Outcomes of Charcot Arthropathy Limb Salvage with Patient-Specific 3D-Printed Cage and Dynamic Hindfoot Fusion Nail Combination Fixation

doi:10.21203/rs.3.rs-4096092/v1

Background

The challenge of surgical treatment of hindfoot collapse can be exacerbated by host conditions that may limit healing potential and increase the risk of infection. Many patients with neuropathy, Charcot joint, or end-stage arthritis that undergo tibiotalocalcaneal (TTC) fusion with bulk allograft progress to nonunion and often require amputation. 3D-printed titanium implants provide benefits that may improve outcomes of limb salvage within this population, but long-term outcomes of these implants have not yet been reported, given their relatively recent development. This study reports mid-term outcomes of patients with Charcot arthropathy or end-stage arthritis who received 3D-printed titanium cage and dynamic hindfoot fusion nail combination fixation for limb salvage.

Methods

This study was a retrospective review of consecutive patients who underwent hindfoot arthrodesis with a combination of patient-specific 3D-printed titanium cage and dynamic hindfoot fusion nail by a single surgeon at a single institution. The primary outcome was to establish the safety of the 3D-printed cage in a medically complicated population. Medical records were reviewed for adverse events, including subsequent surgical intervention and implant survivorship. The secondary outcome was to evaluate the efficacy of the 3D-printed cage, as evaluated by patient-reported pre- and post-operative 11-point Numeric Rating Scale (NRS) pain score, ambulation status, and satisfaction. Deformity correction was evaluated by radiograph. Descriptive statistics were calculated, and a Kaplan-Meier curve of all-cause reoperation was produced.

Results

This study evaluated 13 cases with at least one year follow-up. Mean follow-up was 3.72 years (range 2.67–4.60 years). As of the most recent follow-up, 11 of 13 cages remain implanted, with two cages having been explanted in the setting of amputations indicated by conditions unrelated to the cage itself. Patients reported a mean pre-operative NRS pain of 6.6 ± 2.9 points. At the last follow-up, mean NRS pain was 2.0 ± 1.7 points. Pre-operatively, six of 13 patients reported the ability to ambulate independently without an assistive device. Post-operatively, 11 of 13 patients were able to ambulate independently.

Conclusion

This study reports mid-term outcomes of TTC arthrodesis with a patient-specific 3D-printed titanium cage and dynamic intramedullary nail in patients with Charcot arthropathy or non-traumatic arthritis. The results demonstrate no implant-related complications and promising outcomes in terms of fusion, deformity correction, and patient satisfaction, which are especially remarkable in the setting of Charcot arthropathy. While this data is promising as a technique for limb salvage in this patient population, further experimental studies are required to demonstrate superiority.

Level of Evidence: Level IV

Orthopedic Surgery

Charcot arthropathy

limb salvage

custom implant

patient-specific

3D-printed

cage

dynamic

hindfoot fusion

Charcot arthropathy results from a progressive systemic disease that causes poor micro-circulation and neuropathy. These host conditions complicate the surgical management of Charcot arthropathy as poor circulation and neuropathy limit healing and bone growth potential and increase the risk of infection.^1,2 As a result, surgery to address hindfoot collapse in the setting of Charcot arthropathy, most commonly tibiotalocalcaneal (TTC) fusion with bulk femoral head allograft, has demonstrated limited success.³ Many patients fail to achieve TTC fusion, necessitating further surgery, which may include prolonged external fixation requiring multiple surgeries or, ultimately, amputation.⁴ A study of 23 patients who underwent TTC fusion with bulk femoral head allograft reported a fusion rate of 63%.³ A separate study of the same procedure in 32 patients reported an overall fusion rate of 50% and 0% fusion among the subgroup of nine patients with diabetes.⁵ Even in cases where fusion is achieved, graft collapse may contribute to a loss of deformity correction.^5,6

Early studies have shown that 3D-printed titanium implants offer benefits that may promote fusion in the setting of challenging systemic disease.⁷ A non-biologic implant is beneficial as it obviates the risk of donor site morbidity, graft collapse, and immune response. There is also evidence to suggest a decreased risk of infection.^7,8 3D-printed titanium implants are typically designed with a porous structure that also enables packing with biologic agents (i.e., auto or allograft) that promote osseointegration and are designed to accommodate other implants such as intramedullary nails providing fixation.^9,10 3D-printed titanium implants may also be produced with patient-specific dimensions, which can improve fit, simplify surgical technique, and reduce operative time.¹⁰ These implants may also provide durable, large deformity correction in a single-stage procedure. Single-stage surgery is desirable due to the avoidance of risks inherent to multiple surgeries, such as increased risk of infection or anesthesia-related complications, and due to faster rehabilitation and return to work, which may reduce financial strain and improve quality of life.

