Clinical diagnosis of osteoarthritis

Significant progress in understanding the pathophysiology and evolution of osteoarthritis led not only to improved diagnosis of the disease, but also to a reassessment of the methodology and metrology of conducting clinical studies in osteoarthrosis. Clinical diagnosis of osteoarthritis is difficult. This is due to a number of factors:

• often asymptomatic disease
• dissociation between the radiological picture and clinical manifestation,
• frequent inconsistency between arthroscopy and X-ray of the affected joints,
• the lack of reliable biological markers of cartilage metabolism, reflecting the progression of osteoarthritis and having prognostic value,
• individual for each localization of osteoarthritis (hands, knee, hip joints, etc.) evaluation criteria, but together they are not suitable for generalized forms of osteoarthritis.

In connection with the appearance on the pharmaceutical market of new drugs for the treatment of osteoarthritis and a large number of publications with the results of controlled studies, it has become necessary to develop unified criteria of effectiveness. The list of indicators that could be included in the protocol of a clinical trial of osteoarthrosis is quite large. These indicators can be divided into: subjective (indicators of pain, functional capacity, quality of life) and objective - characterizing the progression of the disease (according to x-ray, MRI, arthroscopy, ultrasound, radioisotope scanning; biological markers).

[1], [2], [3], [4]

Pain

Most often, a visual scale of pain (YOUR Huskisson) and a Likert scale are used to assess pain syndrome in patients with osteoarthrosis. The results of numerous studies have demonstrated their highly informative. The first one is a vertical or horizontal straight line with a length of 10 cm (0 cm - no pain, 10 cm - the most pronounced pain), the second is the same straight line on which the “pain scores” are from 0 (no pain) to 5 (the most pronounced pain ). Variants of the “classic” analogue scales — the chromatic analogue scale and others — are rarely used in clinical studies of osteoarthritis. Since pain is a subjective symptom, the patient should note its severity on the appropriate scale.

[5], [6], [7], [8]

Morning stiffness

Morning stiffness in patients with osteoarthritis is a variable symptom; compared with patients with rheumatoid arthritis, its duration is much shorter (no more than 30 minutes). Therefore, it is less important in assessing the status of a patient with osteoarthritis than, for example, pain in the joints. N. Bellamy and WW Buchanan (1986) suggested that patients with osteoarthritis themselves evaluate the importance of this symptom. Most patients found morning stiffness a moderately important symptom. Given the short duration of this symptom, it is advisable to assess its severity, rather than duration (unlike rheumatoid arthritis). To facilitate evaluation, analog scales are adapted for the indicator of morning stiffness.

[9], [10], [11]

Travel time 50 feet

This indicator is applicable only in the study of patients with osteoarthritis of the joints of the lower extremities. The results of a study conducted by N. Bellamy and WW. Buchanan (1984) showed that even in patients with gonarthrosis and coxarthrosis is poorly informative, so using the 50-foot transit time indicator in clinical studies in patients with osteoarthritis is doubtful.

Time to climb stairs

Similar to the previous indicator, the time for climbing stairs is applicable only if the joints of the lower limbs are affected. Standards are not defined for it (for example, the required number of steps). Furthermore, a number of related diseases ( cardiovascular diseases, diseases of the nervous system ) can significantly affect the performance of the test. Thus, the use of the indicator of the time of ascent of the stairs in osteoarthritis is also impractical.

Determination of range of motion

The determination of the range of motion in patients with osteoarthritis is applicable only to the knee joint. A limited range of movements in the knee joint can reflect not only changes in the articular cartilage, but also in the articular capsule, periarticular muscles, ligaments. When the limb is bent at the knee, the relative position of the axes of the femoral and tibial bones is changed so that the standard mechanical goniometer cannot measure the angle correctly. However, a properly trained specialist can correctly measure the angles of flexion and extension in the knee joint, in which case this test can be included in the study protocol. It should be noted that a statistically significant difference in the amount of movement in the knee joint between patients receiving active treatment (NSAIDs) and placebo was found in clinical studies.

