complications of ankle fractures in diabetic patients

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COMPLICATIONS OF ANKLE FRACTURES IN DIABETIC PATIENTS

Christopher Bibbo, DO, Sheldon S. Lin, MD, Heather A. Beam, BS, and Fred F. Behrens, MD

Ankle fractures in patients with diabetes mellitus (DM) have long been recognized as a challenge to practicing clinicians in terms of delays in fracture healing, difficulties with wound healing, and the development of Charcot arthropathy. Significant controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation (OlUF). Despite these well-known management difficulties of ankle fractures in diabetic patients, clinical series regarding the treatment of ankle fractures in patients with DM are few. The ex- isting series are reviewed in this article, followed by a discussion of the basic science behind delayed fracture healing and impaired wound healing in diabetics as well as Charcot arthropathy.

CLINICAL SERIES

Kri~tiansen~~ reviewed the results of 10 diabetic ankle fractures treated by operative fixation. Of these patients, 40% were neuropathic. Ninety percent went on to fracture union, 10% developed a Charcot ankle, and 60% developed a surgical infection. Similarly, in a series of 10 diabetic patients with ankle fractures (mean age, 67.5 y) managed operatively, Low and Tanm reported a 40% infection

rate, resulting in two amputations (20%), and the development of one Charcot ankle (in a patient with preexisting neuropathy). These patients were reported not to have peripheral vascular disease. These two early studies alerted clinicians to the poor outcome of diabetic patients with ankle fractures. Significant deficiencies exist in these studies, however. The level of diabetic control and presence of medical comorbidities were not analyzed. Guidelines for operative versus nonoperative management were not discussed.

McCormack and Leitha reported on 26 diabetic ankle fractures, 19 of which (73%) were treated operatively. The mean age was 61 years (range, 43-78 y). In the surgical group, they reported one wound complication (approximately 5%), four infections (approximately 21%) leading to two amputations (approximately 11%), and two deaths (approximately 11740). An overall complication rate of 47% was seen in the operatively treated group versus a 0% complication rate in patients treated noninvasively. These investigators suggested, in light of the high surgical complication rate for elderly, low-demand patients, that surgical intervention may be ill advised and that a malunion may be an acceptable outcome. Several factors, such as the degree of diabetic control and the presence of neuropathy or peripheral vascular

From the Orthopaedic Research Laboratory (HAB), Foot and Ankle Division (SSL), Department of Orthopaedics (CB, FFB), New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey

ORTHOPEDIC CLINICS OF NORTH AMERICA

VOLUME 32 * NUMBER 1 * JANUARY 2001 113

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disease, were not reported, and the existence of any prodromal comorbidities was not reported.

In data presented at the 1994 annual Ortho- pedic Trauma Association meeting, Zinar and Brown97 reported on 14 diabetic ankle fractures, (patient age range, 36-88 y). The presence of neuropathy, peripheral vascular disease, or other markers of advanced disease was not reported. The overall complication rate for treating diabetic ankle fractures was 43%. The incidence of types 1 and 2 DM was approximately equal. Patients with type 1 DM showed a 63% complication rate versus a 17% complication rate for type 2 DM. Of the 10 patients who underwent operative fixation, one would dehiscence (lo%), two infections (20%), and one loss of fixation (10%) occurred, yielding an overall 40% surgical complication rate. The complication rate for closed treatment of diabetic ankle fractures was 50%, which included two infected ulcers. Markers for increased risk for treatment complications included talar subluxation, insulin-dependent diabetes mellitus (IDDM), and more severe grade ankle fractures. The investigators concluded that because of the high complication rate (50%) in patients requiring nonoperative management (closed reduction and a molded cast), surgical intervention may be the pre- ferred treatment. In support of these data, Connolly and Csencsitzl'j reported five diabetic ankle fractures (all IDDM patients; mean age, 40 y) treated with casting. Two patients developed an infection, resulting in one amputation and two developed a Charcot joint. Two patients required ankle fusion after infection or a Charcot arthropathy. One patient developed a malunion (terminal treatment), and another underwent delayed operative fixation with a resultant functional fibrous ankylosis. These investigators concluded that early operative intervention is preferable for patients with DM and ankle fractures. Holmes and Hill43 reported similar results in their study of DM foot and ankle fractures. Of 18 patients, 6 had ankle fractures (all type 2 diabetics; age range, 42-78 y). Five of 6 operatively treated patients healed, with 1 deep infection that healed subsequently. A Charcot ankle developed in one of three patients who were treated by nonoperative method. These series seem to indicate that Charcot changes and infectious complications occurred more frequently in patients who had fractures treated by casting.

Schon et a P reviewed 28 neuropathic dia-

betic ankle fractures, which included 15 nondisplaced ankle fractures and 13 displaced ankle fractures. Treatment for nondisplaced diabetic ankle fractures consisted of conserva- tive management by delayed immobilization (n = 3), immediate immobilization with non- weight bearing for 3 months (n = 5), or immobilization and initial non-weight bearing for 9 months (n = 7). All of these nondisplaced ankle fractures healed, with no patients developing a Charcot joint or infection. The 13 displaced ankle fractures were treated by casting (n = 4) or operative intervention (n = 9). Closed treatment of the displaced ankle fractures resulted in a 100% nonunion/ malunion rate, with 3 (75%) fracture ulti- mately requiring ankle fusion. The fourth fracture was treated by late ORIF at three months. Operative fixation of displaced ankle fractures resulted in one infected nonunion (8.3%), one wound complication requiring a free flap (8.39'0)~ one Charcot ankle requiring fusion (8.39'0)~ and one failure of fixation (8.3%). No infections or amputations were reported. The poor clinical outcome of nonoperative intervention in displaced ankle fractures in patients with DM portends the need for surgical intervention. One weakness of this clinical series is the lack of a randomized prospective trial.

