The chronic hyperglycemia of diabetes, a highly widespread chronic disease, is associated with long-term damage, dysfunction, and failure of various organs. In particular, patients experience neuropathy and blood vessels degeneration. These two complications develop into the foot disease which alters the biomechanics of gait and eventually leads to the formation of callosity and ulcerations.

The social and economic burden of the diabetic foot can be reduced through early diagnosis and treatment. Diabetic neuropathy is present in 25% of the patients after 10 years of disease, and it is the most significant risk factor for the development of foot ulcers. It consists in the distal symmetrical polyneuropathy which affects the motor and sensitive systems, both involved in the pathogenesis of the diabetic foot 1. The motor sensitivity deficit exposes the patient to the risk of ulcers 2. In addition, motor neuropathy leads to the degeneration of intrinsic foot muscles (lumbrical and interosseous) that cause deformation of the metatarsal heads and, in turn, excessive plantar loads during gait that predispose to callus formation, hyperkeratosis and ulcers 3. Callus formation is associated with biomechanical foot dysfunction especially abnormal subtalar joint pronation 4.

Given this scenario, it is of paramount importance to study diabetic foot biomechanics in order to assess the risk of ulceration. These patients exhibit a displacement of the fulcrum of the step from the tibio-tarsal to the coxo-femoral joint, and an increase of the base of support with ataxic posture together with posture modifications 5678. The additional alterations of the soft tissues, tendons and the ligaments lead to a further limited joint mobility occurring especially to 1^st metatarsophalangeal and subtalar joints 4. In particular the plantar fascia behaves like one rigid lever during the step, reducing the adaptability to the ground 9101112.

The study of structure and function of the diabetic foot have received little attention in the literature, while most of the studies have concentrated on the kinetic analysis by means of force and plantar pressure plates 456789101112. On the other hand kinematic analysis would be clinically very important for diabetic neuropathic patients in order to appreciate the supination-pronation and inversion-eversion movement of forefoot vs midfoot and hindfoot. Unfortunately, currently available movement analysis protocols 13141516 are not suitable for this purpose. These procedures, which utilize rigid mounting plates by means of elastic bandages and lengthy anatomical calibration procedures 13141517, cannot be easily applied in patients with peripheral artery disease or neuropathies. Protocols which consider the foot as a single rigid segment or does not consider the motion of the midfoot relatives to the adjacent subsegments cannot fully describe the diabetic foot disease consequences 1314151617181920202122. Therefore direct skin marker placement on selected anatomical landmarks (ALs), was chosen, together with a 3D four segments foot kinematics protocol. A static acquisition was used to define the anatomical Bone Embedded Frames (anatomical BEFs). Diabetic patients frequently have rigidity of toes or presence of ulcers which make protocols requiring marker placement on hallux impossible 1318192122. Moreover, the most recent studies 192122 do not report all three rotational degrees of freedom of the three relevant foot sub-segments. Foot biomechanics alteration in the neuropathic patients 4 affects also their posture 623, this entails that a foot motion analysis protocol must be incorporated in a full body gait analysis protocol 15161720242526. Finally, no study has reported on the clinical impact of foot kinematic analysis in diabetic patients 131418192122.

The objective of this study was to devise a reproducible and clinically meaningful protocol 25 specific for the treatment of diabetic patients, which starting from the kinematics could help in preventing diabetic foot from ulcer or callus formation.

Experiments were carried out using a six camera stereophotogrammetric system (BTS, Italy) with a sampling rate of 60 frames per second synchronized with two Bertec force plates (FP4060-10). Force plates were used to determine the gait cycle parameters (time and space). Ten healthy subjects and ten diabetic neuropathic subjects were analyzed (see Table 1). The healthy subjects did not have any metabolic, cardiovascular and neurological disease. Neuropathic diabetic subjects were recruited among the outpatients of the Antidiabetic Unit of the University Hospital of Padova, Italy. All volunteers were asked to sign an informed consent form.

Even though various biomechanical models have been developed so far to study the properties and behaviour of the foot 1418192122, the present study focuses on developing a methodology for the functional assessment of the foot-ankle complex and for the definition of a functional model of the diabetic neuropathic foot.

A method for capturing forefoot, midfoot and hindfoot motion during different gait tasks have been proposed. The model includes tibia and fibula, hindfoot, midfoot and forefoot, and allows investigation of 3-dimensional foot and ankle kinematics through stereophotogrammetry. A new model has been generated since available foot protocols were not suitable for this type of analysis 1819212226. One important limitation of the literature was that the 3 planar motion of the midfoot was not evaluated. As the diabetic foot disease accounts for midfoot structural polymorphism which commonly leads to plantar ulceration 3435, the authors believe that a suitable model to describe the diabetic foot biomechanics should perform 3D midfoot kinematic analysis. Furthermore, this was confirmed by the results reported in Figure 3 where, the diabetic group has statistically significant differences in midfoot kinematic parameters over a large part of the gait cycle. Nevertheless the forefoot should be considered entirely and not represented by a single toe as the hallux 36 because it is considered the high risk zone for plantar ulcer formation 436. This was confirmed by the results reported in Figure 3 where, the diabetic group showed statistically significant differences in forefoot kinematic parameters over the full gait cycle in the sagittal and coronal planes, and in the 50% of gait cycle in the transversal plane. Furthermore in the literature has been reported that in diabetic patients, changes in weight bearing patterns are linked to limited joint mobility that occurs mostly at metatarsophalangeals and subtalar joints. Nevertheless the location of forefoot plantar ulcers in diabetic subjects has been demonstrated to be highly correlated with rearfoot alignment 4. In addition to the different types of mechanisms of excessive pressure loading, abnormal alignment of the foot also affects pressure loading on the foot. Finally patients with an uncompensated forefoot varus or forefoot valgus (inverted or everted forefoot) had ulcers located at the first or fifth metatarsal head. Similarly, an inverted heel position has been associated with lateral ulcers, whereas an everted heel position has been associated with medial ulcers 36. So far the authors believe that a technique for the measurement of rearfoot-forefoot-midfoot structures alignment is needed in understanding the aetiology of diabetic foot ulcers. Finally, the triplanar orientation of the joint axis allows for movement in all three body planes and thus provides a mechanism for compensatory motion if there is presence of structural anomalies in the foot 4, which is indeed the case of the diabetic foot.

