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Hand/Peripheral Nerve: Original Articles

Lipofilling in Osteoarthritis of the Finger Joints: Initial Prospective Long-Term Results

Meyer-Marcotty, Max M.D., Ph.D.; Batsilas, Ioannis M.D.; Sanders, Agnes M.D.; Dahmann, Sonja M.D.; Happe, Caroline M.D.; Herold, Christian M.D., Ph.D.

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Plastic and Reconstructive Surgery: May 2022 - Volume 149 - Issue 5 - p 1139-1145
doi: 10.1097/PRS.0000000000008989
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Abstract

Osteoarthritis in the finger joints is a very common condition experienced by 50 percent of men aged 60 years and older, and by 50 percent of women aged 50 years and older. The main symptoms are restricted function; decreased range of motion; loss of strength, aesthetic impairment; and, above all, pain.

Existing treatment methods include physical measures (e.g., immobilization, physiotherapy, and occupational therapy), drug therapy (e.g., nonsteroidal antirheumatic agents),1 injections of cortisone2 and hyaluronic acid,3 radiation therapy, and surgery.1,2 Most types of surgery on the finger joints, with the exception of joint denervation,4 involve destroying the joint because those sections of the joint that have been altered by the osteoarthritis have to be (partly) resected by means of interpositional arthroplasty5–7 and replaced by alloplastic prosthetic material.8,9 Arthrodesis even requires the destruction of the entire joint. Microsurgical joint replacement with toe joint transfers is another alternative.10 The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early—albeit painful—phases of a condition classified as grade 1 or 2 on the Kellgren-Lawrence scale.

In most cases, surgery is able to achieve a good reduction of the level of pain.1 Complications associated with joint surgery, such as a reduction in strength, prosthetic loosening or dislocation,11 insufficient bony union following arthrodesis of the finger joints, or infections,12 are mentioned in connection with the surgical therapy options. Aftercare following most surgical procedures, involving in some cases several weeks of immobilization and weeks of physiotherapy, can often be very laborious and may result in the patient, depending on his or her profession, being unable to work for a number of weeks.

Against this backdrop, minimally invasive treatment methods that achieve lasting pain relief, coupled with improved strength, mobility, and function, represent an important alternative to conventional therapy options.13–15 Furthermore, all the aforementioned surgical options can still be performed after the transfer of fatty tissue.

Studies based on animal experiments have demonstrated that the mesenchymal stromal cells that are to be found naturally in fatty tissue are capable of regenerating tissue in arthritic joints.16–18 The immunocompetence of the transferred cells has also been already demonstrated, with a reduction in the intraarticular inflammatory processes.17,18 The positive impact can be boosted by the mechanical buffering effect of the intraarticular fluid that is brought in with the mesenchymal stromal cells. The first promising studies of the effectiveness of this type of therapy in humans have also been described.13,19 For the first time within the framework of a prospective study involving a sizable patient cohort, the authors of this article wish to present and discuss the long-term effects of autologous fat transfer to arthritic finger joints with respect to the criteria of force of pinch grip, fist closure, and hand function (Disabilities of the Arm, Shoulder and Hand) and pain.

PATIENTS AND METHODS

Before commencing, the study was presented to the hospital’s ethics committee. No ethical or legal objections to the study were raised. The study encompassed patients for whom conservative treatment to alleviate pain through the use of splints and drug therapy had proven unsuccessful, and who would otherwise have undergone surgery. Only patients were included in the study who had not previously undergone any type of surgery on or received injections into the joints concerned. We strictly followed our patients’ history and treated the painful joint regardless of the radiologic findings. Every treated joint received only a single fat injection.

We provided our patients with detailed information about the possibilities and risks of surgery and of autologous fat transfer to the affected joint. All the patients in this study voluntarily decided to take part in the study and to opt for autologous fat transfer following extensive verbal and written explanations about the aforementioned alternative treatments.

The prospective study of 18 patients (13 female and five male patients and 28 finger joints with osteoarthritis), into whose arthritic joints we injected fatty tissue between December of 2014 and May of 2015, was originally intended to be a pilot study without any specific control group. This is the reason why we did not calculate before the study the number of patients that would be necessary for a statistical analysis. The mean age of the patients was 60.8 years (maximum, 76 years; minimum, 46 years). Based on the Kellgren-Lawrence classification, eight joints showed grade 2, 12 joints showed grade 3, and five joints showed grade 420 (Tables 1 and 2).