While there have been increasing reports of 3D-printed implants for orthopaedic indications, the use of these implants in the setting of systemic disease and for the treatment of particularly challenging conditions such as Charcot arthropathy is understudied. Given the inadequacy of current treatment options for these patients, it is critical to continue the development of new technologies that may provide superior and sustainable outcomes. This study aimed to report the mid-term safety and efficacy outcomes of consecutive patients who received a 3D-printed titanium cage and dynamic hindfoot fusion nail combination fixation for limb salvage in the setting of Charcot arthropathy.

A retrospective chart review of patients who underwent hindfoot arthrodesis with a combination of patient-specific 3D-printed titanium cage and dynamic intramedullary nail by a single surgeon was performed. Additional inclusion criteria were a minimum of one-year follow-up and a minimum age of 18 years at the time of surgery. There were no exclusion criteria. This study was conducted at a single academic center and received an exemption from the IRB. Cages were provided under the FDA 520(b) Custom Device Exemption by a single manufacturer, restor3d (Durham, NC). Beyond patient-specific dimensions and anatomic profile, cage design was consistent across cases consisting of titanium 3D-printed in a triply periodic minimal surface structure with a central canal to accommodate an intramedullary nail. A characteristic example is pictured in Fig. 1.

The primary outcome was to establish the safety of the 3D-printed cage. Medical records were reviewed for adverse events including subsequent surgical intervention, and implant survivorship. The secondary outcome was to evaluate the efficacy of the 3D-printed cage. Pain was measured with the 11-point Numeric Rating Scale. Patients also reported pre- and post-operative ambulation status and satisfaction. Radiographs were reviewed to assess post-operative deformity correction and the maintenance of correction at last follow-up. Demographic data were also collected, including age, smoking status, work status, and medical history.

Thirteen sequential surgical cases were identified, and all met the inclusion criteria. Surgeries occurred between October 2018 and October 2020. Patients had a mean age of 63 years (range 39–80 years). All were non-smokers at the time of surgery. The most common relevant medical condition and indication was Charcot arthropathy, which was present in 10 of 13 patients. Seven of 13 patients were diagnosed with diabetes mellitus. Other common indications included arthritis (6 of 13 cases) and failed prior surgery (4 of 13 cases). Demographics and indications are summarized in Table 1. Mean follow-up was 3.72 years (range 2.67–4.60 years).

Table 1: Demographics and Indications for Surgery

Case (#)	Age at Time of Surgery (Years)	Comorbidities	Neuropathy/Charcot Arthropathy (Yes/No)	History of Prior Surgery (Yes/No)	End-Stage Arthritis (Yes/No)	Instability (Yes/No)	Cyst Formation (Yes/No)	Avascular Necrosis (Yes)	Subchondral Collapse (Yes/No)	Pre-operative Ambulation Status	Post-operative Ambulation Status
1	80	A-fib, CHF, Gout, HLD, Hx of DVT, Lymphoma	Yes	Yes	No	Yes	No	No	No	Assistive Device	Assistive Device
2	68	RA	Yes	Yes	No	No	No	No	No	Independent	Independent
3	73	CAD, DM, HLD, HTN, Lupus, Sjogren	Yes	No	Yes	No	Yes	No	No	Assistive Device	Independent
4	47	DM, HLD, HTN, Obesity	Yes	No	Yes	No	No	No	No	Assistive Device	Independent
5	64	A-Fib, DM, Hx of PE, Hx of PJI, Fibromyalgia, RA	Yes	No	No	No	No	No	No	Assistive Device	Assistive Device
6	70	Gout, HTN, OSA	No	No	Yes	No	No	Yes	Yes	Assistive Device	Independent
7	48	DM, HTN, Obesity	Yes	No	No	No	No	No	No	Assistive Device	Independent
8	60	Hypothyroidism	No	No	Yes	No	No	No	No	Assistive Device	Independent
9	67	DM, HLD, HTN	Yes	No	No	No	No	No	No	Independent	Independent
10	39	CMT, HLD, HTN	Yes	Yes	No	Yes	No	No	No	Independent	Independent
11	67	DM, ESRD, HTN	Yes	Yes	No	No	No	No	No	Independent	Independent
12	63	A-fib, DM, HLD, HTN	Yes	No	Yes	No	No	No	No	Independent	Independent
13	71	ESRD, FVL, HTN, Hx of TIA, Liver cysts, Lung nodules, Prostate cancer	No	No	Yes	No	No	No	No	Independent	Independent

