Does high cholesterol or statin use accelerate osteoarthritis?

Marc Darrow MD, JD.

There is a lot of controversy as to whether stains use or high cholesterol causes accelerated or worsening osteoarthritis. We do see many patients who have weight challenges and cholesterol problems, among many. They have osteoarthritis and they have cholesterol problems being managed by statin use. They often ask if there is a connection. Certainly not being in the best shape can worsen joint pain. That is generally understood. For those seeking answers to whether the statins are causing muscle and joint problems (a well known side effect) or whether high cholestrol does is a subject of debate.

A June 2021 paper (1) wrote: “Osteoarthritis is progressive wear and tear disease that affects multiple joints by causing structural damage to joints. Although there is no validated positive conclusion, research indicates that metabolic syndrome (a group of conditions that put you at higher risk factor for heart disease, stroke and type 2 diabetes) can affect the development and progression of osteoarthritis. One such metabolic risk factor is hyperlipidemia (high cholesterol).”

In this paper the researchers assessed 13 studies to explore if there is an effect of hyperlipidemia and statin use on the progression of osteoarthritis. Although hyperlipidemia can be a risk factor, it cannot be significantly concluded whether hyperlipidemia and the use of statin are impacting osteoarthritis since further research is needed to significantly conclude either the positive or negative correlation of hyperlipidemia and statin use on osteoarthritis and its progression.”

Statins joint pain

Does research suggests statins may help knee osteoarthritis?

An August 2019 study (2) ask this question and hoped to provider a definitive answer. The researchers could not. This is what they wrote: “Statins have several (beneficial) effects, but the literature regarding the possible relationship between use of statins and outcomes in knee osteoarthritis  is limited. . . The effect of statin use on knee osteoarthritis outcomes remains unclear, although in our study, a significantly lower risk of developing knee pain was observed in individuals using statins for more than five years and those using atorvastatin.”

“These findings do not support the use of atorvastatin for the treatment of knee osteoarthritis.”

A November 2021 study (3) tried to determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis. In this study participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) (151 patients) or matching placebo (153 patients). The results were: “Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over two years in patients with symptomatic knee osteoarthritis. These findings do not support the use of atorvastatin for the treatment of knee osteoarthritis.

Inconclusive results of statin use

As September 2021 paper (5) reaffirmed that results of statin use for joint pain and osteoarthritis remain inconclusive. Several traditional risk factors of atherosclerosis such as age, obesity, and altered lipid metabolism are shared with osteoarthritis. Metabolic abnormalities and atheromatous vascular disease are linked with systemic inflammation and progression of osteoarthritis . Hence, treatment of osteoarthritis with statins is expected to improve metabolic abnormalities and prevent osteoarthritis progression. Many studies which have addressed this issue found inconsistent results.

Do statins cause muscle pain by causing muscle inflammation?  inflammation in the muscles. What is worse is that the muscle inflammation continued after the patients stopped using the statins.

A May 2020 case history (4) suggested not only did statins cause muscle inflammation but that the muscle inflammation problem continued even after the statins were stopped because of the muscle pain side-effect.

The doctors of this paper described the case of a 59-year-old man with a prior history of statin intolerance (the man did not tolerate the statins and among his symptoms were muscle related pain and discomfort.

Look what happened next to this man. The statins gave him muscle pain, it lasted 10 months after he stopped using statins. To get this situation under control the man was subjected to high-dose glucocorticoids which did lead to a rapid clinical improvement, although the patient relapsed upon tapering. Remission was attained at three months after combination therapy with azathioprine, intravenous immunoglobulin, and a prolonged prednisone taper.

Injections versus statins – Hyaluronic acid injection vs. atorvastatin

A June 2020 study (6) compared atorvastatin to Hyaluronic acid in knee osteoarthritis patients. They found that the hyaluronic acid group had significant improvements over atorvastatin in pain symptoms and physical function in the second month after treatment. But this improvement did not last through the following months.

Do Statins make joint pain worse?

A 2020 paper wrote the following (7) : “Statins may play a potentially protective role in osteoarthritis due to their anti-inflammatory effects and these results were confirmed in animal models of osteoarthritis. However, our meta-analysis of 11 articles with more than 670000 participants confirmed that statin use may not be associated with a reduced risk of incidence or progression of osteoarthritis, although we detected that atorvastatin and rosuvastatin have opposite effects on osteoarthritis.

High cholesterol and its subsequent management with statins as a cholesterol lowering medication.

This research was continued and published in a November 2021 paper (8) which assessed the effects of atorvastatin on preventing knee cartilage loss in  patients with symptomatic knee osteoarthritis

In this study 151 participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) and 152 people received a placebo. The measure to test effectiveness was an annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI).

  • The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups.
  • There were no significant differences in the progression of cartilage defects or progression of bone marrow lesions.
  • Moreover, there were no significant differences in change in pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups.
  • Study conclusion: “Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee osteoarthritis. These findings do not support the use of atorvastatin for the treatment of knee osteoarthritis.

Do statins cause muscle pain?

A phenomena reported by many patients to their doctors is that of statin-induced muscle fatigue and muscle pain. As studied for their impact of stopping the progression of osteoarthritis, research is also looking at side-effects statins may cause including muscle pain and fatigue.

References

1 Nukala S, Puvvada SR, Luvsannyam E, Patel D, Hamid P. Hyperlipidemia and Statin Use on the Progression of Osteoarthritis: A Systematic Review. Cureus. 2021 Jun 28;13(6).
2 Veronese N, Koyanagi A, Stubbs B, Cooper C, Guglielmi G, Rizzoli R, Schofield P, Punzi L, Al‐Daghri N, Smith L, Maggi S. Statin use and knee osteoarthritis outcomes: a longitudinal cohort study. Arthritis care & research. 2019 Aug;71(8):1052-8.
3 Wang Y, Jones G, Hill C, Wluka AE, Forbes AB, Tonkin A, Hussain SM, Ding C, Cicuttini FM. Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo‐Controlled Trial. Arthritis & Rheumatology. 2021 Nov;73(11):2035-43.
4 Stroie OP, Boster J, Surry L. Statin-Induced Immune-Mediated Necrotizing Myopathy: An Increasingly Recognized Inflammatory MyopathyCureus. 2020;12(5):e7963.
5 Heidari B, Babaei M, Yosefghahri B. Prevention of Osteoarthritis Progression by Statins, Targeting Metabolic and Inflammatory Aspects: A Review. Mediterranean journal of rheumatology. 2021 Sep;32(3):227.
6 Jokar MH, Mirfeizi Z, Zarei H, Hashemzadeh K. Intra-articular hyaluronic acid injection vs. atorvastatin; which treatment is more effective in controlling symptoms of knee osteoarthritis? A clinical trial. Acta Reumatológica Portuguesa. 2020 Apr 1;45(2).
7 Wang J, Dong J, Yang J, Wang Y, Liu J. Association between statin use and incidence or progression of osteoarthritis: meta-analysis of observational studies. Osteoarthritis and Cartilage. 2020 Sep 1;28(9):1170-9.
8 Wang Y, Jones G, Hill C, Wluka AE, Forbes AB, Tonkin A, Hussain SM, Ding C, Cicuttini FM. Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo‐Controlled Trial. Arthritis & Rheumatology. 2021 Nov;73(11):2035-43.

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