The results of the study established that the major risk factors leading to KR are symptoms, disease severity and higher BMI and there was no association between exposure of oral OA therapies and the occurrence of KR.  

Osteoarthritis (OA) is one of the critical arthritis condition associated with chronic pain and disability. The treatment modality for OA includes many different pharmacological classes of agents. These pharmacological class of agents are oral and often prescribed for chronic administration for an extended period. In recent years, the safety of some of these drug treatments related to potential systemic effects such as cardiovascular risks, for instance, with non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs has been a significant concern. The increased use of narcotics by patients in OA also produces some detrimental effects leading to morbidity and mortality. 

Concerns about the effects of these drug treatments on the emergence of structural changes in OA, particularly in weight-bearing joints including the hip and knee has also been raised. The influence of such oral treatments (especially NSAIDs) on the progression and outcome of OA disease, either positive or negative, remains at this time an open question that needs to be further explored. 

The discovery of various studies concerning the effects of different therapeutic classes of drugs used as a treatment of OA and their potential impact on disease progression is a challenging task. However, the use of observational cohorts contributes to a real-life scenario. The Osteoarthritis Initiative (OAI) cohort presents various advantages owing to its size, duration, and abundant amount of comprehensive clinical and demographic information available on the study participants, including drug treatment. Assessment of structural changes by imaging using knee x-rays and magnetic resonance imaging (MRI) was also done. Magnetic resonance imaging (MRI) has proven to be reliable, sensitive, and worthwhile for studying disease outcomes. Joint replacement is considered as a clinically appropriate disease outcome in knee OA, related to both significant and structural damage. Another fundamental reason to choose a nested case-control design was robustness of the approach as well as measurement of the exposure to oral OA therapies in different time windows before the KR. 

Rationale behind research

The discovery of studies related to the effects of various treatments of OA and their impact on disease progression remains a difficult task. The present study was conducted to scrutinise the potential benefits of observational cohort studies in determining the potential effect of various OA treatment on disease progression and severity with an assessment of risk factors on the appearance of knee replacement (KR)

Objective

The present case-control study was aimed to determine the relatedness between exposure to commonly used oral OA therapies and relevant confounding risk factors related to the occurrence of knee replacement (KR), using the Osteoarthritis Initiative (OAI) database.  

Study outcomes:

• Baseline: The clinical and demographic variables such as age, gender, income level, WOMAC pain scores, KL grades, covariates, and arthritis drug treatment taken by the patients including acetaminophen, NSAIDs, COX-2 inhibitors, narcotics, and glucosamine/chondroitin sulfate were studied at baseline 
• Imaging characteristics studied were meniscal extrusion, change in cartilage volume in medial and lateral compartments of knee and quantitative BML.
• Other outcomes were exposure to oral OA therapies (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, narcotics, and glucosamine/chondroitin sulfate) within the 3 years prior to the date of the KR and assessment of association between KR and exposure to oral OA therapies and other potential confounding risk factors

Time Points: 2-5 years 

Outcomes

Baseline:

Study outcomes:

• There occurs a similarity in exposure to narcotics and glucosamine/chondroitin sulfate between cases and controls
• There was no significant correlation found between the occurrence of KR and exposure to any of the oral OA therapies within the three years before KR
• A significantly higher occurrence of KR was reported in Caucasian subjects (OR 1.84; 95% CI, 1.13–2. 99; p = 0.015) and subjects with BMI ≥ 27 kg/m2 (OR 1.65; 95% CI, 1.06–2.58; p = 0.027)

The present study demonstrated that exposure to some of the commonly used oral OA therapies, i.e. NSAIDs, COX-2 inhibitors, acetaminophen, narcotics, or glucosamine/chondroitin sulfate, in a period of 2– 5 years, was not correlated with the occurrence of KR when compared to no exposure to such medications. Many other risk factors including race, level of symptoms, and BMI were identified as being linked to KR.  The findings also revealed the neutral effect of oral medications on knee replacement controlling the most important confounding factors that promote such occurrences: clinical demographics, symptom severity, socioeconomic status, radiographic grading, and structural changes assessed by quantitative MRI. The clinical and sociodemographic data of our study population exhibits similarity with previous studies exploring the role of disease treatment on KR, but it does not explain the discrepancy in the effect of such NSAIDs. The study also established the use of KR as a sole marker and a logical outcome of disease progression. Indeed, MRI parameters evaluated in knee OA, such as the medial compartment cartilage volume/thickness, can also consistently predict outcomes such as KR. The cartilage volume at index (KR) time was also similar in both groups indicating a balance between the factors leading to the progression of cartilage volume loss up to KR in both the groups.

The present study exhibits several strengths such as inclusion of the large OAI database, including assessment of KR, based on patient and physician preferences in a context of a real-world scenario,  stratification of risk of KR by degree of exposure to oral OA medication v/s no exposure, great reliability  about the knee OA diagnosis and its KR indication dependent on detailed information on demographics, imaging, symptoms, and drug use for both patients and their matched controls,  minimizing the possibility of bias, and the excellent matching yielded from our control selection strategy.