Abbreviations: A-fib, atrial fibrillation; CAD, coronary artery disease; CHF, congestive heart failure; CMT, Charcot-Marie-Tooth; DM, diabetes mellitus; DVT, deep venous thrombosis; ESRD, end-stage renal disease; FVL, Factor V Leiden; HLD, hyperlipidemia; HTN, hypertension; Hx, history; OSA, obstructive sleep apnea; PE, pulmonary embolism; PJI, periprosthetic joint infection; RA, rheumatoid arthritis, TIA, transient ischemic attack

Regarding the primary outcome, four patients experienced an adverse event, all requiring a subsequent surgical intervention. The average time to subsequent surgical intervention was 1.95 years after the index procedure. In two cases, the dynamic intramedullary nail was removed due to loosening or interlock screw failure, but the cage remained intact and implanted. In the other two cases, the patients healed their surgical wound from the index procedure but went on to develop an unrelated infection that ultimately indicated below-knee amputation (BKA). None (0 of 4 events) of the adverse events were related to the 3D-printed cage. As of the most recent follow-up, 11 of 13 cages remain implanted, with two cages having been explanted in the setting of the aforementioned BKAs. Adverse events are summarized in Table 2. Implant survivorship is presented in Fig. 2.

Table 2

Summary of Safety Events
Case (#)	Days to Reoperation	Description	Outcome	Device Related? (Yes/No)
2	1347	Patient demonstrated good interval healing of the surgical wound before subsequently developing a superficial wound infection in an unrelated traumatic injury. The patient underwent wound debridement during which a distal interlock screw was found to have failed allowing distal migration of the intramedullary nail. The original nail was removed and replaced with a static nail. The 3D-printed cage remained implanted.	Revision to static intramedullary nail	No
4	582	Patient demonstrated good interval healing of the surgical wound before subsequent presentation with sepsis due to an unrelated infection, which progressed to and redness, warmth, and swelling of the lower extremity that had undergone the index procedure. Patient ultimately underwent below-knee amputation.	Amputation	No
5	680	Patient demonstrated good interval healing of the surgical wound before subsequent presentation with pain on ambulation and was found to have loosening of the intramedullary nail. The intramedullary nail was removed. The ankle cage was found to be intact and to have successfully fused and therefore remained implanted.	Removal of hardware (intramedullary nail)	No
9	231	Patient demonstrated good interval healing of the surgical wound before subsequent presentation status post a ground-level fall and traumatic laceration of the ankle, which had become infected. Patient underwent below-knee amputation.	Amputation	No

Regarding the secondary outcome, survey data were collected from all patients. Patients reported a mean pre-operative pain score of 6.6 ± 2.9 points. At the last follow-up, the mean pain score was 2.0 ± 1.7 points. Pain scores are summarized in Table 3. Six of 13 patients reported the ability to ambulate independently without an assistive device pre-operatively. Post-operatively, 11 of 13 patients were able to ambulate independently. At the last follow-up, patients were also queried for willingness to undergo the same treatment after experiencing the procedure and recovery. Patients who required subsequent surgical intervention were queried regarding preference after the subsequent intervention. All patients responded they would pursue the same treatment and would not have preferred BKA as the index procedure.

Table 3

Pain Scores
Case (#)	Pre-Operative Pain (11-points NRS)	Post-Operative Pain (11-point NRS)
1	8	3
2	9	2
3	9	1
4	6	3
5	3	1
6	5	2
7	9	6
8	7	2
9	9	4
10	5	2
11	0	0
12	6	0
13	10	0
Mean	6.6	2.0

Regarding deformity correction, mean initial coronal correction was 25 degrees, and the mean initial sagittal correction was 6 degrees. At last follow-up, the mean loss of coronal correction was 0.5 degrees, and the mean loss of sagittal correction was 2 degrees. All patients demonstrated adequate fusion. Correction is tabulated by patient in Table 4.

