status.23 Microbial factors play an important role in the pathogenesis of osteomyelitis. S. aureus is the most common isolate, typically originating from distant foci of infection such as skin abscesses, endocarditis, vascular catheters, or i.v. drug use.1 The source of infection in this case is unknown; the patient presented in good health with no fever, chills, or obvious or expired (especially dental) infections.

Treatment of osteomyelitis must prevent the spread of disease, control the damage, and repair the damage already caused. Close co‐ordination between the surgeon and infectious disease specialist is essential. Soft‐tissue defects can heal primarily via shrinkage, but bone is limited in its capacity to heal and often requires secondary filling to facilitate defect closure. The literature suggests that autologous bone grafting is the gold standard for dead space and defect management in chronic osteomyelitis.24 However, there are studies demonstrating considerable morbidity following anterior iliac crest bone harvest. The complications of the anterior iliac approach can include prolonged postoperative pain, altered gait, sensory nerve damage, poor scar placement and altered bone contour, delayed healing, herniation of abdominal contents, clicking during walking, ilium fracture, peritonitis, excessive blood loss, and rarely retroperitoneal haematoma.25 Free and pedicled fat transplants have also been described and are well established in the management of bone defects in cranio‐maxillofacial surgery; however, these procedures are resource intensive, expensive, and limited to specialised centres.17, 26 In autologous fat transfer, the possible complications appear to be minimal and related to the liposuction technique (like bruising, swelling, haematoma formation, paraesthesia or donor site pain, infection, hypertrophic scarring, contour irregularities, and damage to the underlying structures, eg, because of the intra‐peritoneal or intramuscular penetration of the cannula if fat is harvested from the abdomen).27 Our case shows the potential effects of autologous fat transfer on bone healing compared with autologous bone grafting. Importantly, there was no complications or known morbidity, and the procedure was easy to perform.

The lipoaspirate is characterised by macrofat. This contains adipocytes and fills up large defect sites. Microfat also contains adipocytes and is used for more sensitive areas with small cannulas. Nanofat is an emulsion of destroyed adipocytes that can be used for joint lipofilling or subcutaneous injections.4, 28 Nevertheless, it has been shown that no significant difference exists in the quantity of mesenchymal stromal cells (MSCs), nor the capacity for differentiation, between these fat types.29

In 1998, Coleman modernised the use of autologous fat grafting when he described the three steps of fat extraction, preparation via centrifugation, and re‐implantation of the pure fat.30 As described above, we used the LipoCollector rather than centrifugation to prevent cell destruction and to minimise manipulation of the lipoaspirate.

Chronic wounds and osteomyelitis are challenging conditions in surgery, with long‐term therapy potentially leading to amputation. Autologous fat transfer has been successfully used in patients suffering from chronic wounds.31 Stasch et al have shown that most patients with chronic wounds treated with DEbridement and Autologous LipoTransfer (DEALT method) experienced complete wound healing with stable soft tissues. Wounds healed with no recurrence, and no complications were noted.31 The authors attributed the positive effects of fat grafting in the chronic wound environment to the direct and paracrine effects of ADSCs on the local tissue environment.

The positive effects of adipose tissue have also been described in patients suffering from scars,32 burns,33 and chronic wounds.34 Furthermore, lipofilling has been applied in the treatment of decubital ulcers.35 Beyond reconstructive aspects, fat grafting is also used in aesthetic surgery,36 as a filler alternative, and in breast augmentation.37, 38 Fat grafting can be combined with silicone implants in patients with scant soft tissues but is also used as a rescue procedure after capsular contracture of breast implants.39 It has advantages for breast reconstruction after cancer but is limited by the need for multiple sessions and limited harvesting areas. Another treatment option is autologous lipotransfer in joints because of painful arthrosis. This can lead to reduced pain and improved strength.4 Facial re‐contouring is another aesthetic application of fat grafting.40