Costigan and Thordars~n'~ presented their experience in surgically managed diabetic ankle fractures at the annual Orthopaedic Trauma Association meeting in 1997. They treated 52 diabetic ankle fractures operatively, of which 60% were IDDM patients, and 15% were neuropathic. Of the neuropathic patients, 75% (6 of 8) experienced a surgical complication, whereas 63% of patients show- ing preoperative evidence of peripheral vascular disease incurred a surgical complication. Diagnoses of neuropathy and peripheral vascular disease were found to be statistically significant factors for the development of a complication in diabetic patients. In this series, a surgical infection rate of 13.5% was present, with infection resulting in one amputation (2%). No deaths occurred in the operatively treated ankle fracture patients with IDDM. Charcot ankle changes developed in 6% of patients. A trend toward complications (but not statistically significant) was noted in patients with retinopathy, nephropathy, and hypertension. The type of ankle fracture or dependence on insulin did not correlate with outcome.

Blotter et a18 reported a comparative cohort

COMPLICATIONS OF ANKLE FRACTURES IN DIABETIC PATIENTS 115

analysis of 21 operatively treated DM ankle fractures (including three open fractures) versus 23 matched controls of non-DM, surgically treated ankle fractures. A statistically higher complication rate was noted in the DM group (45%) versus the non-DM, surgically treated ankle fractures (15%). The age range was 19 to 77 years (median age, 55 y), with one third of patients having IDDM and two thirds having non-insulin dependent diabetes mellitus (NIDDM). The IDDM patients incurred a 57% complication rate versus a 36% complication rate for the NIDDM patients. Seven infections (21%), two amputations (9.5%), the development of two Charcot joints (9.5%), and one nonunion (4.7%) were re- corded. Two of the three open fractures (67%) developed an infection. Of the patients, 62% sustained a comorbid medical condition in association with DM. Four patients (21%) were neuropathic, whereas only one patient had peripheral vascular disease (who incurred an infection). Of the patients without a medical comorbidity, 6770 developed a surgical complication. Of patients not experienc- ing a post-operative complication, 67% did have a preexisting comorbid medical state in association with DM. These investigators concluded that patients with DM are at increased risk for complications (2.76-fold greater risk) and that strict adherence to a postoperative protocol is crucial to the outcome of surgical management of diabetic ankle fractures.

Conclusions from these studies are as fol- lows. First, diabetic ankle fractures heal, but significant delays in bone healing exist. Sec- ond, patients with DM are at risk for wound and soft tissue problems associated with ankle fractures. Third, Charcot ankle arthropathy occurs more commonly in patients who were undiagnosed and immobilized late43 or have a displaced ankle treated nonopera- ti~ely.7~ Understanding the basic science behind the pathogenesis of these complications may provide insight on how best to manage patients with DM and ankle fractures to avoid these complications.

Delayed Fracture Healing

Delays in healing of nonoperatively and operatively treated fractures in type 1 and 2 diabetic patients are well documented, unit- ing at 187% (in type 1 DM) and 186% (in type 2 DM) of the time required for fractures to

heal in patients without DM.59 Clinically, Si- nacores3 showed that diabetic ankle fractures heal within 83 + 22 days of fracture (Fig. 1).

Laboratory studies using several animal models support the concept of delayed fracture healing in DM. Herbsman et al4l* 42 first showed that the tensile strength of fracture callus in diabetic rats is considerably less than in normal animals. Harris et a13* followed with an experimental model of uncontrolled DM that showed a reduced vascular response during the fracture healing process lasting 4 to 8 weeks, corresponding to mechanical tensile strength." Experimentally, bone healing seems to stagnate in untreated diabetic animals.= Dixit and EkstromZ investigated the healing of artificially created femoral bone defects in alloxan-treated diabetic rats. At twenty-one days after surgery, the bone defect was filled 79% with new bone in control animals, whereas only 38% of new bone occu- pied the defect in untreated diabetic animals. By contrast, the defect in insulin-treated diabetic animals was filled with significantly greater amounts of new bone formation (59%). Similarly a greater amount of calcium was deposited in the control and insulin- treated diabetic animals compared with the untreated diabetic animals at fourteen and twenty one days after surgery. Funk et al3I reconfirmed that the recovery of structural and material strength of femur €ractures in DM rats is delayed significantly compared with control values. At two time points (3 and 4 wk), fractured femora in rats with DM exhibit inferior healing compared with that of intact contralateral femora in terms of torque failure, failure to stress, structural stiffness, and material stiffness.

Impaired collagen synthesis is theorized to be one cause of delayed fracture healing. In- vestigations have shown that type X collagen synthesis is decreased in DM fracture callus, contributing to delays in fracture healing in diabetic patients.89 This decreased collagen production in animals with DM occurs in bone and cartilage and correlates with the degree of hyperglycemia.s6 In experimental diabetic rat models, type 1 collagen and os- teonectin were shown to be decreased mark- edly in early hard callus, in addition to the number of chondrocytes expressing type 2 collagen in soft callus.n

Other studies show that DM bone metabolism is impaired by the inability to maximize bone turnover and 82, 94 This situation in part may be caused by decreased

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Figure 1. A, Radiograph of a closed supination external rotation type 2 right ankle fracture in a 54-year-old man with type 2 diabetes mellitus and neuropathy. B, Despite therapy with short leg cast and nonweightbearing for 3 months, with conversion to short leg walker use for an additional 3 months, the fracture still had not healed.

gut calcium absorption in diabetics.76 By vir- tue of decreased circulating levels of 1,125- dihydroxyvitamin Dan and decreased gut calcium binding bone mineral density also is decreased in diabetics."

Currently, control of blood glucose seems to be an important factor in the overall regulation of fracture healing!, In experimental ectopic bone plaques, reduction in cellular proliferation, delays in chondrogenesis, and vascular invasion for enchondral ossification were nearly reversed by the administration of insulin.91 Similar results of improved cellular proliferation were noted by the authors' laboratory studies under conditions of improved glucose control.6

There currently is little clinical literature regarding the application of a growth factor as a fracture healing adjunct in a patient with DM who sustains a fracture. Several animal studies support this concept and show improved bone healing in DM animals using basic fibroblast growth factor.27, Fibrin stabilizing factor (Factor XIII) is another factor under investigation for clinical use. In DM rats, the addition of Factor XI11 showed a

positive effect on wound healing with increased bone depo~i t ion .~~

Wound Healing

Wound healing in DM has long been recognized as a major complication of the disease and a formidable challenge to overcome. Complications relating to wound healing are a major source of morbidity and potential mortality in surgical patients with DM (Fig. 2). A complex integration of events occurs in normal wound healing, influenced by many cytokines. To understand the pathogenesis of altered wound healing in diabetics, the two fundamental pathophysiologic states, hyperglycemia and hypoxia, must be explored.