[12], [13], [14], [15], [16]

Ankle spacing

The distance between the ankles at the maximum dilution of the lower limbs. This test, which characterizes the volume of reduction in the hip joint, can be quite informative, if performed by a skilled specialist. Its informativeness has been demonstrated in studies of the effectiveness of NSAIDs in patients with coxarthrosis. However, like other indicators of the geometry of the joints, this test is not recommended for use in clinical studies.

[17], [18], [19]

The distance between the medial femoral condyles

The distance between the medial femoral condyles at the maximum dilution of the lower extremities - a multidimensional test characterizing the volumes of adduction and external rotation in the hip joints and the amount of flexion in the knee - can be informative only if performed by a trained specialist. Similarly to the previous informational content of this indicator was demonstrated in a clinical study of the use of NSAIDs in osteoarthritis. The need to include this test in the study protocol is questionable.

Doyle Index

The Doyle Index is an adapted Richie Index, designed specifically for rheumatoid arthritis and osteoarthritis. The test method includes an assessment of the sensitivity of the joints during palpation and movements in them, as well as an assessment of joint swelling. For unknown reasons, he did not arouse the interest of rheumatologists, no one defined his information content. It is possible that after additional research, the Doyle index will be recommended for inclusion in the protocol of clinical studies of patients with generalized osteoarthritis.

[20], [21], [22], [23], [24],

Evaluation of joint swelling

Evaluation of joint swelling is controversial, since in patients with osteoarthritis it may be due not only to the swelling of soft tissues, but also to the growth of bone tissue. In the first case, against the background of treatment, we can expect the dynamics of the relevant indicators, in the second - no. Despite the fact that the measurement of the circumference of the joints in centimeters was included in the protocol of several studies, the information content of this test is limited and depends on the degree of preparedness of the researcher. The measurement of the circumference applies only to the knee and wrist joints. In the first case, you can use a standard centimeter tape, in the second - special plastic or wooden rings of different sizes. Even in clinical studies in which the experience of using this test is much greater, it is rarely included in the study protocol.

[25], [26], [27], [28], [29], [30], [31]

Assessment of carpal strength

The assessment of carpal strength using a pneumatic dynamometer is rarely included in the study protocols for osteoarthritis, probably because these studies rarely focus on osteoarthritis of the hands. This test, of course, must perform a specially trained researcher. With the pinching of the dynamometer I and II with fingers, it is possible to separately evaluate the first carpal-metacarpal joint of the patient’s hand with osteoarthritis. The complexity of interpreting the dynamics of the carpal force index reduces the value of the test for clinical studies.

[32], [33], [34]

Analgesic intake

When evaluating the effectiveness of symptomatic drugs used in the treatment of osteoarthritis, the main criterion is pain in the joints. In such cases, for an additional assessment of the dynamics of pain, an indicator of analgesics is used. Paracetamol is usually used for this. Along with the drug under study, the patient is recommended to take paracetamol with the obligatory filling of a specially designed diary if necessary. For an additional assessment of the effect on pain syndrome of drugs that are not in the symptomatic group (for example, chondroprotectors), you can use NSAIDs instead of paracetamol and then recalculate the dose taken to the equivalent of diclofenac. Given the higher incidence of side effects in the appointment of NSAIDs, preference should still be given to paracetamol. To objectify the treatment of painkillers special containers are developed with a microchip placed in the lid, which records the number of openings of the container.

Doses of NSAIDs equivalent to 150 mg of diclofenac (Recommendations of the French Ministry of Health for conducting clinical trials of osteoarthritis

NPVP	The dose equivalent to 150 mg of diclofenac, mg
Naproxen	1100
Ibuprofen	2400
Indometacin	100
Flurbiprofen	300
Ketoprofen	300
Pyroxycam	20

[35], [36]

Overall rating

This method can be estimated:

• treatment effectiveness
• treatment tolerance,
• functional ability of the patient,
• severity of pain.

