Prognostic Factors in Zygapophyseal Osteoarthritis Infiltration: a Prospective Cohort Study
Prognostic Factors in Zygapophyseal Osteoarthritis Infiltration: a Prospective Cohort Study
Magnet Resonance Image findings of facet osteoarthritis and patient characteristics are
 prognostic factors for improvement or worsening of the clinical outcome after treatment with
 facet infiltration.
1. Introduction: Low back pain is one of the major health problems, studies show that it
 can affect 80-85% of people throughout life; consisting of the second major cause of
 work withdrawal. In the investigation by lumbar spine imaging methods, facet
 osteoarthritis (FO) is one of the most prevalent diagnoses, in the order of 59.6% for
 men and 66.7% for women. The process of osteoarthritis begins early in the spine, more
 than half of adults are under 30 years old, presenting degenerative changes in the
 facets, being more commonly affected the L4-L5 level. It is estimated that the pain of
 facet origin corresponds to 30% of cases of low back pain. The treatment of low back
 pain, which presents questionable results, has a strong economic impact on the health
 system and represents a growing concern for public and medical policy makers. The lack
 of diagnostic accuracy and the various types of treatment, without evidence of
 appropriate effectiveness, are considered the main causes of the increasing costs of the
 health system. As demonstrated by biomechanical, neuroanatomical and neurophysiological
 studies, there are free and encapsulated nerve endings in the lumbar facet joints as
 well as nerves containing substance P and peptide related to the calcitonin gene.
 Chemical or mechanical stimuli can cause pain. The pathophysiology of facet pain is not
 fully understood, but it is believed that facet osteoarthritis is due to repetitive
 mechanical stress, with subsequent inflammation and elongation of the joint capsule,
 generating pain.

 Several treatments are used in low back pain secondary to FO. The most used are
 non-hormonal anti-inflammatory drugs and physiotherapy, as a conservative measure.
 Interventional procedures such as facet intraarticular or periarticular infiltration of
 corticoid for neural blockade and denervation by radiofrequency are considered minimally
 invasive options, indicated for cases in which conservative treatment fails. Surgical
 treatment of arthrodesis is also part of the therapeutic options. The use of a systemic
 corticosteroid is within the available therapeutic arsenal but has undesirable side
 effects and its use is restricted in a short period of time. In order to increase drug
 concentration at the symptom site, without the undesirable side effects of the systemic
 corticosteroid, facet intraarticular infiltration (FI) has been used as a complementary
 treatment. The therapeutic value of FI is not consensus, with widely divergent results
 in the literature. Even so, it is one of the most used treatments, observing a growing
 demand of this procedure in the last decades. The selection of the appropriate patient,
 who would benefit from the treatment, is a determining factor in the outcome of the FI,
 since in thesis, only the subgroup of patients with inflammatory process in activity in
 the facet joint, would have a positive result with corticosteroid infiltration . The
 identification of this subgroup of patients is a challenge because the diagnosis of
 facet origin pain is often imprecise. With proper and accurate diagnosis, FI is expected
 to achieve better results. Magnetic resonance imaging (MRI) has the ability to identify
 the morphological characteristics of facet osteoarthritis, generating a classification
 in degrees mild, moderate or severe. It also allows to diagnose the presence or absence
 of an inflammatory process in the facet joint, which is usually manifested by indirect
 signs such as bone edema, periarticular soft tissue edema, joint effusion and synovitis.
 However, morphological characteristics and inflammatory markers of MR imaging have not
 been tested as prognostic factors of FI efficacy. Patients' characteristics such as
 gender, age, schooling, family income, smoking, body mass index, professional activity
 may have an effect on the expected results, but they have not been tested as prognostic
 factors of FI efficacy.

 1.1 Rationale: The relationship between MRI findings of facet osteoarthritis and the
 effect on FI of corticoid and anesthetic has not been studied. The relationship between
 the characteristics of age, sex, education, family income, smoking, body mass index,
 professional activity and the effect on FI of steroids and anesthetics has not been
 studied.