Table 1. - Degree of Osteoarthritis
Kellgren-Lawrence Grade No. of Joints MP PIP DIP
2 8 2 4 2
3 12 2 9 1
4 5 5
MP, metacarpophalangeal; PIP, proximal interphalangeal; DIP, distal interphalangeal.

Table 2. - Number and Distribution of the 28 Injected Joints
Joint Digit 1 Digit 2 Digit 3 Digit 4 Digit 5
MP 1 2 3 0 1
PIP 0 5 4 4 5
DIP 0 0 1 0 2
MP, metacarpophalangeal; PIP, proximal interphalangeal; DIP, distal interphalangeal.

Three patients were unable to be included in the subsequent study phases: one multimorbid female patient was not able to come to the follow-up examination, and two patients had moved away without giving a forwarding address and could therefore no longer be contacted. We were able to conduct a follow-up examination of 25 treated joints in the remaining 15 patients (Tables 1 and 2). The operation was carried out under local anaesthesia on the affected joint (2 ml of prilocaine) with a tumescent solution for liposuction in the upper thigh or lateral-gluteal region. The tumescent solution was prepared under sterile conditions [100 ml of sodium chloride solution, 0.6 ml of sodium bicarbonate (8.4%), 0.1 ml of adrenaline, and 5 ml of prilocaine (1%)].21

Subsequently, approximately 50 ml of tumescent solution was distributed in the subcutaneous tissue, using the technique already described.13,22 After an exposure time of 10 minutes, liposuction of approximately 2 × 5 ml of aspirate in two Luer-lock syringes was then performed by means of the classic Coleman technique (Fig. 1).

F1
Fig. 1.:
Coleman technique liposuction from lateral upper thigh using Luer-lock syringe.

Once filled, the syringes were centrifuged at 3000 rpm for a period of 3 minutes in a Laborfuge centrifuge manufactured by Thermo Scientific (Waltham, Mass.). Following centrifugation, the oil and aqueous phases were discarded (Fig. 2).

F2
Fig. 2.:
Following centrifugation, the aspirate can be seen to have separated into an oil phase (top phase), a fat phase (in the center below the oil phase), and a reddish aqueous phase (below the fat phase).

As a matter of principle, we do not undertake any further treatment of the cells using enzymatic reagents. A volume of 0.5 to 1 ml of fatty tissue was injected into each joint under sterile conditions in the operating room. Light manual axial traction of the finger proved helpful in opening the joint space when introducing the needle (Fig. 3).

F3
Fig. 3.:
Intraoperative image of fat injection into a distal interphalangeal joint with the intraarticular needle.

We injected as much of the fatty tissue as could be injected easily into the joint depending on the size of each injected joint [larger metacarpophalangeal joints received a greater volume of fatty tissue (i.e., 1 ml) than smaller distal interphalangeal joints (i.e., 0.5 ml)]. The fat was injected at once under radiographic control, so no second injection was attempted. For injection, we used an 18-gauge needle on a 2-ml Luer-lock syringe.

Subsequently, a metacarpal splint enclosing the finger was fitted for a period of 7 days. Then, everyday activities were resumed, with the patient attempting to avoid putting unnecessary strain on the treated hand. None of the patients required any physiotherapy. World Health Organization step 1 pain medications were prescribed in the first week after surgery and taken as required.

Before surgery, and at the follow-up appointment, hand function was evaluated using the German version of the Disabilities of the Arm, Shoulder and Hand questionnaire,23 where a score of 0 meant unrestricted hand function and a score of 100 meant an unusable hand. Pain was classified according to a visual analogue pain scale, where 0 = no pain and 10 = severest unimaginable pain. To facilitate this, we calculated an average from “pain at rest” and “pain at stress” for each individual patient and used this for our further evaluation.

Furthermore, the development of the patient’s hand strength was determined using a Jamar dynamometer and pinch strength measurement. Both the force of pinch grip and fist closure were determined as the mean value calculated from at least three measurements.

The primary statistical analysis was performed with the aid of a Wilcoxon signed rank test. The calculations were carried out by using IBM SPSS Version 25 (IBM Corp., Armonk, N.Y.). A value of p < 0.05 was regarded as statistically significant.

