Diabetic foot osteomyelitis: Bone markers and treatment outcomes.
ABSTRACT Novel bone turnover markers could help with the diagnosis and monitoring of osteomyelitis patients. We compared levels of two bone turnover markers, serum amino-terminal telopeptides (NTx) and bone alkaline phosphatase (BAP), in diabetic patients with and without osteomyelitis.
Matched case-control study was conducted with diabetic patients with and without osteomyelitis. Cases not undergoing immediate amputation were followed with repeat measurements after osteomyelitis treatment and for outcome determination.
Analysis included 54 subjects, 27 cases and 27 controls. Median BAP levels were similar between cases and controls at enrollment (p=.55) as were median NTx levels (p=.43). Cases with follow-up data (n=18) had similar bone marker levels at enrollment and 6 weeks. No significant differences in BAP or NTx levels at enrollment or follow-up were seen between cases with poor versus favorable outcomes.
No differences in NTx or BAP levels were seen between cases and controls. Cases with follow-up data had similar levels at enrollment and 6 weeks. Lack of difference may be due to small sample size, small areas of bone involved in foot osteomyelitis, or limitations of these specific markers. More research is needed.
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ABSTRACT: Histological and molecular analysis of fracture healing in normal and diabetic animals showed significantly enhanced removal of cartilage in diabetic animals. Increased cartilage turnover was associated with elevated osteoclast numbers, a higher expression of genes that promote osteoclastogenesis, and diminished primary bone formation. Diminished bone formation, an increased incidence of nonunions, and delayed fracture healing have been observed in animal models and in patients with diabetes. Fracture healing is characterized by the formation of a stabilizing callus in which cartilage is formed and then resorbed and replaced by bone. To gain insight into how diabetes affects fracture healing, studies were carried out focusing on the impact of diabetes on the transition from cartilage to bone. A low-dose treatment protocol of streptozotocin in CD-1 mice was used to induce a type 1 diabetic condition. After mice were hyperglycemic for 3 weeks, controlled closed simple transverse fractures of the tibia were induced and fixed by intramedullary pins. Histomorphometric analysis of the tibias obtained 12, 16, and 22 days after fracture was performed across the fracture callus at 0.5 mm proximal and distal increments using computer-assisted image analysis. Another group of 16-day samples were examined by microCT. RNA was isolated from a separate set of animals, and the expression of genes that reflect the formation and removal of cartilage and bone was measured by real-time PCR. Molecular analysis of collagen types II and X mRNA expression showed that cartilage formation was the same during the initial period of callus formation. Histomorphometric analysis of day 12 fracture calluses showed that callus size and cartilage area were also similar in normoglycemic and diabetic mice. In contrast, on day 16, callus size, cartilage tissue, and new bone area were 2.0-, 4.4-, and 1.5-fold larger, respectively, in the normoglycemic compared with the diabetic group (p < 0.05). Analysis of microCT images indicated that the bone volume in the normoglycemic animals was 38% larger than in diabetic animals. There were 78% more osteoclasts in the diabetic group compared with the normoglycemic group (p < 0.05) on day 16, consistent with the reduction in cartilage. Real-time PCR showed significantly elevated levels of mRNA expression for TNF-alpha, macrophage-colony stimulating factor, RANKL, and vascular endothelial growth factor-A in the diabetic group. Similarly, the mRNA encoding ADAMTS 4 and 5, major aggrecanases that degrade cartilage, was also elevated in diabetic animals. These results suggest that impaired fracture healing in diabetes is characterized by increased rates of cartilage resorption. This premature loss of cartilage leads to a reduction in callus size and contributes to decreased bone formation and mechanical strength frequently reported in diabetic fracture healing.Journal of Bone and Mineral Research 05/2007; 22(4):560-8. · 6.13 Impact Factor
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ABSTRACT: Osteomyelitis of the foot, a common and serious problem in diabetic patients, results from diabetes complications, especially peripheral neuropathy. Infection generally develops by spread of contiguous soft-tissue infection to underlying bone. The major diagnostic difficulty in diabetic patients is distinguishing bone infection from noninfectious neuropathic bony lesions. Certain clinical signs suggest osteomyelitis, but imaging tests are usually needed. The 111In-labeled leukocyte scan and magnetic resonance imaging are the most diagnostically useful. Staphylococcus aureus is the most common etiologic agent, followed by other aerobic gram-positive cocci. Aerobic gram-negative bacilli and anaerobes are occasionally isolated, often in mixed infections. Antimicrobial therapy is best directed by cultures of the infected bone, obtained percutaneously or at surgery. Antibiotic therapy should usually be given parenterally, at least initially, and continued for at least 6 weeks. Surgical debridement or resection of the infected bone, when feasible, improves the outcome. With appropriate therapy most cases of osteomyelitis can be successfully managed.Clinical Infectious Diseases 01/1998; 25(6):1318-26. · 9.37 Impact Factor
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ABSTRACT: We assessed the diagnostic value of swab cultures by comparing them with corresponding cultures of percutaneous bone biopsy specimens for patients with diabetic foot osteomyelitis. The medical charts of patients with foot osteomyelitis who underwent a surgical percutaneous bone biopsy between January 1996 and June 2004 in a single diabetic foot clinic were reviewed. Seventy-six patients with 81 episodes of foot osteomyelitis who had positive results of culture of bone biopsy specimens and who had received no antibiotic therapy for at least 4 weeks before biopsy constituted the study population. Pathogens isolated from bone samples were predominantly staphylococci (52%) and gram-negative bacilli (18.4%). The distributions of microorganisms in bone and swab cultures were similar, except for coagulase-negative staphylococci, which were more prevalent in bone samples (P < .001). The results for cultures of concomitant foot ulcer swabs were available for 69 of 76 patients. The results of bone and swab cultures were identical for 12 (17.4%) of 69 patients, and bone bacteria were isolated from the corresponding swab culture in 21 (30.4%) of 69 patients. The concordance between the results of cultures of swab and of bone biopsy specimens was 42.8% for Staphylococcus aureus, 28.5% for gram-negative bacilli, and 25.8% for streptococci. The overall concordance for all isolates was 22.5%. No adverse events--such as worsening peripheral vascular disease, fracture, or biopsy-induced bone infection--were observed, but 1 patient experienced an episode of acute Charcot osteoarthropathy 4 weeks after bone biopsy was performed. These results suggest that superficial swab cultures do not reliably identify bone bacteria. Percutaneous bone biopsy seems to be safe for patients with diabetic foot osteomyelitis.Clinical Infectious Diseases 01/2006; 42(1):57-62. · 9.37 Impact Factor