The first three points are independently evaluated by the doctor and the patient, the last - only by the patient. Usually the overall score is carried out on a point system.

[37], [38]

Health assessment

Methods for assessing the health of patients with Osteoarthritis can be divided into specific and generic. Such a division is somewhat artificial, but it allows us to differentiate the methods used for all joints at the same time (specific) and for individual joint groups (generic).

[39], [40], [41], [42]

Index WOMAC (Western Ontario and McMaster Universities osteoarthritis Index)

The WOMAC test is a questionnaire for self-completion of patients, consists of 24 questions characterizing the severity of pain (5 questions), stiffness (2 questions) and functional ability (17 questions) of patients with gonarthrosis and coxarthrosis. It takes 5-7 minutes to complete the WOMAC questionnaire. The WOMAC Index is a highly informative indicator that can be used to assess the effectiveness of drug and non-drug (surgical, physiotherapeutic) treatment.

[43], [44], [45], [46], [47]

Algofunkional indexes (API) of Leken

M. Lequesne has developed two APIs - for osteoarthritis of the knee and hip joints. Lecken's tests also represent questionnaires for self-completion of patients, the questions are divided into three groups - pain or discomfort, maximum walking distance and daily activity. The question concerning the sexual sphere of the patient, which was included by the author in the questionnaire for coxarthrosis, is not necessary for the study of the effectiveness of antirheumatic drugs. Leken indices were recommended by EULAR as a criterion of effectiveness in clinical studies in patients with osteoarthritis (WHO, 1985), and, along with the WOMAC index, to evaluate the effectiveness of so-called slow-acting drugs (SADOA). Statistically informative and reliable indexes WOMAC and Leken are the same.

Algofuntional Dreiser Index

The algofunking Dryzer index developed specifically for clinical studies in osteoarthritis of the joints of the hands, is a ten-point questionnaire. Nine out of ten questions relate to the function of the joints of the hands, and the tenth (how willingly the patient responds to the handshake) reflects the severity of the pain syndrome. The Dreiser index is a relatively new and little-studied test, therefore, before ascertaining the degree of information content and reliability, it is better not to include it in the study protocol.

[48], [49], [50], [51], [52]

Health Assessment Questionnaire

The Health Assessment Questionnaire (HAQ) was developed at Stanford University by JF Fries et al. (1980), and therefore also has a second name, the Stanford Questionnaire. The questionnaire is easy to use and can be completed by the patient within 5-8 min without the intervention of a physician. The questions in the questionnaire are divided into 2 categories: self-care (get dressed, get out of bed, personal hygiene, etc.) and movement. The questionnaire is informative and reliable, it is recommended to use it to assess the health of a patient with generalized osteoarthritis.

[53], [54], [55], [56], [57]

AIMS

AIMS (Arthritis Impact Measurement Scale) was developed by RF Meenan and co-authors (1980). The 46 questions of the AIMS questionnaire are divided into 9 categories - mobility, physical activity, agility, social role, social activity, daily life, pain, depression, anxiety. G. Griffiths and co-authors conducted a comparative study of the WOMAC, HAQ and AIMS questionnaires and found some advantage first. The authors recommend using the WOMAC questionnaire in OA studies of the knee and / or hip joints, and the HAQ and AIMS questionnaires in studies of generalized osteoarthritis.

[58], [59], [60], [61], [62]

FSI

FSI (Functional Status Index) developed by A.M. Jette, OL Deniston (1978) as part of the Pilot Geriatric Arthritis Project. There are two versions of FSI: “classic”, consisting of 45 questions, classified sodium categories (addiction, pain, daily activity), which takes 60-90 minutes to complete, and a shortened (revised) one, consisting of 18 questions, grouped into 5 groups (general mobility, hand mobility, self-care, housework, interpersonal contacts), which takes 20-30 minutes to fill. A special feature of FSI is the mandatory participation of the interviewer (doctor, researcher) when filling out the questionnaire. FSI can be used in clinical trials in patients with generalized osteoarthrosis, although HAQ and AIMS should still be preferred.