Protocols which adopt rigid array of markers and procedures which implies calibration techniques 131415 where not adopted because they present as major disadvantage the time required for each anatomical landmark calibration trial. Furthermore when errors due to skin artefacts affect protocols using mounting plates, it is difficult to identify the relative contribution of each individual marker, as the errors affect the complete cluster as a whole. Therefore we choose direct skin marker placement on ALs even though these are more subject to errors due to skin artefacts and markers misplacement 26. An extensive review of the problem is given in Leardini et al. 2005 37. This protocol tries to prevent these errors by using the above described algorithm with a static calibration and by controlling for markers occlusion.

The ALs were selected in order to be easily palpated and identified. The location of the ALs was chosen so that BEFs were directly defined with no need of technical frames definition 15.

As suggested by Baker 26 a foot model have been applied to a pathologic population, even though in this specific case one of the existing models could not be adopted as was previously done by Woodburn 38 for the reasons reported above. In the present work, ten neuropathic subjects have been evaluated and results of this analysis showed major statistically significant differences between the two populations both in the forefoot vs midfoot and midfoot vs hindfoot dorsi-plantarflexion (100% of frame of the gait cycle). Also important statistically significant differences were observed in midfoot vs hindfoot internal-external rotation (90% of frame of the gait cycle), in forefoot vs midfoot inversion-eversion, in ankle internal-external rotation (96% of frame of the gait cycle) and inversion-eversion (92% of frame of the gait cycle). Thus to confirm the validity of a similar approach in order to assess diabetic neuropathics' biomechanics impairment.

An important step in assessing the effectiveness of gait analysis is to establish the precision of the data collection 32 and the accuracy in determining the anatomical landmarks and joint embedded frames definition. An effort in this direction is documented in Table 2 and 3 were a detailed description of ALs, and BEFs together with instruction for marker placement can be found. It is, of course, important to evaluate the major sources of variation in gait analysis (true variation in the subject's gait and artefact from the measurement procedure) 32. We therefore need an estimate of the expected variability in joint rotation angles estimation. This is important when, for example, comparing a patient data against normative standards - we need to know how much difference is significant. Normal biological variation affects kinematics data since subjects never walk in the exact same way in every trial, therefore variability introduced by the subject within a test session were examined. Variability is also introduced by the measurement procedure by means of anatomical landmarks identification and skin movement artefact. Therefore joint rotation angles variability due to differences between clinicians, and by the subject within and between test days were examined 303132. Three walking trials per subject were acquired together with a static acquisition. The same procedure was applied both to normal and pathological subject, in order to check the feasibility of this approach onto diabetic subjects.

Repeatability has been assessed by the mean, range and SD values of model segments and joint rotation angles, together with Vabs coefficient of Noonan 29, following the methodology proposed by Schwartz 32. The results showed the suitability of this method as they were found comparable with similar studies 19212921223031 and this gives strength to the present work. The repeatability analysis on the pathological subject shows results comparable to the normal one in terms of SD and Vabs in most of the rotation angles, which asses the suitability of this protocol to this type of patients.

Based on the results reported in Table 5 and [see Additional file 2], we can assess that the model has been tested for repeatability therefore anatomical landmark identification can be considered feasible.

The elementary movements were used in order to check the ability of the model to measure sub-segments rotations. The range, mean and SD values of the angles obtained by executing passive movements of the foot allowed us to test the suitability of the chosen reference systems and angles definition. We think this is in fact the only possible way to quantitatively assess the capability of the model of measuring correctly model segments rotations. Since the possibility of executing elementary movements of each model segment is still under study in our laboratory, model segments rotations were obtained by performing full foot elementary passive movements. Then the movement of each segment component was obtained by the model. The rotations relative to model segments are considered clinically acceptable 39.

A method for assessing foot subsegment three-dimensional kinematics have been obtained leading to results clinically consistent 39 and repeatable. The model has been tested for repeatability and shows results which agree with previous literature findings on kinematics data variability 1925293132.

Even though this study was applied to a limited number of patients, the proposed protocol appears to be clinically promising since it shows a good compliance by the patients. Indeed the neuropathic subject repeatability analysis shows results comparable with normal subjects. The marker set has been included in a full body protocol and has been implemented in routine clinical gait analysis of diabetic patients together with the simultaneous analysis through plantar pressure platforms and force plates 24. The results are considered sufficiently repeatable to guarantee the clinical application of the protocol.

Each of the authors has read and concurs with the content in the final manuscript.

The contributing authors guarantee that this manuscript has not been submitted, nor published elsewhere.

Each of the authors declare that don't have any financial and non-financial competing interests

Each of the authors has read and concurs with the content in the final manuscript.

ZS, GC, GG, AA, SC and CC participated in conceiving the study. ZS, GC, GG, AA and CC participated in its design and coordination and carried out the drafting of the manuscript. SC and GD helped to draft the manuscript. ZS carried out the experimental part of the study relatives to the motion analysis data collection and carried out and coordinated the data analysis. GD, AF and PD participated to the experimental part of the study relatives to the motion analysis data collection and performed some of the data analysis. GC and GG carried out the experimental part of the study relatives to the Neuropathy Diagnosis and participated to the motion analysis data collection.