Is there evidence that cholesterol medication is helping or hurting your joints?

Ross Hauser, MD., Danielle Matias, PA-C., Marion Hauser, MS, RD

High cholesterol, and its treatment with statins, have been a hallmark of cardiovascular disease management for decades. Many people worry about their cholesterol because they feel they have to, based on drug companies and the media bombarding us with the impression there is a one to one linkage between elevated blood fats and arteriosclerosis. The benefits, side effects, and even the worthiness of taking statins have been under constant attack in recent years. One of the side-effects reports, statins’ negative influence on soft tissue, namely tendons and ligaments, will be the focus of this article.

To be clear, many people benefit from taking statins. The focus of this article is to discuss the research that suggests statins may help joint pain or that statins may make joint pain worse. Further that statins may in fact cause muscle atrophy and deterioration.

Soon after taking these new cholesterol medications, I felt a sharp and sudden pain in my knee

A patient comes in on a recommendation from a friend.

“I am here because I have very bad knee pain . . . here is my story:

I went to the doctor for my check-up. My blood work revealed slightly elevated cholesterol and I was advised that I need to take and was given prescriptions for medications that would lower my cholesterol. I also told my doctor that my knee was hurting, could I get something for it? My doctor asked, when and how the knee pain started? I said I aggravated it with a new exercise program, one I would hope that would lower my weight and cholesterol. My doctor said, “go easy on my knee.”

Soon after taking these new cholesterol medications, I felt a sharp and sudden pain in my knee as my wife and I were walking to our car. My wife drove us home and she got me to the chair and we elevated my leg and got plenty of ice on it.

We made an appointment at the doctors. Here I was given the reason why my knee hurt. 

• It must be the exercise program. I should go slower or completely rest.

After a week of not exercising at all, my knee pain, now the pain was in both knees, became so much worse, I could not sleep. My wife began looking up things on the internet. She showed me some articles that said it was the statins, the cholesterol medication causing the knee pain. In fact, she showed me, it is a well-known side-effect.

We made an appointment at the doctor’s where I was told to reduce the cholesterol medication and slowly work my way back up to tolerating it if, in fact, that was causing the knee pain. My doctor was skeptical. 

Even after lowering the cholesterol medication dosage I still had the same pain. My doctor told me to stop taking the statins. After a few days, maybe a week or two, my knee pain reduced significantly but they were still painful. I returned to the doctor and told him that I would try to manage my cholesterol without medications and we will see how I do. I am here because I cannot exercise with my knees like this.

Statins can create pain? Reduce pain? – Let’s start with the research

In August 2019, an international team of university researchers and various national councils published these findings in the journal Arthritis Care and Research (1).

Key learning points:

• The research surrounding the possible relationship between statin use and outcomes in knee osteoarthritis is limited.
• This study examined 1,127 adults for 4 years who took statins.
• What the researchers were looking for was how did statin use influence:
  • Radiographic osteoarthritis, (how did the knee look in MRI and scans over the 4 year period. Did the MRI/scans look worse?)
  • Symptomatic knee osteoarthritis (did the person in the study have new knee pain symptoms and was this matched by eroding conditions in the knee on MRI and scans?)
  • Overall, did the person’s knee pain get worse?

Conclusion: Statins are good and are not good pain medications

• No matter what statin was used: Statin use was not associated with a lower risk of worsening pain. In other words, statins were not good pain medications.
• Atorvastatin (Lipitor) use was associated with a reduced risk of developing pain, whilst rosuvastatin (Crestor) leads to a higher risk of developing pain.

From the researchers: “The effect of statins use on knee osteoarthritis outcomes remains unclear, although in our study those using statins for over five years and those using atorvastatin reported a significantly lower risk of developing knee pain.”

Confusing right?

• First, the Atorvastatin (Lipitor) user was associated with a reduced risk of developing pain AS COMPARED to (Crestor) which lead to a higher risk of developing pain. So the Atorvastatin produced less knee pain risk, but still a risk.
• Either way, if you already have knee pain, cholesterol-lowering medicine will not help make it less painful or from it getting worse.

So again, all these research universities and national resources and a long-term study of over 1000 patients came to this conclusion: “The effect of statins use on knee osteoarthritis outcomes remains unclear.”

Researchers suggest statins do not make knee osteoarthritis worse

Now let’s look at two 2022 papers that cited this 2019 research. First, doctors at the University of British Columbia and Boston University School of Medicine publishing in October 2022 in the journal BioMed Central musculoskeletal disorders (2) evaluated the effect of statin use on osteoarthritis incidence and progression. In this study, a group of knee pain patients from age 40-79 were evaluated using an MRI. The patients were using statins. Primarily, the doctors were looking for the breakdown of cartilage over the 7 year study period and to further assess the progression of bone spurs, bone marrow lesions, and chronic swelling.

• Of 122 participants  who completed the 7-year follow-up. Statin use was not significantly associated with progression of cartilage damage, bone spurs, bone marrow lesions, or knee swelling.
• In this study, the researchers suggest that statins do not make knee osteoarthritis worse.