 Determining the prognostic factors may have an impact on the clinical routine of
 physicians and patients, guiding the treatment and selecting those with chances of
 better results with the FI.

 1.2 Hypotheses: MRI findings of facet osteoarthritis and patient characteristics are
 prognostic factors for improvement or worsening of the clinical outcome after treatment
 with FI.

 2. Purpose: To determine the prognostic factors of corticoid and anesthetic infiltration in
 the treatment of facet osteoarthritis in the lumbar spine. To determine the association
 between MRI imaging findings and pain, functional disability and patients' quality of
 life. To determine the association between age, sex, schooling, family income, smoking,
 body mass index, professional activity in pain, functional disability and quality of
 life of the patients.

 3. Method: This is a prospective cohort study that will include all patients with clinical
 suspicion of facet pain, who have undergone MRI and have been referred to the
 intervention center of the image department of a tertiary hospital, to perform FI with
 corticoid and anesthetic. On the day of the procedure patients will be invited to
 participate in the study. Before performing the facet infiltration patients will respond
 to informed consent form (ICF) and five questionnaires: 1. data collection form; 2. the
 visual analogue pain scale (VAS); 3. Roland-Morris questionnaire on functional
 disability; 4. Oswestry questionnaire on functional disability; 5. EuroQol questionnaire
 (EQ-5D) on quality of life. To measure the effect of the proposed treatment, all
 patients will be followed for one year, responding by telephone VAS, Roland-Morris,
 Oswestry and EQ-5D questionnaires at 1, 3, 6 and 12 months after the FI . The systemic
 use of corticosteroids, the performance of another infiltration or surgery and the
 amount of analgesics ingested per day will also be evaluated in the follow-up.
 Researchers will only apply the specific questionnaires of the project, having no
 influence on the indication, accomplishment and treatment of FI complications or on the
 clinical routine of the intervention center. To characterize the sample, the following
 variables will be collected: age (years), sex (male or female), schooling (years of
 study), smoking (number of cigarettes per day), family income, professional activity
 (type of occupation, number of hours sitting or standing, carrying weight or not) and
 oral analgesic use (number of tablets taken per day). The FI procedure will be guided by
 computed tomography. The radiation dose used will be the minimum possible to obtain
 images with sufficient quality to guide the location and progression of the needle,
 being within the limits established in the institutional protocols and already practiced
 in the department. After image confirmation of the correct intraarticular positioning of
 the needle, a solution containing triamcinolone 20mg / ml and hydrochloride of naropin
 in a ratio of 1: 1, in the volume of 1.5 to 2.0 ml, will be injected. After the
 procedure, the patient will be discharged and will be advised to do home rest for 24
 hours. The study design proposes to determine the correlation between the clinical
 outcome measured by the results of the VAS, Roland-Morris, Oswestry and EQ-5D
 questionnaires, and the variables identified by MRI and also the correlation between the
 clinical outcome and the variables: age, sex, educational level, smoking, family income,
 body mass index (BMI), professional activity and amount of analgesics ingested per day .
 To measure the effect of the proposed treatment, all patients will be followed for one
 year, responding by telephone VAS, Roland-Morris, Oswestry and EQ-5D questionnaires at
 1, 3, 6 and 12 months after the IF . The systemic use of corticosteroids, the
 performance of another infiltration or surgery and the amount of analgesics ingested per
 day will also be evaluated.

 3.1 Image exams and evaluator: All the lumbar spine MRI scans performed by the patients will
 be analyzed. Two radiologist will read MRI exams without knowledge of clinical, laboratory,
 or patient evaluation and questionnaire results. The variables degree of facet
 osteoarthritis, bone edema, peri-articular edema, synovitis, effusion, osteophytes,
 subchondral sclerosis, subchondral cysts, sliding, sagittal or horizontal orientation,
 identified by MRI, will be tabulated.

