Tissue Volumizing: Can We Create An Internal Orthotic?

     The rapid rise in the incidence of diabetes, a serious lifelong condition, is of alarming concern to healthcare professionals. Recent data from the Centers of Disease Control and Prevention (CDC) estimate that approximately 20.8 million people, roughly 7 percent of the United States population, have diabetes.1 In 2005 alone, 1.5 million new cases of diabetes were diagnosed in people aged 20 years or older.1 Diabetes mellitus is a multifaceted disease and foot ulceration, which often results in lower extremity amputations, is one of the most common complications.2-5      The lifetime risk of a person with diabetes developing a foot ulcer has been estimated at 15 percent.6 However, recent studies have shown the annual population-based incidence ranges from 1.0 to 4.1 percent and the prevalence ranges from 4 to 10 percent, suggesting the incidence may be as high as 25 percent.3 Diabetic foot ulcers frequently become infected and are a major cause of hospital admissions.4,5 They also account for more than half of non-traumatic lower limb amputations in this patient population.4 Diabetic foot ulcers impose tremendous medical and financial burdens on our healthcare system with costs conservatively estimated up to $45,000 per patient. These estimates, however, do not include the deleterious psychosocial effects on the patient’s quality of life because of impaired mobility and substantial loss of productivity.8-11      The etiology of foot ulcerations in people with diabetes is generally associated with the presence of peripheral neuropathy and cycles of repetitive stress generated by normal ambulatory activities.12 During ambulation, the foot is exposed to moderate or high pressure and shear forces. Foot deformities, limited joint mobility, partial foot amputations and other structural deformities often predispose patients with diabetic peripheral neuropathy to abnormal weightbearing, areas of concentrated pressure and abnormal shear forces that significantly increase their risk of ulceration.13-15 Patients with previous foot ulcerations can withstand fewer cycles of stress to their feet before reulcerating.16 Peripheral neuropathy is usually profound before leading to a loss of protective sensation (LOPS). The consequent vulnerability to physical and thermal trauma thereby increases the risk of foot ulceration sevenfold.17-18      In one study of patients with peripheral neuropathy, 28 percent with high plantar pressure developed a foot ulcer during a 2.5 year follow-up, compared to none with normal plantar pressure.19 The frequency, magnitude and duration of forces to the plantar aspect of the foot comprise the etiologic criteria to assess ulcer formation and consider strategies to prevent and heal plantar foot ulcerations.12 Subsequently, many studies have linked plantar pressures to the sites of ulceration in neuropathic patients.20-23

Can A Tissue Volumizing Agent Redistribute Plantar Pressure?

     The present tenet for preventing wounds therefore focuses on the redistribution of pressure. One would customarily do this with therapeutic footwear and accommodative orthotics. The ability to easily remove prescribed footwear eliminates the element of “forced adherence.” A study that evaluated the activity of patients with diabetic foot ulcerations and adherence to their pressure offloading device noted that patients wore their prescribed offloading modality for only 28 percent of their total daily activity.24      The data reported above may be explained at least partially by another study conducted in patients with diabetes who are at high risk for foot amputation. In an evaluation of the magnitude and location of activity of people with diabetes in this high-risk population, results suggested that patients may be at least as active at home as they are outside their home.25 While 85 percent of the patients in that study indicated that they wore their physician-approved shoes most or all of the time while outside the home, only 15 percent continued use of the shoes while at home.25 It may therefore be postulated that patients with neuropathic ulcers who wear removable offloading devices may perceive the home environment as safe and be less adherent to wearing their devices.      By injecting a tissue volumizing agent beneath a plantar prominence, it may be possible to create an internal accommodative orthotic effect that follows the patient everywhere he or she goes, and acts to mitigate pressure 24 hours a day. Accordingly, tissue augmentation may have the benefit of adequate offloading as well as adding an element of “forced compliance” to the prescribed course of pressure reduction. Further, patients may also benefit from certain prophylactic interventions, including evaluation for surgical interventions to alter their biomechanics and loading.      It has been well established that plantar pressure is directly proportional to plantar tissue thickness.26,27 Fat pad atrophy is common among people with diabetes, particularly in the forefoot.28,29 Clearly, augmenting this high-risk area with a biocompatible, viscoelastically robust substance might have the benefit of mitigating pressure and potentially reducing the risk for ulceration. Researchers, who have studied the use of substances such as silicone in the foot, suggest there is significant improvement in soft tissue thickness and subsequent profound reduction in plantar pressure.

What The Research Reveals About Silicone Injections

     Sol W. Balkin, DPM, who reportedly has the most experience with silicone foot injections in the U.S., reported on 1,439 silicone injected patients.30-33 Thirty-eight patients had diabetic neuropathy with 41 ulcers and 16 pre-ulcerative lesions. The patients received injections of silicone in doses of 0.10 to 0.25 mL at the site of ulceration or plantar prominence at one- to four-week intervals to a mean total of 1.65 mL. All 41 ulcers healed initially while 30 (73 percent) remained healed at a mean follow-up of 6.3 years. None of the 16 pre-ulcerative lesions recurred. There were no reports of infection, rejection or allergy.      Balkin and colleagues obtained postmortem specimens from deceased patients (unrelated mortality) and evaluated them at a mean of 14 years (range of one to 29 years) post-silicone implantation. Histological analysis of these specimens revealed noninflammatory fibrosis and histiocytic phagocytosis. In rare instances, asymptomatic fluid migration occurred and required surgical removal.      In the United Kingdom, Van Schie, et. al., performed a randomized, double-blind, placebo-controlled (saline) trial on 28 diabetic neuropathic patients with high peak plantar pressures under metatarsal heads.29 Peak plantar pressures were reduced by 232 kPa in the silicone group and by only 25 kPa in the saline group. The researchers found that plantar soft tissue thickness, measured by ultrasound, increased by 1.8 mm in the silicone treated group versus 0.1 mm in the control group.      Unfortunately, in the U.S., availability/production and medical legal concerns have made silicone a less than realistic choice for implementation in a widespread setting. Other products, such as poly-L-lactic acid and hyaluronan, have shown promise as fat pad replacements/dermal fillers.34,35 Poly-L-lactic acid appears to have direct promise in this regard as its current primary indication is for facial lipoatrophy commonly associated with the human immunodeficiency virus (HIV).