Table 4

Initial Deformity Correction and Correction Maintenance
Case	Initial Correction (degrees)		Maintenance (loss of degrees)
Case	AP	Lateral	AP	Lateral
1	22	13	1	1
2	25	10	0	6
3	6	3	1	1
4	18	12	N/A	N/A
5	25	8	0	5
6	13	0	2	0
7	57	7	0	5
8	12	5	1	1
9	29	5	N/A	N/A
10	19	7	0	0
11	38	2	0	2
12	47	9	1	3
13	15	0	0	1
Mean	25.1	6.2	0.5	2.3

This case series reports mid-term outcomes of patients who underwent hindfoot arthrodesis with a patient-specific, 3D-printed titanium cage and dynamic intramedullary nail as a limb-sparing surgery. A majority of patients in this study had a history of diabetes complicated by neuropathy and Charcot arthropathy (10 of 13 patients). The other primary indication was severe arthritis (3 of 13 patients). Overall, pre-operatively, patients in this study suffered foot and ankle degeneration, resulting in high pain scores, compromised ability to ambulate independently, and comorbidities suggestive of poor wound healing potential and higher risk for infection. Recent studies have reported promising outcomes from the use of 3D-printed cages in ankle fusion. Though previously reported populations are small, potential benefits include fusion rates ranging from 75–93%, correction within a single surgery, reduced infection rates ranging from 0–15%, and deformity correction that is durable through mid-term follow-up, all of which contribute to improved functional outcomes.^7,11–14 The results of this study were also promising with 13 patients achieving fusion and 11 of 13 patients benefiting from successful limb salvage. There were also substantial improvements in pain scores and ambulatory status and high patient satisfaction.

Reported outcomes of TTC fusion typically range from 86–100%.^5,15 However, fusion rates drop precipitously in the setting of Charcot arthropathy, non-traumatic osteoarthritis, or large bone defects with reported fusion rates commonly under 60% and infection rates commonly over 30%.^5,15,16 Bulk femoral allograft is often used to augment TTC fusion in the setting of critical-sized defects but also suffers from low fusion rates, increased risk of infection, and graft collapse that compromises the correction.^11,17 In a systematic review of 175 cases of TTC arthrodesis with structural allograft in a general population, Cifaldi et al. reported a union rate of 67% and a complication rate of 27%, of which the most common were infection, allograft fracture or failure, stress fracture, and painful hardware.¹⁷ This study reports a similar complication rate (4 of 13 patients). However, no complications were directly associated with the 3D-printed titanium cage and all patients demonstrated good surgical wound healing and fusion following the index procedure. Additionally, in regard to the two cases of infection that indicated re-operation for BKA, the infections were attributed to trauma that occurred after complete healing of the surgical site and are not related to the study device or procedure. Overall, achieving union in 13 of 13 patients and limb salvage for 11 of 13 patients is remarkable in this population and is within the 71–93% limb salvage rate reported by studies of TTC arthrodesis with structural allograft in a healthier general population.^5,17

This study demonstrates the benefits of a non-biologic, 3D-printed implant and underscores the challenges of treating a medically complex, neuropathic population prone to trauma and infection. This promising safety profile, with only two of 13 3D-printed cages being explanted in the setting of BKA, corroborates previous reports of 3D-printed foot and ankle cages such as those by Abar et al. and Steele et al.^7,11 Besides the utility of 3D-printed cages in limb salvage, the 3D-printed cages used in this study as provided a powerful means of durable deformity correction, though future studies are necessary to assess this effect in particular. Finally, patients were also highly satisfied with this procedure, benefiting from substantial reductions in pain and improved ability to ambulate independently. This satisfaction is further supported by the fact that all patients, including the two patients who progressed to BKA, stated they would attempt the procedure again.

This study is limited due to its design, lack of comparison group, and small sample size. Due to the small number of patients reviewed, only descriptive statistics were calculated. This in combination with the lack of a comparison group prevents the determination of causal relationships.