[63]

Methods for assessing the quality of life

To date, several methods for assessing the quality of life have been developed. In clinical studies in patients with osteoarthritis, four of them can be used - Short Form-36 (SF-36) Health Status Questionnaire, EuroQol, Health Utilities Index and Nottingham Health Profile.

Short Form-36 (SF-36) Health Status Questionnaire consists of 36 questions for the patient to self-fill within 5 minutes. The SF-36 and the EuroQol form below are designed so that they can be filled in by the interviewer by phone or sent to patients by mail.

EuroQol (European Quality of Life Questionnaire) consists of two parts - a questionnaire of 5 questions directly and YOUR, on which the patient assesses his or her health.

The Health Utilities Index was developed specifically for patients with malignant tumors. The survey questions cover 8 signs: sight, hearing, speech, mobility, agility, cognitive ability, pain and discomfort, emotions. This questionnaire is very rarely used to assess the quality of life of rheumatic patients. Typically, preference is given to SF-36, less often - EuroQol.

The Nottingham Health Profile application includes 38 items divided into 6 sections: mobility, pain, sleep, social isolation, emotional reactions, activity level. The patient can also fill in this form independently. Like the previous profile, Nottingham Health Profile is extremely rarely used in rheumatology.

[64], [65], [66], [67],

Visualization methods

Chondroprotective properties, which are defined as "... The ability to slow down, stop or reverse the degenerative process in hyaline cartilage in patients with osteoarthrosis, have not been proven for any medicinal substance by now." This is largely due to the fact that the question of how to identify the phenomenon of chondroprotection and the possibilities in this regard, radiography or alternative methods (arthroscopy, MRI) has not yet been widely discussed.

Radiography

In recent years, a large number of publications have appeared on radiography of joints affected by osteoarthritis. Improved shooting techniques, a lot of quantitative (measuring the width of the articular gap) and semi-quantitative (evaluation in points, degrees) methods for evaluating radiographs in patients with osteoarthrosis. For major controlled studies radiography - the preferred imaging technique that can indirectly characterize the dynamics of morphological changes in joint tissues affected by osteoarthritis.

[68], [69], [70],

MRT

Using MRI in controlled studies, high cost and low availability is limited in osteoarthritis. Moreover, there is evidence of only partial concordance of damage to the articular cartilage found on MRI and arthroscopy. L. Pilch et al. (1994) discovered errors in the computer software used for volumetric studies of articular cartilage in osteoarthritis. Thus, it is necessary to further explore the possibilities of MRI in conducting clinical studies of patients with osteoarthritis.

[71], [72]

Scintigraphy

P. Dieppe et al. (1993) confirmed the ability to scintigraphy in predicting joint space in osteoarthritis. However, its role in assessing the dynamics of morphological changes in the tissues of the affected joints during clinical trials remains doubtful.

[73], [74], [75], [76]

Ultrasound

SL Myers et al. (1995) demonstrated in vitro that high-frequency ultrasound provides an accurate measurement of the thickness of the human articular cartilage, and also reproduces the exact image of its surface Besides Ultrasound is a fairly affordable method that is not associated with radiation exposure. However, the ability to determine the chondroprotective properties of medicinal substances using ultrasound has not been proven. Further study of the possibilities of ultrasound in this direction is required.

Arthroscopy

Arthroscopy provides the most reliable information about the state of articular cartilage and tissues of the joint cavity. A large number of chondroscopy evaluation systems have been developed. Despite this, the highly invasive method severely limits its use in clinical studies.
 

[77], [78], [79], [80], [81], [82]