Animal models have shown neosynthesis of collagen tissue after transplantation of human fat.41 An in vitro study showed that the adipogenic capacity of fat grafts is comparable between rabbits, rats, and humans,42 while human adipose‐derived mesenchymal stem cells have better osteogenic potential than rats43 and rabbits.42 It appears that adipose‐derived stem cells play a leading role in this potential. The vascular stromal fraction of the adipose tissue contains multi‐potent MSCs, with an unlimited capacity for self‐renewal. Such cells can potentially differentiate into multiple distinct cell lineages, including chondrogenic, adipogenic, and osteogenic lineages.44 Therefore, they have great promise for tissue engineering.5

The expression of growth factors, as well as adipokines such as leptin45 and adiponectin,46 also stimulates fusion and differentiation of tissue.47These factors target the wound site via paracrine mechanisms and improve wound healing with fusion and differentiation into keratinocytes or fibroblasts, among other roles.48

MSCs were initially discovered in bone marrow.49 Zuk et al described in 2001 the vast amounts of mesenchymal stem cells present in human adipose tissue.50 Several studies have compared the osteogenic potential of human bone marrow‐derived stem cells (BMSCs) and ADSCs in vitro and in vivo. BMSCs have a greater osteogenic potential, while ADSCs are more angio‐inductive; however, there is no absolute consensus.51 In comparison with bone marrow, harvesting adipose tissue and ADSCs via liposuction is fast, minimally invasive, and has low donor morbidity.52

We hypothesised that the mechanism of new bone formation was because of osteogenic differentiation of ADSCs. In keeping with observations by Stasch et al, we did not attempt to transfer isolated stem cells. This is a time‐intensive, complex, costly process compared with simple fat transfer and requires special regulatory approvals.31 Fat transfer may be more effective than stem cells alone because fat tissue contains other compounds necessary to fully repair bone defects. Harvested fat tissue forms a physical scaffold within the bone defect and soft tissue, which may also stimulate new cells to migrate and grow. Furthermore, cultivation of stem cell suspensions and stem cell enhancement is regulated in Switzerland and many other countries.53 Therefore, a study protocol based on stem cell isolation was not suitable.54 Harvesting small quantities of plain fat tissue is simple, cost effective, fast, and minimally invasive. Based on our results, enhancing wound healing with additional platelet‐rich plasma, as described by Cervelli et al, is not necessary but may be investigated in future trials.55

The study has several limitations. First, this is only a single case report and cannot be generalised as a result. We plan on reporting on a bigger sample size in the future. Nevertheless, our patient had an uneventful course with no signs of recurrence or complications. Second, time was not controlled. One can argue that the defect would have healed spontaneously without lipofilling. However, it is well known that large bone defects may not exhibit any signs of osteogenesis or granulation tissue after considerable follow‐up time.8 Third, the literature search may be incomplete. However, we performed a well‐designed literature search across several databases with no year or language limitations. Fourth, we did not perform a biopsy postoperatively to histologically confirm bone reconstruction because of ethical and patient concerns. Finally, this is the first study to report on autologous fat grafting in bone defects secondary to osteomyelitis and is susceptible to unknown confounders given the novel approach implemented.

In conclusion, lipofilling is an effective, feasible, safe, and economical treatment alternative for bone defects secondary to osteomyelitis in select cases. Stem cell isolation is not mandatory, and this reduces costs and makes our procedure feasible in many countries where stem cell enrichment is subject to regulation. No complications with harvesting or transfer of fat were observed, and the patient showed an optimal outcome. While the mechanism of defect repair is not fully understood, and further clinical studies are required, we emphasise the value of lipofilling for the treatment of osteomyelitis and bone defects in general. Subsequent studies should validate these findings in cell and animal models before progressing to large, randomised trials.

Reinisch KB, Zuk G, Raptis DA, et al. Autologous lipotransfer for bone defects secondary to osteomyelitis: A report of a novel method and systematic review of the literature. Int Wound J. 2019;16:916–924. 10.1111/iwj.13119

This article was presented at the 104th Congress of the Swiss Surgical Society, Bern, Switzerland, 31 May 2017 and 47th World Congress of Surgery, Basel, Switzerland, 14 August 2017.

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