Biochemical and ultrasound tests for early diagnosis of active neuro-osteoarthropathy (NOA) of the diabetic foot

Diabetes Res Clin Pract. 2002 Oct;58(1):1-9. doi: 10.1016/s0168-8227(02)00097-9.


Objectives: To test the effectiveness of a combined approach to an early diagnosis of neuro-osteoarthropathy (NOA) of the diabetic foot, we studied a group of outpatients with active NOA, presenting for the first time to our Diabetic Foot Clinic in 1998, by means of an integrated approach designed to assess bone turnover.

Patients and methods: Fifteen consecutive diabetic patients (five Type 1 and ten Type 2 diabetic individuals, age 61.9+/-12.2 years, diabetes duration 18.7+/-8.9 years, HbA(1c) 8.4+/-1.5%) with active NOA (Group 1) were compared to nine diabetic patients with chronic stable NOA (Group 2), 14 neuropathic diabetic patients without NOA (Group 3), 13 non-neuropathic diabetic patients (Group 4) and 15 healthy controls (Group 5). Determination of serum carboxy-terminal collagen telopeptide (ICTP), bone alkaline phosphatase isoenzyme (B-ALP), osteocalcin (BGP) concentrations, as well as urinary excretion of deoxypyridinoline (DPD) were obtained in all individuals for assessment of bone reabsorption and new bone formation. Moreover in all individuals quantitative ultrasound (QUS) of the calcaneal bone was performed and mass density of lumbar spine and femur bone was determined by dual-energy X-ray absorptiometry (DEXA).

Results: QUS was significantly lower in the active NOA patients as compared with other groups (P<0.01), while ICTP was higher in both NOA groups (P<0.01). Urinary DPD was higher in the neuropathic non-NOA group (P<0.01) than the other groups, and osteocalcin was higher in healthy controls compared to diabetic patients without NOA. QUS and ICTP were inversely correlated (r=0.44, P=0.000). QUS in the active NOA group was significantly (P<0.01) lower in the affected compared to the unaffected foot.

Conclusion: Our results indicate a possible role for an integrated approach to the diagnosis and monitoring of NOA involving the diabetic foot. DPD may identify patients at-risk for NOA, ICTP could be tested as a marker for NOA in asymptomatic cases. Finally, QUS of the calcaneal bone may be useful in discriminating active versus quiescent phases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Body Mass Index
  • Bone and Bones / metabolism*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Foot / diagnosis*
  • Diabetic Neuropathies / diagnosis*
  • Diabetic Neuropathies / diagnostic imaging
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Middle Aged
  • Osteoarthritis / diagnosis*
  • Osteoarthritis / diagnostic imaging
  • Outpatients
  • Reproducibility of Results
  • Ultrasonography


  • Glycated Hemoglobin A