Hyperglycemia is the essence of DM. Alter- ations in insulin levels or insulin receptor affinity result in excess blood glucose, recognized most easily on blood glucose analysis. Structural and functional proteins (e.g., enzymes) exposed to prolonged periods of elevated blood glucose engage in enzymatic glycosylation (Schiff base and Amadori prod-


Figure 2. A, Postsurgical view of the ankle of a 62-year-old man with type 1 diabetes mellitus with neuropathy who sustained a bimalleolar ankle fracture. Wound-healing problems with dehiscence and soft-tissue sloughs are present. B, After surgical irrigation and debridement, exposed metal was found along the fibula, after which the patient was initiated on KCI VAC (Vacuum-Assisted Closure) therapy. C, After 2 weeks on KCI therapy, a granulating tissue bed was found in the wound, after which the patient underwent re-epithelialization without sequelae.

ucts). Over time, these proteins may undergo nonenzymatic glycosylation reactions yielding irreversible advanced glycosylation products. These advanced glycosylation products attach to collagen, basement membrane, low- density lipoproteins, and inflammatory cell receptors. Over time, these products accumu- late in tissues.2o Measurement of glycosylated hemoglobin levels (hemoglobin At) allows

for an average estimate of blood glucose levels over the 120-day life span of the red blood cell and is a useful clinical marker for degree of blood glucose control over this period. Some tissues, such as the kidney, nerves, blood vessels, and eye lens, do not require insulin for glucose transport; hyperglycemia results in elevated intracellular glucose, which is shunted to the sorbitol pathway. The

118 BIBBO et a1

end result is decreased myo-inositol levels and cell damage, as evidenced by the neuropathy of DM.20 These events are believed to be responsible for nerve and vessel damage in DM.

Tissue hypoxia is a common secondary phenomenon of DM. DM affects small and large vessels. Diabetics show regional and localized ischemia, with large vessel arterioscle- rosis, particularly of the lower extremities, and localized small vessel angiopathy." Com- pounding this ischemia, it has been shown that patients with DM have a higher blood viscosity; their red blood cells are less de- formable; and glycosylated hemoglobin has a higher affinity for oxygen, impairing oxygen delivery to ischemic tiss~es.3~

The combination of local ischemia and elevated blood glucose creates a poor environment for wound healing. Under hypoxic conditions, fibroblast migration is and fibroblasts lose the ability to replicate. Wound collagen deposition is directly proportional to wound oxygen tension and perfusi0n,4~ and collagen production is limited severely in DM

The poorly healing, ischemic DM wound results in an environment that has an increased susceptibility to infection.75 It is evident that any local infection compromises the wound healing process further. This compro- mise in wound healing in part is believed to be caused by the release of bacterial enzymes and metalloproteinases, which degrade fibrin and growth factors.87 Simple experiments have shown that the presence of greater than lo5 bacteria per 1 g tissue in healthy wounds imparts a less than 19% chance of successful wound closure.56 Iatrogenic factors, such as rough tissue handling and selection of certain suture materials, may affect the healing of surgical wounds of patients with DM. For example, the presence of a foreign body, such as braided silk sutures, decreases the number of bacteria to cause infection by a factor of 10, OO0.26 In a state of compromised wound healing, the choice of wound dressing may have deleterious effects. Commonly used wound dressing agents, such as povidone- iodine, have shown no beneficial effect on epithelialization. Povidine-iodine has been shown to delay wound healing in DM models and in steroid-depressed ~ o u n d s . 6 ~

Gross or macroscopic measurements to predict wound healing in diabetics generally are markers of large vessel patency and local small vessel perfusion of the skin. Palpable

87

pulses in a patient with DM traditionally have been thought of as a sign of good distal flow. The use of semiquantifiable values, such as the ankle-brachial index, may not be reli- able in patients with DM because of medial calcific sclerosis (Monckeberg's) and inability to achieve vessel compression adequately. One valuable clinical marker of adequate local perfusion for healing in patients with DM is transcutaneous oxygen tension (TcPO,) measurements. Measurement of tissue perfusion by TcPOz allows for assessment of large vessel inflow and local small vessel angiopathy. TcP02 measurements are valuable in predicting healing in patients with DM, despite having ankle pressures equal to those of non-DM subjects?O A TcPO, value of 30 mm Hg has been shown consistently to be the minimum value required not only for healing of diabetic surgical wounds, but also the successful outcome of lower extremity diabetic infections. Values less than 30 mm Hg may indicate the need for angiography.5, 13, 21, 48 It also has been suggested that a TcP02 increase of 10 mm Hg or more after oxygen inhalation may be a better predictor of potential healing than static TcPO, measurements in diabetic limbs.9

Additional risk factors for poor healing in patients with DM (besides elevated glycosylated hemoglobin) include vasculopathy, smoking, hypertension, dyslipidemia, and advanced age.62 Increased body mass index and delays in starting treatment of greater than 2 weeks have a negative effect on healing time.83

Basic science advances have increased understanding of wound healing, providing insight into treatments to optimize healing potential in patients with DM. Vital to the wound healing process is the initial inflammatory reaction. The weak initial inflammatory response in human DM wounds results in not only delayed restoration of the epidermal barrier5, but also decreased tensile strength of healing DM wounds.87 Central to the inflammatory phase is the phagocytic cell: granulocytes and macrophages. Granu- locyte function is impaired in poorly controlled patients with DM, slowing the healing inflammatory response and making the wounds more susceptible to infection?, 70, 87

Impaired phagocytosis by granulocytes, decreased granulocyte chemotaxis, and inter- ference with collagen synthesis are obstacles that must be overcome for DM wounds to heal.4, 70, 75


Control of blood glucose traditionally has been considered an important factor for maintaining a proper environment for wound healing.32 Although the degree of acute blood glucose control and long-term blood glucose control (as shown by hemoglobin A&) has not been addressed specifically in most clinical series on ankle fractures in patients with DM, it is evident that the impaired granulocyte phagocytosis seen in patients with DM is par- tially responsible for the suboptimal inflammatory response of wound healing and infection surveillance. This environment is impaired further by hyperglycemia and improved by control of blood glucose.7o Acute and long-term control of blood glucose are considered important in healing of surgical wounds in diabetics.

