Marc Darrow, MD, JD.
There is a lot of controversy as to whether statin use for high cholesterol and metabolic disorders may cause accelerated or worsening osteoarthritis or protects against 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 between high cholesterol, weight, and the joint pain they suffer from. 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 cholesterol does is a subject of debate.
It cannot be significantly concluded whether hyperlipidemia and the use of statin are impacting osteoarthritis
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.”
Study: High cholesterol does not cause knee osteoarthritis
A February 2022 paper (2) says studies suggest an association between elevated total serum cholesterol, particularly low-density lipoprotein (LDL), and osteoarthritis. But the study also askes, is there one? That is what the researchers of this study asked. In this study, the researchers followed patients for seven years, as the researchers note repeated knee radiographs and magnetic resonance images (MRIs) were obtained, and knee symptoms were queried.
After excluding participants with baseline osteoarthritis, the researchers defined 2 sets of patients:
- those developing radiographic osteoarthritis (osteoarthritis showing up on films but not causing symptoms), and
- those developing symptomatic osteoarthritis (knee pain and radiographic osteoarthritis).
- In all the researchers studied 337 patients with incident symptomatic osteoarthritis and 283 patients with incident radiographic osteoarthritis. The mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL, nor HDL showed a significant association with radiographic or symptomatic osteoarthritis. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis, or worsening knee pain.
The possible relationship between use of statins and outcomes in knee osteoarthritis is limited.
An August 2019 study (3) asked this question and hoped to provide a definitive answer. The researchers of the study however could not. This is what they wrote in summary of their outcome: “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 (Lipitor).”
“These findings do not support the use of atorvastatin for the treatment of knee osteoarthritis.”
An August 2022 paper (4) People with knee osteoarthritis are at increased risk of cardiovascular disease, due to higher prevalence of risk factors including dyslipidaemia, where statins are commonly prescribed. However, the effect of statins on muscles and symptoms in this population is unknown. To explore an answer, researchers followed people aged 40-70 years (mean age 55.7 years, 55.6% female) with knee osteoarthritis who received atorvastatin (Lipitor) 40 mg daily or placebo. What the researchers found was that those with symptomatic knee osteoarthritis, despite a trend for more myalgia (muscle pain), displayed no clear evidence of an adverse effect of atorvastatin on muscles, including those most relevant to knee joint health.
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? In some patients muscle inflammation continued after the patients stopped using the statins.
A May 2020 case history (6) 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.
Do some statins reduce muscle pain or cause it? Research is inconclusive.
Many times a patient will suggest that the “right” statin will help ease muscle problems. Research says the right statin may not be the right statin. A March 2021 paper (7) observed: “Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells.” The statin users were divided into groups:
- Group 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic).
- Group 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic).
- Group 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg.
In the end, the study results did not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins.
The paradox. Statins cause muscle atrophy, but doctors do not want to discontinue them because discontinuance may mean higher risk of cardiovascular event.
Juggling stating use and muscle problems are the focus of a September 2022 paper. (8) In this paper the authors write:
“Statin-associated muscle symptoms are the most common form of statin intolerance and are associated with increased risk of cardiovascular events that manifest from statin underutilization and discontinuation.
The reported frequencies of Statin-associated muscle symptoms are divergent in the literature. (The authors) estimate the prevalence of Statin-associated muscle symptoms, namely all muscle symptoms temporally related to statin use but without regard to causality, to be about 10% (range 5% to 25%), and the prevalence of pharmacological Statin-associated muscle symptoms, specifically muscle symptoms resulting from pharmacological properties of the statin, to be about 1-2% (range 0.5% to 4%).
In clinical practice, Statin-associated muscle symptoms are likely to result from a combination of pharmacological and nonpharmacological effects, however this does not make the symptoms any less clinically relevant. Regardless of the etiology, Statin-associated muscle symptoms need to be addressed in accordance with patients’ preferences and experiences.
The authors the suggest a treatment strategy including
1) optimizing lifestyle interventions,
2) modulating risk factors that may contribute to muscle symptoms,
3) optimizing statin tolerability by dose reduction, decreased dosing frequency, or use of an alternate statin with more favorable pharmacokinetic properties, and
4) use of non-statins, emphasizing those with evidence for atherosclerotic risk reduction, either in combination with or in place of statin therapy depending on the patient’s circumstances. The focus of this clinical perspective is sustainable lipoprotein goal achievement, which is important for cardiovascular risk reduction.”
Slight or mild muscle pain is a common side effect of statins. For some people this pain is more severe and for a few people this may develop into rhabdomyolysis, a condition where muscle cells breakdown. The higher the dose of statins you take, the higher the risk of muscle pain or more serious condition.
The decision to remain on statins or seek out an alternative is up to you and your doctor.
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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 Schwager JL, Nevitt MC, Torner J, Lewis CE, Matthan NR, Wang N, Sun X, Lichtenstein AH, Felson D, Multicenter Osteoarthritis Study Group. Association of Serum Low‐Density Lipoprotein, High‐Density Lipoprotein, and Total Cholesterol With Development of Knee Osteoarthritis. Arthritis Care & Research. 2022 Feb;74(2):274-80.
3 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.
4 Lim YZ, Cicuttini FM, Wluka AE, Jones G, Hill CL, Forbes AB, Tonkin A, Berezovskaya S, Tan L, Ding C, Wang Y. Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: Post-hoc analysis of a randomised controlled trial. Frontiers in medicine. 2022 Aug 25;9:939800.
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 Stroie OP, Boster J, Surry L. Statin-induced immune-mediated necrotizing myopathy: an increasingly recognized inflammatory myopathy. Cureus. 2020;12(5):e7963.
7 Mueller AM, Liakoni E, Schneider C, Burkard T, Jick SS, Krähenbühl S, Meier CR, Spoendlin J. The risk of muscular events among new users of hydrophilic and lipophilic statins: an observational cohort study. Journal of general internal medicine. 2021 Sep;36(9):2639-47.
8 Warden BA, Guyton JR, Kovacs AC, Durham JA, Jones LK, Dixon DL, Jacobson TA, Duell PB. Assessment and management of statin-associated muscle symptoms (SAMS): A clinical perspective from the National Lipid Association. Journal of clinical lipidology. 2023 Jan 1;17(1):19-39.