 3.2 Rating: MRI studies will be evaluated respecting patients' anonymity. Patients'
 characteristics, MRI imaging findings and VAS, Roland-Morris, Oswestry and EQ-5D
 questionnaires will be tabulated according to the following characteristics: age, sex,
 schooling, family income, smoking, weight , height, body mass index (BMI), occupational
 activity, analgesic ingestion, laterality, location, degree of facet arthritis, bone edema,
 peri-articular edema, synovitis, effusion, osteophytes, subchondral sclerosis, subchondral
 cysts, orientation sagittal or horizontal, facet sliding, VAS, Roland-Morris, EQ-5D and
 Oswestry.

 3.3 Sample size estimation: Taking into account the main variable of the study as the
 presence of inflammatory process in the facet joint, identified at MRI, with expected
 prevalence of 30% in the sample and as the main outcome the functional disability, as
 measured by the Roland-Morris questionnaire, when checking the sample size needed to detect a
 difference between the groups, with and without inflammatory process, before and after the FI
 procedure, it will require 117 patients in total, with a difference in the mean of the groups
 of 4.0 points. This calculation considered that the standard deviation of the difference of
 averages between the groups would be homogeneous and of 7.0 points, as observed in the
 literature. Considering the possibility of loss of follow-up in 20% of the cases, it is
 intended to include 147 patients in the study. Once the study has a six-month follow-up of 20
 patients, the calculation of the sample size needed to compare the groups with and without
 the inflammatory process will be recalculated based on the standard deviation observed in
 this study. The calculations were made considering 80% test power and a significance level of
 5%.

 3.4 Statistical analysis: Patient characteristics, MRI findings and pain (VAS), disability
 (Roland Morris and Oswestry), quality of life (EQ-5D) scores will be described by means of
 absolute frequencies and percentages in categorical variables, or through means, standard
 deviations or medians and quartiles, in addition to minimum and maximum values, in
 quantitative variables. The MRI characteristics analyzed by two observers will be evaluated
 for agreement by means of correlation coefficients appropriate to the observed distribution
 of number of cases, such as the Kappa coefficient.To evaluate MRI findings and patient
 characteristics (age, sex, smoking, family income, BMI, education, occupation and analgesic
 intake) in the evolution of pain (VAS), disability (Roland Morris and Oswestry) and of
 quality of life (EuroQol) during twelve months after infiltration, will be used mixed linear
 models or generalized linear models, in multiple approaches, being such models appropriate
 for measurements obtained from the same patient at different times. The results of the models
 will be presented by effect estimates (change in mean pain or in means of functional
 disability and quality of life) and 95% confidence intervals.

 We plan to carry out the analyzes with the aid of the statistical package R and considering
 significance level 5%.
Inclusion criteria

 The following are inclusion criteria for participants:

 -  Older than 18 years;

 -  Fluent or native Portuguese language speaker;

 -  Continuous or intermittent low back pain for at least three months;

 -  Low back pain with or without irradiation to the gluteal region indicating facet
 syndrome (pain is aggravated by spine extension or bending toward the affected side;
 pain is exacerbated by prolonged sitting or walking up steps, as well as retaining one
 position for a prolonged time);

 -  Failure of traditional treatment includes, but is not limited to, physical or drug
 therapy;

 -  Understand the purpose of the study;

 -  Voluntarily provide a free and informed consent form, by themselves or through their
 partners, and complete the questionnaires, before undergoing infiltration, over the
 telephone or online during the follow-up.

 Exclusion criteria

 The following are exclusion criteria for participants:

 -  Younger than 18 years old,

 -  Symptomatic lumbar spinal stenosis with claudication or radiculopathy;

 -  Evidence of radiculopathy;

 -  Active rheumatologic diseases;

 -  Congenital or acquired deformities of the lumbar spine;

 -  Fracture or sequel of lumbar spine fracture of traumatic, pathological or osteoporotic
 origin;

 -  Surgical manipulation of the lumbar spine;

 -  MRI scans of limited quality and incomplete sequences;

 -  Treated with systemic steroids less than one month before the IFI;

 -  Treated with IFI with steroids within the last six months;

 -  Diagnosed with uncontrolled diabetes mellitus;

 -  History of allergy to anesthetics or adverse reaction to steroids;

 -  Pregnant women or women who breastfed;

 -  Who could not be contacted over the phone during follow-up.