The adverse effects on wound healing resulting from uncontrolled blood glucose alter- ing the inflammatory response have been corroborated in the laboratory. A lowered number of leukocytes and decreased levels of interleukin-6 have been shown in experimental diabetic animal wounds, correlating with an altered late inflammatory response and delayed wound healingz8 Diabetic animal models have shown gross decreases in inflammatory cell infiltration and vascularity; increased wound edema, vascular degeneration, and necrosis92; and decreases in the quantity of reparative collagen, qualitative decreases in reparative collagen cross-linking, and impaired capillary morphogenesis.2* Heat-shock proteins, responsible for stabilization of stressed intracellular processes, are delayed in their expression by 3 days in diabetic animal models. This delay corresponds to a lag in wound healing, attributed to the impaired inflammatory response in animals with DM.65

This literature review shows the various factors associated with the impaired wound healing process of patients with DM. Clini- cians may optimize the wound healing environment by ensuring appropriate insulin therapy, maintaining tissue oxygenation, and optimizing the limb vascularity when treating a patient with DM who sustains an ankle fracture. Although specific recommendations regarding these potential wound healing adjuncts await completion of clinical trials, the future seems promising.

CHARCOT ARTHROPATHY

More than 16 million people in the United States have DM. Of these patients, 6.0% to

41.6% develop peripheral neuropathy within the first decade of DM onset.lO, 17, 57, In contrast, only 0.1% to 2.5% of all DM patients are diagnosed with Charcot arthropathy.= A review of the literature shows that 5% to 10% of all DM patients who sustain an ankle fracture develop Charcot arthropathy. Increased understanding into the proposed mechanisms of Charcot arthropathy may provide further insight into the role of trauma and the development of Charcot arthropathy.

Charcot arthropathy was first illustrated in 1868 by the French neurologist C h a r c ~ t . ' ~ Many issues, such as its cause, proposed pa- thomechanism, and predictive risk factors, for the development of Charcot arthopathy still are unknown. A warm, swollen, erythema- tous limb often signifies the early clinical presentation of Charcot arthropathy. Many patients do not remember the inciting event and remain undiagnosed until late into the destructive process. Radiographic findings of Charcot arthopathy range from microfrac- tures, to progressive bone fragmentation, to severe joint destruction and subluxation as a result of repetitive ligamentous and bone injuries. Despite the recognition of Charcot arthropathy since the late MOOS, the specific pathogenesis underlying the joint destruction process is undetermined.

Current research has concentrated on two major theories: (1) repetitive minor trauma in the presence of neuropathy and (2) vascular changes secondary to autonomic dysfunction. Although it is accepted that both of these cofactors play a role in the development of Charcot arthropathy, it is unclear which mechanism imparts the greatest influence.

The development of neuropathy seems to be crucial in the development of Charcot arthropathy. The small nerve fibers initially are affected in the process of developing DM peripheral neuropathy. A reduction in pain and thermal sensation occurs, gradually prog- ressing to affect light touch and propriocep- tion capabilities.23 Secondary to the reduction of peripheral sensorineural function, patients become increasingly susceptible to unrecog- nized traumatic events (i.e., ankle sprain). If undetected, this minor trauma may initiate a cycle of repetitive injury and destructive joint arthr~pathy.~~. 46 Slowman-Kovacs et alE theorized that peripheral neuropathy reduced the normal muscle reflexes that protect the innervated extremity. The specific weakness of affected muscle (associated with antagonist group) allows for progressive deformities that

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lead to eccentric loading on the affected joint. Pathologic alignment allows for progressive, undetected, repetitive trauma and excessive joint range of motion, leading to progressive tissue damage.

Several studies have attempted to analyze the impact of sensory denervation on articular surface and its relationship to Charcot arthropathy. O’Conner et a17’ theorized that joint instability seems to be the crucial factor of articular degeneration in patients predis- posed by sensory neuropathy. In a dog model for Charcot arthropathy (dorsal root gangli- onectomy [DRG] fourth lumbers to first sacral vertebrae), OConner et al7I analyzed the effect of sensory denervation and joint stability on the anterior cruciate ligament (ACL)- deficient knee. The first group of dogs underwent DRG only, whereas the second group was subjected to ACL transection 2 weeks after DRG. One control sensory intact group underwent ACL transection only. The DRG- only group failed to show changes in the biomechanical, metabolic, histologic or macroscopic parameters of articular cartilage 16 weeks after deafferentation. In contrast, the DRG and ACL transection group had significant pathologic joint changes at 3 weeks. These joint lesions were more severe and occurred more rapidly in the DRG and ACL transection group than in dogs with ACL transection alone with intact sensitivity.

Finsterbush and FriedmanZ9 analyzed the effect of unilateral surgically induced sensory denervation on knee joints of immobilized and nonimmobilized rabbits. These authors found significant tissue changes (including loss of normal chondrocyte columnation, thickening of calcified cartilage and subchon- dral bone region, loss of glycosaminoglycan, and areas of complete acellularity) within the deeper cartilage layers of the nonmobilized, denervated animals. In contrast, animals that were denervated but also immobilized showed only mild articular damage occurring within the superficial cartilage layer. These investigators suggested that denervation may alter cartilage nutrition and that immobilization plays a crucial role in moderating the process of articular destruction.

