(M0930-10-55) Protective Effects of Angiotensin Receptor Blockers on Knee Joint Cartilage Volume: A Retrospective Analysis of Osteoarthritis Initiative Study

Purpose: Osteoarthritis (OA) is a degenerative disease of the joints affecting hyaline articular cartilage of the knee, hip, fingers, and lower spine that occurs commonly in middle-aged and older adults. Knee being the most frequently affected site of all joints. OA is one of the leading factors responsible for morbidity and it can also lead to disability. Losartan- an angiotensin receptor blocker (ARB) in murine osteoarthritis model displaying the heterozygous chondroplasia gene (cho/+), a col11a1 mutation reduced cartilage loss in temporomandibular joint (TMJ) condylar and knee joint articular cartilage. The mechanism suggested is the inhibition of TGF-beta. Angiotensin receptor blocker are widely used drugs for cardiovascular  ailments and as organ, micro and macrovascular protective in various disorders including diabetes. Many osteoarthritis patients taking these drugs primarily to treat other ailments and disorders may be offering protective benefits on preventing cartilage loss. Thus, this retrospective analysis is aimed to explore the effects of angiotensin receptor blockers on cartilage volume in knee joints in patients with knee osteoarthritis using publicly available Osteoarthritis Initiative data (NIH) database.

Methods: Data for the study was obtained from the Osteoarthritis Initiative (OAI), a multi-center, prospective, longitudinal, observational, cohort study of knee osteoarthritis. The study participants comprised of persons who currently suffer from or are at elevated risk for developing knee osteoarthritis. The seven-year project recruited participants total of 4796 men and women ages 45-79 enrolled between February 2004 and May 2006. Images collected throughout the study include baseline and annual bilateral knee x-ray and bilateral knee MRI and other joint imaging. Two sub cohorts, an incident cohort and a progressive cohort were included in the OAI. Our study focused on the progression subcohort, which consisted of 1390 subjects with knee OA. OA is defined as having both frequent knee symptoms on most days for at least one month during the past year and radiographic tibiofemoral knee OA and radiographic knee OA is defined by definite tibiofemoral osteophytes. The incidence subcohort consisted of 3284 participants at elevated risk for knee OA. There were 122 subjects placed into non-exposed control group. Specific datasets for analysis included enrollees (participant cohort and demographic information), mif (Medication use), allclinical00 (Participant age), kmri_qcart_eckstein (knee MRI). Study observation included were for timeline 0, 12, 24, 36 and 48 months post enrollment. Data were then extracted for the subjects with or without being on angiotensin receptor blockers. In the data set normalized cartilage volume is calculated by dividing the cartilage volume by total area of subchondral bone. Mean and standard deviation for normalized medial tibia cartilage volume (mm) were obtained for both groups using SAS software.

Results: Our analysis of the progression sub cohort included 4122, 3409, 3219 828 and 1250 knee MRI observations for 0, 12, 24, 36 and 48 months respectively post enrollment for subjects without any ARB medication use and 281, 1950, 1873, 216, and 453 respectively for subjects with ARB use. The majority of participants were white or Caucasians. Subjects in ARB group were on one or more of the following ARB: Candesartan (n=33), Eprosartan (n=2), Irbesartan (n=69), Losartan (n=137) Olmesartan (n=52), Telmisartan (n=11), and Valsartan (n=165). Duration of ARB use was less than a month to more than 5 years. Mean normalized cartilage volume for without ARB and with ARB groups at baseline, 12 months and 24 months, 36 months and 48 months shown in figure 1. Mean normalized cartilage volume ranged 1.65-1.49 mm for both groups. Over the period of four years, there was a progressive decline in cartilage volume in both groups (figure 1). However, our analysis shows that there was lower loss of cartilage volume with patients on ARB over baseline at subsequent visits post enrollment. A visible trend was observed, however there were no significant differences noted over baseline.

Conclusion: This study provides association of angiotensin receptor blocker with preventing loss of cartilage volume in patients with knee osteoarthritis. Our study suggests that patients with osteoarthritis could benefit from the use of ARB to lower the rate of loss of cartilage volume. Further analysis is needed to ascertain the various risk factors such as age, gender, race, comorbidities etc, location of cartilages in knee joints (lateral, medial, central etc) and association of ARB use to reducing loss of cartilage.

References: M. Thomas, Z. Frank, A. Gross, D. Willmore, A. Arango, C. Higham, V. Nguyen, H. Lim, V. Kale, G. McMillan, R. E. Seegmiller, Losartan attenuates progression of osteoarthritis in the synovial temporomandibular and knee joints of a chondrodysplasia mouse model through inhibition of TGF-beta1 signaling pathway, Osteoarthritis and Cartilage, 2019, 27; 676-686.

Acknowledgements: Authors have no acknowledgement to disclose

Normalized cartilage volume in knee joints (Medial tibia)

Demographic characteristics of participants

Number of subject knee observations and cohort information with or without Angiotensin receptor blockers