Patients using beta-blockers are less likely to undergo knee arthroplasty, reports Journal of Bone & Joint Surgery
September 7, 2023 – Among patients with knee pain, those who take a widely used class of blood pressure-lowering medications called beta-blockers appear to have a lower risk of total knee arthroplasty (TKA) for the treatment of advanced osteoarthritis (OA), suggests a study in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.
“Our results indicate that the use of β-blockers, especially nonselective blockers, was associated with a lower likelihood of TKA,” according to the case-control study by Iskandar Tamimi, MD, PhD, of Universitario de Malaga, Spain, and colleagues. Beta-blockers may slow the progression of OA by reducing inflammatory mediators involved in cartilage degeneration – which may provide clues to the development of new treatment approaches for OA.
Non-selective beta-blockers linked to 54% reduction in TKA risk
Using a Spanish hospital database, the researchers identified 300 patients who were evaluated for knee pain between 2010 and 2019 and who underwent TKA between 2018 and 2019. These case patients were matched for age, sex, calendar year, and grade of arthritis to 300 controls who were evaluated for knee pain but did not undergo TKA.
Beta-blocker treatment was evaluated for possible effects on the risk of undergoing TKA. The analysis included the duration of beta-blocker treatment and, as a measure of treatment adherence, the percentage of days with a filled prescription. A validated artificial intelligence tool was used to minimize bias in adjusting for other factors potentially related to TKA risk.
In the adjusted analysis, patients with any use of beta-blockers were about half as likely to undergo TKA. The association was specific to non-selective beta-blockers, which target both beta-1 and beta-2 adrenergic receptors. For patients with knee pain taking these medications, the risk of undergoing TKA was reduced by 54%. In contrast, patients taking selective beta-blockers – which target beta-1 receptors located mainly in the heart – had no significant reduction in TKA risk.
Findings may point to new treatments to ‘delay the progression of OA’
The protective effect was even stronger with prolonged use of beta-blockers: patients taking beta-blockers for five years or longer had a 64% reduction in TKA risk. The association was also stronger for patients with greater adherence, with a filled prescription on at least 75% of days.
Previous studies have suggested that beta-blockers downregulate various inflammatory mediators involved in OA. Several of these mediators are regulated by the adrenergic pathways responsible for the blood pressure-lowering effects of beta-blockers.
“Thus, downregulation of the adrenergic signal could potentially decrease cartilage degradation and delay the progression of OA,” the researchers write. They note that their study cannot draw any conclusions regarding the “true causal link” between beta-blocker treatment and the risk of undergoing TKA.
“We believe that the role of β-blockers in the management of OA could go beyond an analgesic treatment and that these drugs potentially could interfere with the degenerative processes in the cartilage,” Dr. Tamimi and coauthors conclude. While further research is needed, the study “provides a hypothesis for the development of future therapeutic lines targeting the adrenergic system in the treatment of OA.”
Read Paper [The Use of β-Blockers and the Risk of Undergoing a Knee Arthroplasty]
I wonder if there is a possibility that the beta 2 adrenergic receptor blockage of the non-specific blockers might actually decrease skeletal muscle power, and have a protective effect on cartilage in that way?
It’s a curious finding of association with the use of β-blockers (particularly non-selective ones) with outcome of TKR, keeping in mind that in a study with multiple variables of more than 20 being analysed it is not impossible that this finding can occur by chance. Although the author states ” the purpose of the present study was to analyze the relationship between the use of β-blockers in patients with knee pain and the risk of undergoing a TKA as a result of advanced knee OA”, in absence of previously published protocol (the article did not refer to one, nor a simple search of the authors’ ORCID background reveal any), it is not certain that the true intent of this study was originally to focus on β-blockers. Nevertheless I do find their result intriguing.
However what is more confusing is the authors’ conclusions. They stated:
“Our results indicate that the use of β-blockers, especially nonselective blockers, was associated with a lower likelihood of TKA. Patients treated for prolonged periods had a lower likelihood of TKA. This study provides insight to a possible relationship between the activity of the autonomic nervous system and the progression of OA. In addition, it provides a hypothesis for the development of future therapeutic lines targeting the adrenergic system in the treatment of OA.”
This is quite surprising as a significant proportion of their discussion also focussed on possible pain modulation by β-blockers which presents an important alternative (or concurrent) hypothesis in why β-blockers users are less likely to have TKR. Many experienced clinicians are well aware of that high grade radiological appearance of knee osteoarthritis does not always translate to severity of knee pain and other symptoms, hence there is a nuance in shared decision-making when proposing treatment approach for patients with apparently radiologically proved advanced osteoarthritis. This philosophy is reflected in the protocol for TKR in the authors’ own institution, Hospital Regional Universitario de Málaga. More importantly at least one third of those who have undergone TKR has Kellgren-Lawrence grade 2 or less, hence the decision to operate could not have depended just on the “advanced OA involving at least 1 of the 3 compartments of the knee” criteria.
Unfortunately, despite the study being drawn from the hospital database of patients who attended the orthopaedic outpatient clinic with a history of new-onset knee pain between 2010 and 2019, with outcome of any primary TKA between 2018 and 2019 in these patients, the authors did not make any apparent determination if these patients demonstrated variation in progression of knee osteoarthritis according to β-blocker usage, considering the time gap between presentation at the clinic can be as wide as 9 years, with average follow-up period in this nested study being about 2 years.
Perhaps this is for another time; if not, a gold opportunity missed.