This concept is corroborated by clinical ob- servations that the presence of peripheral neuropathy, with an inciting traumatic event (e.g., an ankle fracture), commonly leads to Charcot arthropathy, especially in a late diagnosed or inappropriately immobilized patient.43 Several case reports document similar

clinical scenarios of minor joint trauma in neuropathic patients, resulting in rapid progression to Charcot arthropathy.34, = Lis franc fracture-dislocation, bone fragmentation, and joint subluxation characterized the radiographic findings.=

Investigators have theorized about vaso- neural mechanisms for the development of Charcot arthropathy. Marked increases in peripheral blood flow have been noted in the limbs of neuropathic DM patients secondary to arteriovenous shunting. Arteriovenous anastomoses are prevalent in the skin and are present in bone and joints. These anastomoses are richly innervated and controlled primarily by the sympathetic nervous system. When sympathetic innervation is abolished because of denervation (i.e., severe neuropathy), the loss of constriction of arteriovenous anastomoses results in maximal dilation? Increases in arteriovenous shunting in neuropathic limbs lead to greater than normal blood flow and elevated venous pressure.’l, 69, 73 This excessive blood flow secondary to peripheral neuropathy may lead to abnormal bone cell activity and eventual reduction in bone density.”, @

Several studies provide scientific evidence supporting this concept. First, Edmonds et alZ4 documented an increased uptake of bone radiopharmaceutical in the feet of neuropathic patients with DM. Gough et a133 investigated osteoclast and osteoblast activity in patients with Charcot neuroarthropathy. Se- rum carboxyterminal telopeptide of type 1 collagen (lCTP), a marker of osteoclastic bone resorption, and serum procollagen carboxyterminal propeptide (PlCP), a marker of osteo- blastic activity (bone formation), were mea- sured. Levels of local lCTP were raised in patients with acute Charcot process, whereas levels of PlCP were normal compared with DM controls. These results suggest an increase in osteoclast activity in acute Charcot patients without an accompanying increase in osteoblast activity, which may be a contributing factor in the pathogenesis of Charcot neu- r0arthropathy.3~ Based on this increased osteoclastic activity, several investigators have suggested a role for osteoclast inhibitors as a medical regimen for Charcot arthropathy.=

Hyperemia and neurovascular changes secondary to an autonomic neuropathy may con- tribute to a generalized osteopenia in patients with DM. In conjunction with a traumatic event, the resultant additional increased blood flow is theorized to increase osteoclast


activity, promote excessive bone resorption, increase fracture risks, and lead to neuropathic Charcot arthropathy.

In 1986, Brodsky,12 reporting on one of the largest series to date, described a classification of neuropathic Charcot arthropathy in the tarsus bones and their natural history of the Charcot process in a statistically significant association according to which anatomic area of the foot and ankle is affected. Type 1 neuroarthropathic foot involves the tarso- metatarsal and navicular cuneiform joint. Type 1 is characterized by symptomatic bone prominence but not persistent instability. Al- though the bone prominence may lead to a soft tissue breakdown, few patients require surgical intervention. Type 2 neuroarthropathic joint involves any or all among the triple or hindfoot joint (i.e., subtalar, talonavi- cular, and calcaneocuboid joint). Type 2 is characterized by persistent instability but is unlikely to produce symptomatic bone prominence and ulceration. Type 3A neuroarthropathic joint involves the tibiotalar joint. These patients have a long period of persistent instability, require long-term immobilization, and produce symptomatic bone prominence more than type 2 but less than type 1. Of all of the groups type 3A is most likely to require surgical reconstruction for the deformity. Type 3B neuroarthropathic foot consists of a neuropathic fracture of the posterior tubercle of the calcaneus.

EichenholtzE is credited with the classic radiographic staging of progressive neuropathic joints from a radiographic viewpoint. Stage 1 is described as the stage of development, with radiographic evidence of debris formation, bone and cartilage fragmentation, and capsular dehiscence with subluxation and dislocation. The clinical presentation consists of acute inflammation with edema, hyperemia, increased warmth, and erythema. Of- ten, this inflammatory stage is mistaken for cellulitis, abscess, and other infection. Stage 2 is the stage of coalescence, with the gradual absorption of fine debris, adherence, coalescence of bone fragments, and characteristic sclerosis of the bone ends. Clinically, there is decreased swelling, warmth, and redness. Stage 3 is the stage of reconstruction, with rounding of bone fragments, sclerosis (secondary to revascularization), and attempts at reformation of the joint architecture. Schon and Marksso have added a stage 0, which represents an at-risk patient-a neuropathic (either diagnosed or undiagnosed) patient

who sustain an acute ankle injury. Neuro- pathic patients with DM who sustain an acute ankle fracture are considered stage 0.

Nonoperative management consists primarily of protection of the neuropathic foot from further trauma. Most authorities agree that repetitive trauma is one of the key factors in the development of Charcot arthropathy.35, 37 If neuroarthropathic changes do occur in the ankle joint, protection from further repetitive trauma by immobilization is the ideal primary treatment for stage 1 neuropathic joint.l*, 8o Protective devices include a caliper (double-upright calf lacer prepared in DM rocker shoe), Charcot restraint orthotic walker, and plastizote-lined clamshell ankle foot orthosis with DM insert.

To date, there are no clear predictive factors for the development of Charcot arthropathy. Sex, age, insulin use, duration of diabetes, retinopathy, proteinuria, level of glycosylated hemoglobin (hemoglobin A&), and history of a previous foot ulceration have had no statis- tical value for prognosticating the development of Charcot a r t h r ~ p a t h y . ~ ~ A delay in treatment or immobilization of neuropathic patients with an ankle fracture seems to pre- dispose patients for Charcot a r th r~pa thy .~~ The current inability to predict who will develop a Charcot joint as a complication of a lower extremity injury has led to the recom- mendation that all diabetic patients who sustain a minor traumatic event seek immediate medical care and proper immobilization. Traumatically induced Charcot ankle arthropathy is a complication that develops not only in the injured joint. Clohisy and Tom~son'~ found that in juvenile DM patients with a foot or ankle fracture, 72% develop a contralateral Charcot arthropathy within 2 months to 5 years after the index fracture. When a fracture is evident, protected weight bearing (for an extended period) should be maintained on the affected side (and the non affected side) in an effort to avoid the development of a Charcot arthropathy (Fig. 3).15, sf 96

Several theories exist regarding the pathophysiology of DM Charcot neuroarthropathy. The presence of neuropathy places a patient even after a minor traumatic event at risk for Charcot joint destruction. Neuropathy is an essential component leading to loss in sensation, abnormalities in joint motion, and altered blood flow. Increases in blood flow and arteriovenous shunting may lead to impaired cellular function, osteopenia, and fracture.

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Figure 3. A, Radiograph of a right trimalleolar ankle fracture in a 60-year-old woman with type 1 diabetes mellitus with neuropathy. The patient presented 12 days after injury. Anteroposterior (s), lateral (C), and mortise (0) radiographic views immediately after surgery show internal fixation in place with restoration of the ankle joint.