This study reports mid-term outcomes of TTC arthrodesis with a patient-specific 3D-printed titanium cage and dynamic intramedullary nail for limb salvage in patients with Charcot arthropathy or non-traumatic arthritis. The results demonstrate no implant-related complications and promising outcomes in terms of patient reported pain, postoperative ambulation, radiographic fusion, deformity correction, and patient satisfaction. The data build on previous reports of good safety and efficacy of 3D-printed cages in ankle fusion and similarly demonstrate good safety and efficacy in a more challenging patient population where delayed healing and higher infection rates often result in limb loss. While these data are promising, further studies are required to demonstrate long-term outcomes.

Hofbauer LC, Busse B, Eastell R et al (2022) Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diabetes Endocrinol Mar 10(3):207–220. 10.1016/s2213-8587(21)00347-8
Jeffcoate WJ, Game F, Cavanagh PR (2005) The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet Dec 10 366(9502):2058–2061. 10.1016/s0140-6736(05)67029-8
Rogero R, Tsai J, Fuchs D, Shakked R, Raikin SM (2020) Midterm Results of Radiographic and Functional Outcomes After Tibiotalocalcaneal Arthrodesis With Bulk Femoral Head Allograft. Foot Ankle Spec Aug 13(4):315–323. 10.1177/1938640019863260
DeVries JG, Berlet GC, Hyer CF (2013) Predictive risk assessment for major amputation after tibiotalocalcaneal arthrodesis. Foot Ankle Int Jun 34(6):846–850. 10.1177/1071100712472488
Jeng CL, Campbell JT, Tang EY, Cerrato RA, Myerson MS (2013) Tibiotalocalcaneal arthrodesis with bulk femoral head allograft for salvage of large defects in the ankle. Foot Ankle Int Sep 34(9):1256–1266. 10.1177/1071100713488765
Bussewitz B, DeVries JG, Dujela M, McAlister JE, Hyer CF, Berlet GC (2014) Retrograde Intramedullary Nail With Femoral Head Allograft for Large Deficit Tibiotalocalcaneal Arthrodesis. Foot Ankle Int 2014/07/01(7):706–711. 10.1177/1071100714531231
Abar B, Kwon N, Allen NB et al (2022) Outcomes of Surgical Reconstruction Using Custom 3D-Printed Porous Titanium Implants for Critical-Sized Bone Defects of the Foot and Ankle. Foot Ankle Int Jun 43(6):750–761. 10.1177/10711007221077113
Kowalski C, Stauch C, Callahan R et al (2020) Prognostic risk factors for complications associated with tibiotalocalcaneal arthrodesis with a nail. Foot Ankle Surg Aug 26(6):708–711. 10.1016/j.fas.2019.08.015
Kelly CN, Miller AT, Hollister SJ, Guldberg RE, Gall K (2018) Design and Structure-Function Characterization of 3D Printed Synthetic Porous Biomaterials for Tissue Engineering. Adv Healthc Mater Apr 7(7):e1701095. 10.1002/adhm.201701095
Kelly CN, Lin AS, Leguineche KE et al (2021) Functional repair of critically sized femoral defects treated with bioinspired titanium gyroid-sheet scaffolds. J Mech Behav Biomed Mater Apr 116:104380. 10.1016/j.jmbbm.2021.104380
Steele JR, Kadakia RJ, Cunningham DJ, Dekker TJ, Kildow BJ, Adams SB (2020) Comparison of 3D Printed Spherical Implants versus Femoral Head Allografts for Tibiotalocalcaneal Arthrodesis. J Foot Ankle Surg Nov-Dec 59(6):1167–1170. 10.1053/j.jfas.2019.10.015
Dekker TJ, Steele JR, Federer AE, Hamid KS, Adams SB (2018) Jr. Use of Patient-Specific 3D-Printed Titanium Implants for Complex Foot and Ankle Limb Salvage, Deformity Correction, and Arthrodesis Procedures. Foot Ankle Int Aug 39(8):916–921. 10.1177/1071100718770133
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The authors declare no competing interests.

Outcomes of Charcot Arthropathy Limb Salvage with Patient-Specific 3D-Printed Cage and Dynamic Hindfoot Fusion Nail Combination Fixation

Status:

Version 1

Abstract

Figures

INTRODUCTION

METHODS

RESULTS

DISCUSSION

CONCLUSION

References

Additional Declarations

Status:

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