A post hoc analysis was performed for the data with a value of p > 0.05 using G*Power. G*Power is a tool to compute statistical power analyses for many different tests.

RESULTS

We were able to conduct a follow-up examination of 25 joints for this long-term assessment. In our patients, we assessed strength (subdivided into force of pinch grip and fist closure), hand function (ascertained using a German translation of the Disabilities of the Arm, Shoulder and Hand questionnaire), and pain levels, before and on average 44 months (a minimum of 37 and a maximum of 50 months) after surgery. The power of the tests with values of p > 0.05 were 42.8 percent (Disabilities of the Arm, Shoulder and Hand) and 46.7 percent (force of fist closure), indicating that larger sample sizes will be needed to identify significant differences between before-and-after values.

Strength

Force of Pinch Grip

The force of pinch grip rose highly significantly from a presurgical median of 2.00 kg (range, 0.00 to 11.00 kg) to 4.30 kg (range, 2.00 to 12.00 kg) (p < 0.001) (Fig. 4).

F4
Fig. 4.:
Development of the force of pinch grip during the follow-up examination period (in kilograms).

It is important to know which joints were injected in the patients whose pinch strength improved. To answer that question, we divided our 25 joints into two groups: group A with fat injection into digits 1 to 3 (13 joints), and group B with fat injection into digits 4 and 5 (12 joints). We chose this division because the pinch grip is mainly done with digits 1 to 3. As one can see according to the Wilcoxon signed rank test, the force of pinch grip improved in both groups highly significantly from preoperatively to follow-up in a very similar way (Table 3).

Table 3. - Correlation of the Development of the Force of Pinch Grip to the Injected Joints
Group A (Digits 1–3) Group B (Digits 4 and 5)
Preoperatively Follow-Up Preoperatively Follow-Up
No. 13 13 12 12
Minimum, kg 0.00 2.00 0.00 2.00
Median, kg 2.00 4.00 3.00 4.67
Maximum, kg 11.00 12.00 5.00 6.00
p <0.001 <0.001

Force of Fist Closure

The force of fist closure rose from a presurgical median of 15.00 kg (range, 2.00 to 44.00 kg) to 18.00 kg (range, 3.78 to 42.00 kg) (p = 0.082) (Fig. 5).

F5
Fig. 5.:
Development of the force of fist closure during the follow-up examination period (in kilograms).

Hand Function According to the Disabilities of the Arm, Shoulder and Hand Questionnaire

During the follow-up examination period, hand function was found to improve nonsignificantly from a presurgical median of 50 (range, 3 to 72) to 25 (range, 0 to 85) (p = 0.129) (Fig. 6).

F6
Fig. 6.:
Development of hand function based on the recorded Disabilities of the Arm, Shoulder and Hand (DASH) scores during the follow-up examination period.

Pain According to the Visual Analogue Scale

The level of pain experienced shows a highly significant clear improvement during the follow-up examination period from a presurgical median of 6.0 (range, 1.0 to 10.0) to 0.5 (range, 0.0 to 6.5) (p < 0.001) (Fig. 7). Those patients who underwent the follow-up examination did not show any infections or other complications.

F7
Fig. 7.:
Development of pain and visual analogue scale (VAS) scores during the follow-up examination period.

DISCUSSION

The present study demonstrates for the first time within the framework of a prospective study that a positive long-term effect can be achieved by transferring autologous fatty tissue to arthritic finger joints in patients, with a significant improvement in force of pinch grip and pain levels. Force of fist closure and Disabilities of the Arm, Shoulder and Hand scores also improved over the time of follow-up but were not significant. Although Damia et al. describe in a recently published review a positive effect of adipose-derived stromal cells in the treatment of osteoarthritis in humans, the limited evidence and lack of long-term results are also mentioned.14

The good short-term results achieved by Herold et al.13,22 and also by Haas et al. in 202015 with respect to the saddle joints were also confirmed in our study on the small finger joints over a long-term period. This was particularly evident in a significant pain reduction and an improvement in strength and hand function (i.e., Disabilities of the Arm, Shoulder and Hand score). We believe that, for our patients, the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect.