Figure 3 (Continued). f-G. Over the next 6 months, progressive collapse of the ankle joint developed, with loosening of medial screw and pin. Charcot arthropathy is evident 6 months after surgery.

Undetected minor traumas to the desensi- tized joint increase the rapidity of neuroarthropathic onset, predisposing the joint to abnormal loading and further destruction. Early detection and consideration of the possible pathomechanisms of Charcot arthropathy provides insight into the management and care for neuropathic patients with DM who sustain ankle fractures.

CLINICAL QUESTIONS

How Should Nondisplaced Ankle Fractures in Patients With Diabetes Mellitus Be Treated?

A nondisplaced ankle fracture, whether as a result of a specific traumatic event or without any recognizable event, typically heals uneventfully with cast immobilization followed by bracing. Schon et a P described a series of 16 neuropathic DM patients with nondisplaced ankle fractures using three treatment protocols: (1) cast or brace for less than 3 months (n = 3), (2) cast or brace for 2 to 3 months with non-weight bearing up to six months (n = 5), and (3) cast or brace for 3 to 9 months with non-weight bearing for the first 1 to 4 months (n = 7). Jn all patients, the fractures healed, and the patient did not progress to Charcot arthropathy. Although

extended non-weight bearing was recommended in the latter two groups, the patients who did not adhere to weight-bearing pre- cautions tended to maintain the fracture reduction and alignment, provided that use of a cast or brace was continued.

The authors’ protocol consists of cast immobilization for a minimum of 8 weeks non- weight bearing. Afterward the patients follow a protocol of brace immobilization in a DM short leg walker or molded, lined, and bivalved AFO for another 8 to 16 weeks with progressive weight bearing, depending on the clinical and radiographic appearance. The authors use a protocol of 25 lb increase at 2 to 4 weeks intervals until 75% of the patient’s weight is achieved. At this time, full weight bearing is allowed.

Patients with nondisplaced ankle fractures typically heal uneventfully and do not progress to Charcot arthropathy (Fig. 4). If displacement does occur, salvage techniques of late ORIF or arthrodesis are recommended to maintain stability and alignment of the ankle joint.

How Should a Displaced Ankle Fracture in a Patient with Diabetes Mellitus Be Treated?

The literature is sparse comparing the clinical outcome of nonoperative versus operative

124 BIBBO et a1

Figure 4. A, Radiograph of a closed supination external rotation type 2 right ankle fracture in a 56-year-old man with type 2 diabetes mellitus. 13, With appropriate therapy of a short leg cast and nonweightbearing for 8 weeks, followed by short leg walker use for an additional 8 weeks, fracture resolution was achieved.

intervention of displaced ankle fractures in patients with DM. Schon et aln described a series of 13 pre-Charcot displaced ankle fractures. Four ankles were treated by closed reduction and casting or bracing (minimum, 3 m). Nine ankles underwent ORIF. The four ankles treated nonoperatively were managed with a cast or brace for a minimum of 3 months, and all progressed to significant Val- gus deformity, non union, or both. Three of 4 ankles required ankle arthrodesis, and one required late ORIF (at three months (Fig. 5). In comparison, nine ankles were treated by

ORIF in the acute setting. The protocol after surgery consisted of immobilization for a minimum of 3 months. Two of the 9 patients were managed with non-weight bearing and casting for 6 weeks (in which one ankle displaced and progressed to an infected nonunion). The other 7 ankles were managed with non-weight bearing and immobilization in a cast or brace for 8 to 12 weeks. These results were superior compared with the other protocol. Only 1 of the 7 ankles showed progressive displacement and required a tibi- ocalcaneal fusion. It is evident from this limited series that displaced fractures treated by closed reduction and casting generally sustain

a progressive malalignment, loss of reduction, and Charcot changes, despite the appropriate non-weight bearing protocol and casting techniques (Fig. 6).

The authors recommend operative intervention of displaced ankle fracture to restore the articular alignment, despite the potential complications of delayed wound healing, infection, and loss of fixation secondary to 0s- teopenia. An improved alignment and rigid fixation minimizes the risks of Charcot arthropathy. Surgical technique involves standard fixation methods using A 0 principles: ORIF using 1/3 tubular plate lateral and 3.5/ 4.0/4.5 mm screw medially. Additional stabilization consists of placement of syndesmotic screws. After surgery, non-weight bearing and cast immobilization are recommended for a minimum of 8 weeks. Casts are changed at 2 to 4 week intervals until fracture healing is evident. A removable DM CAM walker or molded plastizote lined and bivalved AFO is used with weight bearing increased 25 Ib at 2 to 4 week intervals for another 8 to 12 weeks until 75% of the patient’s weight is reached. At this time, full weight bearing is allowed. Radiographs are used before each increase in weight bearing to verify maintenance of each reduction and integrity of fixation (Fig. 7).


Figure 5. A and 6, Radiographs of a right closed supination external rotation type 4 bimalleolar equivalent ankle fracture in a 43-year-old man with type 1 diabetes mellitus with neuropathy. The patient refused recommended surgical therapy and was treated with closed reduction and a long leg cast for 10 weeks, with conversion to short leg walker use. C and 0, Six months later, symptomatic valgus malalignment of the ankle had developed, with wide medial clear space and fibula nonunion. An ankle fusion was recommended.

126 BIBBO et a1

Figure 6. A and 6, Radiographs of a supination adduction fracture of the right bimalleolar ankle fracture in a 60-year-old, dialysis-dependent woman with type 1 diabetes mellitus with neuropathy. Because she had a history of cardiac disease, she underwent nonsurgical therapy. C and 0, Radiographs 1 week later show progressive collapse with joint impaction, leading to an ankle fracture dislocation.


Figure 7. A, Radiograph of a right bimalleolar ankle fracture in a 52-year-old woman with type 1 diabetes mellitus with neuropathy who undewent surgical intervention, cast immobilization for 10 weeks (nonweightbearing), and short leg walker use for an additional 12 weeks. B, Six months later, the right ankle appears healed, with excellent alignment.

What Steps May Be Undertaken to Reduce Complications in Displaced Ankle Fractures in Patients With Diabetes Mellitus Undergoing Surgical Intervention?