Researchers suggest statins make knee osteoarthritis worse, especially at higher doses

A November 2022 paper in the Frontiers in Pharmacology (3) also citing the 2019 research, took a slightly different path in their findings. Here the researchers suggested that “statin use might be associated with increased osteoarthritis development, especially at higher doses. The present study highlights the importance of recognizing potential osteoarthritis risk in the population with long-term and/or high-dose statin use, especially in older populations.”

The story of cholesterol-lowering medications and joint pain surrounds the impact of these medications on inflammation. Are statins anti-inflammatory or do they create more inflammation? Eleven years of current research.

There is no general consensus that statins help or statins make things worse. We highlighted the studies above because these findings are built on other research that took counter viewpoints. Let’s explore the debate further with research that takes us from 2012 to 2023.

In 2012, a study from the Netherlands and a team of Dutch university researchers published in the Annals of the Rheumatic Diseases (4) found that Statin use is associated with more than a 50% reduction in the overall progression of osteoarthritis of the knee.

Yet, in 2013 Virginia Commonwealth University researchers published in the same journal the Annals of the Rheumatic Diseases these findings:(5)

• Statin use was not associated with improvements in knee pain, function, or structural progression trajectories.
• The only significant finding indicated that increased duration of statin use was associated with worsening knee pain and osteoarthritis. 

The doctors from the Netherlands responded in print a few months later in a proper scientific debate. In this response in the Annals of the Rheumatic Diseases, (6) it was suggested that parts of their study should be re-evaluated to find the benefits of statins. They point out

• “Considering the theoretical effects of statins on osteoarthritis (lowering of serum lipid levels lowering local and systemic inflammation, and prevention of atherosclerosis), it is more plausible that statins could be useful in the early stages of osteoarthritis or even before the initiation of the disease process.”

Statins being effective at early stages or preventative in post-trauma injuries was suggested in a paper from Ulm University in Germany published in the Frontiers in Bioengineering and Biotechnology (7) suggested statins may be an effective initial treatment to prevent post-trauma osteoarthritis. Here the results and message of the benefits of statins in acute injury seemed mixed. “While long-term administration of statins for 4 weeks impaired chondrogenic redifferentiation (cartilage growth), addition of simvastatin at low concentrations for 1 week exhibited a slightly promoting effect. In conclusion, our data imply that simvastatin and fluvastatin are suitable in terms of initial harm reduction after cartilage trauma.”

More debate on whether statins help or do not help joint pain, or in fact, make joint pain worse

In September 2022, a team of multinational researchers writing in the journal Current Rheumatology Reviews (8) gave this firm recommendation. Statins do not help. Here is what they said: Statins are used to lower serum cholesterol. Recently there has been interest in statin’s ability to regrow cartilage.  In reviewing previously published studies, the authors found “the effect of statins on human osteoarthritis is inconclusive: some showing improvement of osteoarthritis symptoms, and others depict signs of aggravation and radiological progression. No randomized controlled trial (RCT) has tested the efficacy of intra-articular statins in clinical knee osteoarthritis, and it seems feasible to avoid oral statin-associated severe adverse effects.” Finally, “There are no arguments to recommend oral statins in clinical osteoarthritis of the knee.”

A November 2022 paper in the journal Frontiers in Medicine (9) examined the effects of cholesterol levels and cholesterol-lowering medications on osteoarthritis risk. The researchers looked at low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels impact on knee and hip osteoarthritis. Their results suggested that low-density lipoprotein cholesterol (LDL-C) has independent protective effects on both knee and hip osteoarthritis. Decreasing LDL-C with statins may increase the risk of knee osteoarthritis.

If I control my cholesterol with diet and exercise, instead of medications, my knee pain can be helped without the medication’s side effects.

Here medical and university researchers published their findings in the influential Scientific Reports (10) from the Nature Publish group in London.

• In the present study of nearly 14,000 participants, the research team identified a positive association between hyperlipidemia (high cholesterol) and elevated risks of knee pain and clinical knee osteoarthritis in middle-aged or older adults.
• There is a relationship between triglycerides and knee osteoarthritis.
• Study results indicate that the influence of lipid-lowering drugs on knee pain and clinical knee osteoarthritis is limited.
• These findings have notable implications for public health because the relatively high prevalence of knee osteoarthritis seriously affects the quality of life for older adults, and hyperlipidemia may be prevented through diet and physical exercise.

The researchers then sought to clarify the contradicting research presented in the two studies above.

• The first study above from the Netherlands demonstrated that lipid-lowering drugs were associated with slower knee osteoarthritis progression.
• The second study from Virginia did not find the same results
• In this study from China, the researchers:
  • did not observe an increased risk of knee pain or clinical knee osteoarthritis among the group of participants without high cholesterol but taking lipid-lowering drugs for the prevention of other diseases.
  • However, among participants with high cholesterol, risks for knee pain and clinical knee osteoarthritis were higher among those taking lipid-lowering drugs than among those not taking such drugs.
  • Possible explanations for this finding may be that the participants with hyperlipidemia and the use of lipid-lowering drugs had higher serum lipids before pharmacotherapy and a longer course of hyperlipidemia. Our results suggest that hyperlipidemia may be an independent risk factor for knee osteoarthritis and that the effect of lipid-lowering drugs on this association is limited.