A Closer Look At Injectable Agents

     Due to the increased demand for minimally invasive techniques, the use of injectable agents, specifically soft tissue fillers, for treatment of the aging face has increased dramatically in recent years. In fact, they currently represent the most commonly performed cosmetic procedures in the U.S. Selecting an appropriate filler requires knowledge of the available materials and an understanding of their properties.      Hyaluronic acid is a popular filler used by plastic surgeons for temporary augmentation of lips, wrinkles and folds. Hyaluronic acid is a mammalian polysaccharide found naturally in the dermis. Hyaluronic acid is biodegradable. It will eventually degrade and be eliminated, and requires repeat injections every four to six months.      In one study, researchers clinically evaluated the hyaluronic acid derivative Restylane™ (Medicis Aesthetics) in 100 patients receiving injections into 285 facial wrinkles. Physicians reported the degree of correction to be 82 percent at three months and 66 percent at one year. All of the patients showed approximately 60 percent of the original effect. Side effects reported included erythema but there were no serious or permanent adverse events noted.35      Bovine collagen is a commonly used, nonpermanent dermal filler. It is easily accessible and has a safe profile. However, because it is an animal protein, up to 5 percent of the population may develop a hypersensitivity reaction.      Radiesse (Bioform Medical), formerly marketed as Radiance, is the first calcium hydroxylapatite injectable cohesive implant used for soft tissue augmentation. It has been used by the medical field for over 25 years and consists of microspheres of calcium hydroxylapatite suspended in a biocompatible carboxymethylcellulose gel.      After injection, these microspheres stimulate natural collagen growth to produce longer lasting results. Calcium hydroxylapatite may be an effective alternative for patients wishing to avoid the potential side effects of bovine and solid implant materials. It is long lasting (up to two years) and does not require a skin test since calcium hydroxylapatite is found in our bones and teeth. Radiesse is also approved in the U.S. to treat oral and maxillofacial defects, and vocal cord deficiencies.      Injectable poly-L-lactic acid (Sculptra™, Sanofi Aventis) is an injectable implant that contains microparticles of poly-L-lactic acid, a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family. Polylactic acids have a longstanding history of safe use in medical applications and have been widely used for many years in dissolvable sutures, soft tissue implants and biodegradable internal fixation. Sculptra is reconstituted prior to use by the addition of sterile water and local anesthetic for injection in order to form a sterile non-pyrogenic suspension.      A current literature review reveals the lack of any reports evaluating poly-L-lactic acid in the diabetic foot. While no literature is available evaluating the use of this substance for foot augmentation, 61 immunocompromised, HIV-infected male patients (52 Caucasians, seven African-Americans, one Latino and one Asian) underwent multiple treatment sessions with PLLA over a five-month period for facial lipoatrophy. There were no reported cases of infection, allergies or serious adverse reactions, and the treatment was well tolerated.      All transcutaneous procedures carry a risk of infection and patients treated with anticoagulants may run the risk of a hematoma or localized bleeding at the injection site. Acute complications are usually caused by the injection procedure itself or the material being injected. Some possible complications include bruising, edema, discomfort, inflammation, fever, erythema, injection site tenderness, lesion formation and induration. The most common complication for facial PLLA injection is the delayed formation of subcutaneous papules, which are typically confined to the injection site, palpable, asymptomatic and invisible.      One should instruct patients to minimize excessive sun or UV lamp exposure of the treatment area until any initial swelling and redness has resolved. Delayed complications are rare and include migration of the material and scarring.

Final Words

     Scholl’s Center for Lower Extremity Ambulatory Research (CLEAR) is currently conducting a trial on 80 patients with diabetic neuropathy with pre-ulcerative callus under metatarsal heads or the hallux for randomization and injection of either PLLA (Sculptra) or placebo. Patients will receive three injections spaced two weeks apart. Researchers will follow them for 12 months and record dynamic plantar pressure pre- and post-treatment. These data will be compared to the van Schie data on silicone injections in diabetic feet to determine if there are any medium or long-term effects.29      Soft tissue augmentation of the high-risk plantar diabetic foot with fillers may soon be a promising prophylactic technique to increase plantar soft tissue thickness and create an internal orthotic effect that can ultimately reduce the risk for ulceration. The results of this randomized controlled study will help assess the biocompatibility of dermal fillers in the plantar foot and their efficacy in pressure mitigation and ulcer prevention. Dr. Wu is the American Podiatric Medical Association Senior Fellow at the Center for Lower Extremity Ambulatory Research (CLEAR) at the William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in Chicago. Dr. Rogers is a Research Fellow at the Center for Lower Extremity Research (CLEAR) at the William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science. Dr. Bevilacqua is a Research Fellow at the Center for Lower Extremity Research (CLEAR) at the William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science. Dr. Armstrong is a Professor of Surgery, Chair of Research and Assistant Dean at the William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine in Chicago. He is the Director of the Center for Lower Extremity Ambulatory Research (CLEAR) at the aforementioned university and is the Co-Chair of the Diabetic Foot Global Conference (DFcon.com). For further reading, check out the archives at www.podiatrytoday.com.
 

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