A treatment protocol is crucial for the successful outcome of an intra-articular ankle fracture in a high-risk population. One must consider the fracture pattern, bone, and soft tissue quality as well as medical and social factors to determine whether a nonsurgical or surgical option is ideal to minimize the complications of the chosen treatment regimen.

Wound breakdown is one of the most common postoperative complications after a surgically treated ankle fracture. The ankle is a relatively subcutaneous joint with a high potential of complications (wound breakdown, infection) from soft tissue mismanage- ment. The soft tissue may be compromised further by the common DM factors of delayed wound healing and peripheral vascular disease.

In the emergency department, a grossly de- formed fractured ankle with the presence of

skin tenting requires emergent treatment. A delay in closed reduction and splinting may allow a closed fracture to become an open fracture with all of its attendant problems (i.e., need for emergency surgery and the higher risk for infection). The tented skin has regions of relative ischemia that progress rapidly to soft tissue necrosis. A grossly dislo- cated ankle should be reduced and immobilized emergently before obtaining radiographs to avoid any inherent delay (i.e./ waiting for film in emergency department). Early reduction may minimize the soft tissue damage.

Once the ankle fracture is reduced, the second issue becomes the relative stability of the fractured ankle in the splint. If the newly reduced ankle continues to be unstable and cannot be maintained in a splint, several op- tions exist. One option is immediate emergency surgical intervention. A better option for an unstable fracture is the emergency im- plementation of an external fixator (i.e., transarticular frame that spans the ankle joint) or calcaneal pin and traction. A patient with a closed ankle fracture, if stable in a splint or external fixator, should be treated as a semi-

128 BIBBO et a1

elective procedure, especially in a high-risk population. A closed ankle fracture grossly aligned that does not show a subluxation or dislocation of the joint and shows the absence of soft tissue and skin tenting is not considered a surgical emergency.

The timing of surgical intervention seems to be one major factor of wound breakdown. The concept of delayed staged surgical intervention is not a novel idea and has been studied extensively in another high-risk population, the high-energy pilon fracture. In- creased understanding of the issues of wound healing has led to the authors' adaptation of this delayed surgical reconstruction.

The study by Wyrsch et a195 showed the effect of surgical timing and wound complications after surgical treatment of pilon fractures. Wyrsch et a195 conducted a randomized prospective trial comparing 2 groups undergoing open reduction versus external fixation of tibia1 plafond fracture. The open reduction group had a 28% rate of infection, 33% rate of wound breakdown, and three (16%) amputations. The external fixation group had a 5% rate of skin sloughs and a 5% infection rate with no amputations.Wyrsch et a195 concluded that limited internal fixation combined with external fixation is an effective and significantly safer treatment for most fractures of the tibia plafond. A critical examination of their data reveals, however, that the 2 groups were treated in a different manner with re- gard to the timing of surgery. Most patients treated with external fixation had surgery performed at presentation (11 of 20), within hours, or after a delay of 1 week or more (7 of 20). In contrast, most patients (14 of 19) undergoing open reduction had surgery performed at 3 to 5 days, when the swelling was greatest. These latter cases experienced wound complications, which most likely were related to the timing of the surgical incision. Open reduction was done in the latter group at a high-risk period after injury. During the first week after injury, the soft tissues are marginal and cannot tolerate a surgical insult. Wyrsch's poor results in the open reduction group exemplify the importance of timing of surgery. If open reduction is to be performed, the surgery must be delayed and the soft tissue given a chance to stabilize to minimize the complications.

Two studies exemplify this issue using a staged protocol for the management of high- energy pilon fracture undergoing open reduction and plating.74, 84 Stage 1 consists of pre-

liminary stabilization (i.e., transarticular external fixator and plating the fibula). Stage 2 consists of formal pilon reconstruction. Typi- cally, 10 to 14 days is required for soft tissue stabilization. Using this protocol, Sirkin et a P reported low wound complication rates of 5.3% in all fractures and 2.9% in closed fractures. Minor wound healing problems were treated successfully with local wound care and oral antibiotics. Hospitalization was not necessary in any patients. Patterson and

used a similar protocol with equally encouraging results. The data obtained from the clinical studies of nondiabetic patients with pilon fractures can be extrapolated to diabetic patients with ankle fractures because both groups are at high risk for wound healing complication.

Based on these results, the authors advocate delaying the surgery for a minimum of 10 days (after closed reduction and splinting). The presence of skin wrinkles at the potential operative site indicates an appropriate period of delay for soft tissue stabilization. Some surgeons advocate operating within the first 8 hours after injury (when the swelling is more related to the fracture hematoma than edema). Surgical intervention may not feasi- ble with the inherent delays of the emergency department, the lack of operating room avail- ability, and the need of medical clearance (commonly seen) in a high-risk DM patient. Using the delay protocol technique, significant wound complications can be minimized.

Another common factor that must be considered is the presence of peripheral vascular disease. The association of vascular insuffi- ciency with DM has been well documented in the literat~re.4~ In the Framingham Heart Study, intermittent claudication was 3.8 and 6.5 fold more common in DM than in non-DM men and women. Theoretically a compromised circulation to the affected ankle may inhibit wound healing, despite optimizing other conditions. The authors commonly obtain a vascular consultation to optimize the situation, if possible. The presence of the fracture precludes application of the ankle brachial indices by Doppler machine. Instead, TcP02 can be used to evaluate the vascularity of the patient. A review of the literature regarding healing of the soft tissue in amputation sites of DM patients reveals a crucial TcPO, predictive value of greater than 30 mm Hg.9 An alternative technique using xenon 133 has been advocated for the measurement of skin blood f l ~ w . ~ , ~ ~ , 67 Avci and Musdo13


documented stump healing normally if the skin blood flow was greater than 1.76 mL per 100 g tissue per minute.

High-risk patients with documented poor circulation require close teamwork with a vascular surgeon before surgical intervention. Documented peripheral vascular disease (ankle brachial index, < 0.45; TcP02, < 30 mm Hg) is considered a relative contraindication unless some intervention is achieved to im- prove the circulation.