They concluded that their results indicate that hyperlipidemia may be an independent risk factor for knee pain and clinical knee osteoarthritis among middle-aged or older adults. These findings have substantial implications for the prevention of knee osteoarthritis through the reduction of blood lipid levels.

Does statin use in healthy knee individuals lead to knee replacement?

In an October 2018 study led by the VA North Texas Health Care System, (11) doctors questioned the use of statin prescriptions as preventative medicine in healthy individuals because:

• Statins are among the most commonly prescribed medications and their use for primary prevention in many otherwise healthy individuals, including those who are physically active, is increasing.
• There is conflicting evidence regarding the relationship between statin use and musculoskeletal conditions. Given the rising disability associated with musculoskeletal conditions, understanding predisposing factors, including medication-related exposures, deserves further attention.

Medication-related exposures mean that there is a question that the medication is causing joint pain problems.

• Patients enrolled in a regional military healthcare system between 2003 and 2012 were evaluated in this retrospective cohort study.
• A propensity score was generated to match statin-users and nonusers using 115 baseline characteristics. Outcomes included ICD-9 diagnoses codes for the Agency for Healthcare Research and Quality disease categories of non-traumatic arthropathies, use-related injury, and undergoing rehabilitation. Primary analysis examined the outcomes in statin-users and nonusers after propensity score matching using conditional logistic regression analysis.

What were the findings of this study? “Statin use was associated with a significantly increased risk of non-traumatic arthropathies (wear and tear related joint replacement) and use-related injury.”

The statins were sending healthy, people who exercise to joint replacement.

Our results provide additional data that can inform patient and clinician conversations about the benefits and risks of statin use.

The subnote, of course, is through diet and exercise. Please see my article on The evidence that your diet is destroying your joints and will send you to a nursing home.

Tendon injury belongs to the less known side effects of some drugs. Such as fluoroquinolones and statins

Now let’s move on to the problems of tendinopathy. In late 2018, researchers in the Czech Republic reported these observations in the Czech Journal of Internal Medicine: (12)

“Tendon injury belongs to the less known side effects of some drugs, reported until recently only for glucocorticoids (steroid) and fluoroquinolones (antibiotics). To date, some other classes of drugs such as statins, aromatase inhibitors, and anabolic steroids, potentially causing tendon injury, have been added to the list. (In regard to tendon injury) Most often, the Achilles tendon is affected, however, nearly every tendon of the entire body may be affected.

Confusion and surprising findings – Do statins make tendons stronger? Weaker? No effect?

Researcher Pernilla Eliasson who is affiliated with the University of Copenhagen, Linköping University, Sweden, and the University of Rochester in New York led a team of researchers looking at the complexity of Simvastatin and atorvastatin and its relationship with tendon damage.

The research appearing in the online medical journal PLOS (13) examined the theory that Simvastatin and atorvastatin may have different potential for negative effects on tendons. Atorvastatin has been pointed out as one of the most harmful statins for tendon tissue while simvastatin has appeared with mixed findings.

• Some studies indicate that simvastatin has a negative impact on tendon tissue, while other studies suggest that simvastatin might even have a positive effect.
• Both atorvastatin and simvastatin had a negative effect on the tendon constructs in our study, however, the effect of simvastatin was in fact stronger and more pronounced.
  • This indicates that simvastatin indeed is harmful to tendon tissue and its extracellular matrix. However, high-dose atorvastatin treatment was the only treatment that had an effect on collagen content, and this was reduced by 22% compared to controls.
• Simvastatin had no effect on the collagen content to the researcher’s surprise. This indicates that there might be some differences in the mechanism of action on human tendon cells and extracellular matrix between these two statins. The range of the dosage of the two statins in clinical settings is similar, though the average dose for atorvastatin is slightly lower than the average dose for simvastatin. Higher doses of either of these two statins are toxic for tendon fibroblasts.

The researchers concluded that normal statin treatment of just seven days had such a detrimental effect on tendon tissue indicating that also long-term adaptations may occur. The more you take the statins, the worse the tendon damage.

In July 2023, researchers writing in the Orthopaedic Journal of Sports Medicine (14) made equal but differentiating findings in a group of  84,102 statin users. The types of included tendinopathy were as follows: (1) trigger finger, (2) radial styloid tenosynovitis (De Quervain’s tenosynovitis), (3) elbow epicondylitis, (4) rotator cuff tendinopathy, and (5) Achilles tendinitis.

The researchers agreed that “Statin treatments regardless of statin types were associated with a significantly greater risk of all types of tendinopathy development compared with no statin treatment.” Here is where they differed. These researchers suggested that “if a patient is going to have issues with tendinopathy from statin use, it will likely manifest in the first 180 days of use.” The longer you took statins, the less of a chance that it would have a detrimental effect on the tendons.

Summary

The question of whether short and long-term statin use is beneficial or detrimental to joint health continues. If this is a concern for you, discuss this with your doctor. If you have questions about your knee pain, you can get help and information from our Caring Medical Staff

References

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This article was update August 8, 2023

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