It has been demonstrated in various studies that a very high concentration of pluripotent mesenchymal stromal cells is present in fatty tissue, and that these pluripotent cells can also transform into local tissue.24,25 Furthermore, animal experiments have shown that transplanting stem cells from fatty tissue to arthritic joints can have a positive effect.16 Wu et al. have demonstrated that, under experimental conditions, cartilage regeneration is stimulated by these mesenchymal stromal cells.26 In contrast, chondrocytes can promote the transformation of mesenchymal stromal cells, giving rise to an additional potentially therapeutic effect in the treatment of arthritic joints.26 Furthermore, the cells transplanted with the fatty tissue are thought to have immunocompetence that is capable of resisting inflammatory processes in the joint.17,18 Last but not least, a mechanical effect can also be expected because of the viscoelastic properties of the transplanted tissue, similar to those achieved with intraarticular injections of hyaluronic acid.

It is still unclear precisely how osteoarthritis therapy using mesenchymal stromal cells from fatty tissue functions. On the basis of the long-term results we have here, we postulate that, on the one hand, the mechanical properties of the transplanted tissue, as injected viscous fluid, have a short-term positive effect. On the other hand, the immunocompetence of the transferred mesenchymal stromal cells is presumably also responsible for the long-lasting positive effect. It is not possible on the basis of our data to determine the extent to which the automatically co-transplanted mesenchymal stromal cells from the fatty tissue that contains them also transform into cartilage cells in arthritic human joints. For ethical reasons it would certainly be difficult during a study to obtain human presurgical and postsurgical biopsy specimens from the arthritic joint cartilage for the purposes of histologic examination.

In their review, Delanois et al. have compared various biological methods (platelet-rich plasma, bone marrow–derived stromal cells, adipose-derived stromal cells, and adipose mesenchymal stromal cells) of treating osteoarthritis of the knee. They conclude that although good initial results can be achieved for patients with all the methods they studied, many questions remain unanswered, and no long-term results have been described for any of these treatment methods. Despite the limitations identified in the studies, there does appear to be evidence supporting the use of the various biological methods to treat osteoarthritis of the knee.27 As Chiari et al. note, some unresolved issues remain regarding the ideal fat removal site.19 We remove the fat from the upper thigh or lateral-gluteal region, but not from the abdominal fat, as in this case we would have to inform our patients about the potential, albeit unlikely, possibility of a bowel injury, with the consequent need for a colostomy.

During the course of osteoarthritis treatment by means of lipofilling, we do not add reagents or agents to the cells as a matter of principle because the effect of such additions (e.g., enzymes) on the cells has not been sufficiently studied, and cells whose composition has been changed are subject in Germany to the German Medicinal Products Act because they are then classified as advanced therapy medicinal products.28,29 Furthermore, it will be very difficult to determine in the analysis which procedure is responsible for the achieved effect. This entails the risk of polypragmasia.

Intraarticular injections of cortisone or hyaluronic acid represent alternatives to the methods presented here. However, no lasting effect has been demonstrated so far for either procedure.3,30 Furthermore, local damage caused by repeated cortisone injections should not be underestimated.31,32 Insufficient antiseptic procedures in particular are often cited as the cause of complications. We always perform the autologous fat transfer in the operating theatre under sterile conditions, and we have had no infections. Good results in the treatment of finger joint osteoarthritis have been achieved by various surgical methods.1 However, these surgical procedures usually result in destruction of the joint; they are much more invasive than fat transfer; and they entail in some cases very long immobilization and postsurgical physiotherapy periods. Because conventional treatment methods remain an option even after fat transfer, we regard fat transfer to be a safe and minimally invasive way of expanding the spectrum of possible treatments.

Limitations of our study are the fact that we have no control group. Because the data on intraarticular injection of cortisone into osteoarthritic interphalangeal joints are very limited with only short-term benefits (6 to 12 weeks), we did not choose that method as a control versus intraarticular fat transfer in our long-term follow-up. Many authors reported good short-term results after an injection of cortisone, but there are no long-term results in the literature, at least to our knowledge.30,33–35 Therefore, we did not see a cortisone injection as a valid control group for our long-term study. Further work with even larger patient cohorts should be performed.

CONCLUSIONS

Even after a follow-up examination period of 44 months, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe, and promising alternative to conventional surgical techniques aimed at alleviating arthritic complaints, and one that among other things entails a highly significant improvement in postsurgical pain levels. Because this method preserves the joint, conventional resection surgery remains a later option. Further long-term follow-up studies of even larger patient cohorts would be needed to further corroborate these initial positive findings.

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