Another crucial factor regarding wound healing is the presence of active smoking. Smoking and its multiple chemical constit- uents have a detrimental effect on wound and fracture healing1, 16, 58, 93 Abidi et all documented a 33% prevalence of calcaneal skin flap wound problems after surgical intervention of calcaneal fracture using a lateral exten- sile approach. Abidi et all showed that one of the key predictive factors of increased wound healing time was active smoking preopera- tively. All DM patients should stop smoking immediately before surgical intervention.

One crucial but unquantifiable variable is compliance. Patient compliance may be mea- sured indirectly through the extent of blood glucose control or the level of hemoglobin Al,. Patients who express little interest in their glucose control or show poor control have a high risk for DM complications.30 Such non- compliant patients commonly are unavailable for follow-up or initiate their own postoperative regimen (i.e., early weight bearing), leading to catastrophic results.

The multiple issues regarding optimizing ankle fracture patients with DM can be addressed in a stepwise fashion. Through a delayed staged surgical approach, one may optimize a high-risk situation. First, the delay of 10 to 14 days allows the soft tissue to stabilize and allows for medical and surgical (vascular) evaluation and intervention, if necessary. This delay allows the patient to learn crutch training and to quit smoking before definitive treatment. The authors’ protocol was initiated to reduce the complications of surgically treated ankle fracture in patients with DM.

What Specific Type of Fixation Should Be Used in Osteopenic Bone in Patients With Diabetes Mellitus?

”[ORIF] of an ankle is an effective method- ology in maintaining alignment, and avoiding progression to Charcot neuropathic ankle de-

struction, provided A 0 principles are main- t a h ~ e d . ” ~ ~ In the series by Schon et al,79 poor outcome after ORIF of neuropathic displaced ankle fractures was attributed to inadequate reduction, suboptimal fracture fixation, or inadequate period of immobilization. The basic concept of surgical fixation of osteopenic bone is to achieve a rigid construct for increased fracture stability through concentric joint loading.43, 8o Koval et a153 advocated sup- plementing the standard fibula fixation technique with axial Kirschner wires for the management of ankle fracture in osteopenic bone (Fig. 8).60 With a cadaver model, Koval.et a153 documented an 81% increased stability using supplemental axial Kirschner wires, in addition to the plating the fibula. Torsional testing revealed that the augmented group had twice the resistance to motion than the plated group (P < 0.002). Schon and Marks57 proposed that additional fracture stability is achieved with the use of multiple fibula-tibia syndesmotic screws.

Is There a Role for Fracture Healing Adjuncts?

Several commercially available products (e.g., low-intensity ultrasound and electic stimulation) exist as fracture healing adjuncts. Although their effectiveness has been shown in accelerating fracture healing in normal pa- tientsIM no clinical series exist evaluating the effectiveness of fracture healing adjunts in patients with DM who sustain an ankle fracture. The authors currently do not use any fracture healing adjunct routinely for nonoperative or operative management of ankle fractures in DM patients. Further studies are warranted.

AUTHORS’ CLINICAL SERIES

Patients with DM who undergo a surgical intervention for an isolated displaced ankle fracture are thought to have increased complication rates compared with patients without DM. In an institutional review board- approved study, the authors compared retro- spectively the acute complication rate after surgical intervention of DM and non-DM patients with isolated displaced ankle fracture. All adult patients treated by 2 senior orthopedic surgeons (SSL, FB) between 1994 and 1998 were reviewed. Exclusion criteria included

130 BIBBO et a1

B

Figure 8. A, After manual fracture reduction, two or three 1.6-mrn Kirschner wires are inserted from the tip of the fibula across the fracture and directed to penetrate the medial cortex of the proximal fragment. B, After verification of the fracture reduction, a precontoured, one-third tubular plate is positioned on the lateral fibula cortex and stabilized with multiple screws. The screws stabilizing the distal fragment are directed to interdigitate with intramedullary wires. (From Koval KJ Jr, Petraco DM, Kummer FJ, et al: A new technique for complex fibula fracture fixation in the elderly: A clinical and biomechanical evaluation. J Orthop Trauma 11 :28-33, 1997; with permission.)

open fractures, multitrauma, preexisting infections, previous ankle pathology (i.e., preexisting osteoarthritis, Charcot joints), and follow-up of less than 3 months.

Thirteen patients with DM (group A) and 46 non-DM patients (group B) were identi- fied. The 2 groups differed regarding age (average, 55.1 in group A versus 40.2 years of age in group B). Seven of 13 patients with DM were neuropathic. Ten patients had type 1 DM, and 3 had type 2 DM. Six (46%) patients in group A developed complications (with a complication rate of 84.6% [ll complications in 6 patients]) compared with 8 (17.4%) patients in group B (with a complication rate of 26.1% [ l l complications in 8 patients]) (K0.05). Average follow-up was 46 months for group A and 32 months for group B. In the authors series, complications of group A included six superficial infections, one delayed union, and one deep infection (osteomyelitis). The superficial infection re- solved with oral antibiotics. Three patients developed Charcot arthropathy, but two in- stances occurred in patients with a delay of diagnosis or lack of appropriate immobilization (average time of the emergency department presentation was 13 days after fracture).

A third patient who developed Charcot arthropathy had concurrent complication of deep infection. All three patients were treated successfully with DM AFO bracing. The patient with deep infection was treated successfully with 6 weeks of parenteral antibiotic followed by an oral antibiotic regimen for 3 months. There was no loss of limb or ankle arthrodesis in this limited series. Patients with DM do have an increased complication rate after surgical fixation of isolated ankle fractures compared with non-DM patients; nevertheless, most problems are handled easily without significant morbidity.

SUMMARY

Ankle fracture in patients with DM man- dates a stepwise protocol to minimize the potential complications of delayed fracture healing, wound complications, and development of Charcot arthropathy. For nondisplaced ankle fracture, a nonoperative approach with increased duration of immobilization seems successful based on experience of the limited series. A displaced ankle fracture in a patient with DM requires a surgical intervention. The


authors advocate tight glucose control in both PUPS to hprove *e fracture milieu and ‘0 ameliorate the potential complications. Appro- priate stable fixation with adequate length of immobilization is crucial for successful frat-

patterns of radiographic change. Foot Ankle 4:15- 22,1983

18. connol1y F, Csencsitz TA: Limb threatening neuropathic complications from ankle fractures in patients with diabetes. Clin Orthop 384212-219,1998

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complications of ankle fractures in diabetic patients

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