New Use of Old Technology Could Aid Diabetic Foot Disease

Nancy A. Melville

August 12, 2013

A novel use of an old technology could help earlier diagnosis of osteomyelitis in the feet of diabetic patients, which in turn could lead to better treatment and perhaps fewer amputations in the long run, a new feasibility study published online August 6 in Diabetes Care has shown.

The researchers identified early changes in bone composition with the use of Raman spectroscopy in 17 patients with a clinical diagnosis of osteomyelitis in their feet requiring surgical intervention.

The distinctive presence of dicalcium phosphate dihydrate, known as brushite, and uncarbonated apatite appeared to be uniquely associated with infected areas of bone, say Blake J. Roessler, MD, from the University of Michigan Medical School's division of metabolism, endocrinology, and diabetes, Ann Arbor, Michigan, and colleagues.

"The goal would be more accurate or rapid diagnosis in a point-of-care environment with a cost point that would be much less than CT or MRI," said Dr. Roessler. "We think there could be value streams in terms of better utilization of antibiotics and surgical interventions for diabetic patients."

Next Step to Develop Commercial Equipment

The researchers developed a portable bedside instrument using Raman spectroscopy, which has been employed for nearly a century for applications ranging from material science to pharmaceutical uses. Raman spectroscopy relies on scattering of monochromatic light and interaction with phonons, revealing patterns in the physical chemistry of the target.

They examined bone specimens from the patients, six of whom were undergoing surgical intervention to collect a bone biopsy specimen and 11 of whom were undergoing amputations.

They identified brushite as being uniquely associated with infected areas of bone.

"The discovery wasn't entirely unexpected, because brushite has been identified in dental plaque, so there is existing literature showing it to be associated with bacterial biofilms," said Dr. Roessler.

Aside from its presence in dental plaque, brushite has previously been found in vivo only under chronically acidic conditions such as urinary stones and chondrocalcinosis, the authors explain.

Bacterial biofilm is likely to have generated the acidic environment necessary to form brushite, rather than the latter being the result of an inflammatory or immune response or excessive bone remodeling, they note.

Only 1 other study has documented brushite in mature human bone — in fibrous dysplasia of the jaw, they add.

The novel finding suggests that mineralization could represent an important compositional marker of the type of early-stage bone infection that characterizes diabetic osteomyelitis.

Importantly, such compositional changes cannot be detected via standard diagnostic imaging or histopathology, underscoring the value of Raman spectroscopy.

"We're really in the translational stage now," Dr. Roessler said. "Our intended next step would be to develop commercial equipment with some modifications to try to conduct some longitudinal clinical trials in a point-of-care context."

The study received funding from the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Biomedical Imaging and Bioengineering. The authors have reported no relevant financial relationships.

Diabetes Care. Published online August 6, 2013. Abstract

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