Different from hematogenous osteomyelitis, the occurrence of DFO is mainly caused by the continuous invasion of bacteria in the infected soft tissue into the bone through bone exposure or fistula formed by diabetic foot ulcers. It mainly involves the weight-bearing parts of the foot (16). The development of diabetic foot is the result of a combination of peripheral vascular disease, diabetic peripheral neuropathy (DPN), and infection. DPN plays a major role in the etiology of diabetic foot, affecting the function of motor, sensory, and autonomic nerves. This not only leads to the loss of pain, temperature, pressure, and other protective sensations, but also leads to foot trauma and subsequent infection due to the undue pressure exerted on the feet without the patient's knowledge. Additionally, peripheral vascular diseases lead to poor blood supply which results in local drug concentrations that are ineffective against invading bacteria at the local region of infection. Infection then occurs once the bacteria invade and colonize. Healing becomes difficult if the above mentioned conditions are met. For the management of DFO, anti-infection and stabilization of the foot are the most important factors. Studies have shown that the effects of systemic antibiotics and traditional surgery on DFO are very limited. Adjunctive treatment of such infections with the use of local antibiotic delivery systems has shown improved outcomes (17).
Antibiotic bone cement was first used by Buchholz in 1970 (15), and since then, it has been commonly used as an effective adjuvant therapy for chronic infection, traumatic osteomyelitis, and nonunion (15, 18). Compared to systemic administration, local antibiotic therapy can avoid systemic adverse reactions with a longer duration and more accurate positioning (4). Possible residual bacteria post debridement could be killed by high concentrations of antibiotics released locally, for which the effective concentrations might be 1000 times that of systematic antibiotics. However, the dose of local vancomycin that passes into circulation is far less than that from systematic administration resulting in a mild presentation of adverse reactions. Conversely, it is not affected by ischemia of the limb as it acts directly at the lesion site. Additionally, the residual dead space post debridement can be filled with bone cement shaped properly in order to decrease the recurrence of infection and provide some leeway space, in the case of contracture of the skin margin. Recently, Li et al. investigated the role of induced membrane (IM) using antibiotic bone cement; they found that IM assisted the wound healing by promoting angiogenesis (19).
Currently, local drug-loading sustained-release systems can be divided into biodegradable and non-biodegradable systems. Although biodegradable sustained-release systems have been an attractive treatment option in recent years, most have been used in animal studies. Therefore, polymethylmethacrylate (PMMA), a representative of non-degradable materials, has remained the standard for sustained-release carriers in the clinic. In this study, PMMA was chosen as the carrier because PMMA pellets can provide immediate stabilization or assist in maintaining the stabilization of the bone tissue structure. Additionally, it is beneficial to maintain the length of the bone and soft tissue in the area with the bone defect after debridement of the chronic osteomyelitis infected lesions, and to provide a good bone graft space and bed for the bone graft reconstruction of stage II bone defects.
For the treatment of osteomyelitis infection, it is critical to choose effective antibiotics. Although the distribution of pathogenic bacteria in DFO wounds has changed over the years, Staphylococcus aureus remains the most common infecting organism (20), as observed in the current study. More remarkably, the occurrence of multidrug-resistant organism isolation increases annually. MRSA as the most important of these pathogens, has been associated with a significantly higher rate of treatment failure in patients with diabetic foot infections (21). Vancomycin is a glycopeptide antibiotic, which has good antimicrobial activity against G + bacteria, especially for the treatment of MRSA. Additionally, the release curve of this drug in bone cement is stable, proving its stability to heat and its water-solubility.
In this study, DFO was treated using comprehensive interventions, including VSD and flap transplantation, instead of just a single application of antibiotic-loaded bone cement. VSD is reportedly safer and more effective than traditional treatments for patients with DFO (22). Complete drainage can be achieved under negative pressure (23); bacteria, pus, and exculpated necrotic tissue in the drainage area can be periodically and thoroughly drained from the body, and in the process the wound is kept completely clean. Furthermore, VSD reduces the degree of inflammation and improves phantom limb edema by reducing vascular permeability through aspiration. Conversely, the application of VSD in the negative pressure state can significantly expand the blood vessel diameter, improve blood flow velocity and blood flow, slightly promote capillary regeneration, and improve the partial pressure of oxygen in the foot tissue. In our study, antibiotic bone cement combined with VSD was used after complete debridement, and skin grafting or flap transplantation was performed in the second stage after the wound surface was stabilized. The average duration of treatment with antibiotics was 23.0 days and the average time in which ulcers healed was 37.8 days; these findings were shorter than those reported in some studies (24). All the cases in our study were cured and no amputations above the ankle were required. Based on the Maryland criteria, the excellent-good rare was 72%.
It is essential that comprehensive treatments control basic diseases for a sustained duration. In our experience, only the basic conditions are well-regulated if the patients can tolerate surgery and if the surgical outcomes can be sustained for long periods. Wounds should not be covered with tensile force or slap to avoid the injuries associated with ischemia in microcirculation. Skin grafting is sometimes possible. The use of customized and fitted orthopedic shoes with soft soles could disperse the pressure under the foot and improve the weight-bearing abilities in the lower limbs after the wound has healed. Exercises focused on protected function could improve the quantity of life and reduce the risk of amputation. However, not all patients can persist wearing the orthopedic shoes. Regular follow-up and coordination among patients’ family members might assist them in avoiding the condition.