Four cases of tendinopathy in patients on statin therapy

doi:10.1016/S1297-319X(01)00300-1

Joint Bone Spine

Volume 68, Issue 5, October 2001, Pages 430-433

https://doi.org/10.1016/S1297-319X(01)00300-1 Get rights and content

Abstract

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensor tenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.

Section snippets

Case reports

Three of the four cases reported here were presented at the National Meeting of the French Society for Rheumatology in May 2000 〚1〛. Since then, a fourth case has been recorded. Table I sumarizes these four cases.

Discussion

These are the first reported cases of tendinopathy in patients on statin therapy. Tendon rupture did not occur. Sports-related injury, severe long-standing familial hypercholesterolemia with xanthomas, hyperuricemia, and use of other medications known to induce tendinopathy, which are well-known risk factors for tendon disease, were absent in all four patients. One patient (case 3) had a history of contralateral Achilles tendinopathy 6 years earlier and another (case 4) was on long-term

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Cited by (64)

Finger extensor tendon tear. A secondary effect of treatment with statins?
2020, Semergen
Structural and biomechanical changes in the Achilles tendon after chronic treatment with statins
2015, Food and Chemical Toxicology
Citation Excerpt :
These injuries to the tendons are more often associated with the use of simvastatin and atorvastatin, the two most prescribed statins in the treatment of hypercholesterolemia (Marie et al., 2008; Maron et al., 2000). Some studies have also indicated that the Achilles tendon appears to be the main injured tendon (Beri et al., 2009; Carmont et al., 2009; Chazerain et al., 2001; Kirchgesner et al., 2014). The doses of statins used in this study were determined by allometric scaling (Pachaly and Brito, 2001).
Cases of tendinopathy and tendon ruptures have been reported as side effects associated with statin therapy. This work assessed possible changes in the structural and biomechanical properties of the tendons after chronic treatment with statins. Wistar rats were divided into the following groups: treated with atorvastatin (A-20 and A-80), simvastatin (S-20 and S-80) and the group that received no treatment (C). The doses of statins were calculated using allometric scaling, based on the doses of 80 mg/day and 20 mg/day recommended for humans. The morphological aspect of the tendons in A-20, S-20 and S-80 presented signals consistent with degeneration. Both the groups A-80 and S-80 showed a less pronounced metachromasia in the compression region of the tendons. Measurements of birefringence showed that A-20, A-80 and S-80 groups had a lower degree of organization of the collagen fibers. In all of the groups treated with statins, the thickness of the epitenon was thinner when compared to the C group. In the biomechanical tests the tendons of the groups A-20, A-80 and S-20 were less resistant to rupture. Therefore, statins affected the organization of the collagen fibers and decreased the biomechanical strength of the tendons, making them more predisposed to ruptures.
Drug-induced tendinopathy: From physiology to clinical applications
2015, Revue du Rhumatisme (Edition Francaise)
La toxicité tendineuse d’origine médicamenteuse est un phénomène rare souvent sous-estimé. À ce jour, quatre classes thérapeutiques ont été principalement mises en cause. Les quinolones et la corticothérapie au long cours sont les plus connues, auxquelles il faut ajouter les statines et les inhibiteurs de l’aromatase. Les mécanismes physiopathologiques précis à l’origine de cette toxicité restent à établir. Des facteurs de risque ont été identifiés de manière formelle tels qu’un âge supérieur à 60 ans et une tendinopathie pré-existante ainsi qu’un effet de potentialisation lors de l’association de ces différentes classes thérapeutiques. Le délai moyen d’apparition des symptômes est variable, allant de quelques jours pour les quinolones, à plusieurs mois pour les statines voire plusieurs années pour la corticothérapie au long cours. L’atteinte est préférentiellement localisée aux tendons des membres inférieurs et particulièrement au corps du tendon calcanéen. Au cours de cette mise au point seront abordées dans une première partie l’anatomie du tendon, la physiopathologie et la séméiologie radiologique des tendinopathies. Puis dans une seconde partie seront développées successivement les principales caractéristiques des médicaments ayant une toxicité tendineuse.
Drug-induced tendinopathy: From physiology to clinical applications
2014, Joint Bone Spine
Drug-induced tendon toxicity is rare but often underestimated. To date, four main drug classes have been incriminated in tendinopathies. Quinolones and long-term glucocorticoids are the most widely known, but statins and aromatase inhibitors can also induce tendon damage. The specific pathophysiological mechanisms responsible for drug-induced tendinopathies remain unknown. Proven risk factors have been identified, such as age older than 60 years, pre-existing tendinopathy, and potentiation of toxic effects when several drug classes are used in combination. Mean time to symptom onset varies from a few days with quinolones to several months with statins and several years for long-term glucocorticoid therapy. The most common sites of involvement are the lower limb tendons, most notably the body of the Achilles tendon. The first part of this review discusses tendon anatomy and the pathophysiology and radiological manifestations of tendinopathies. The second part provides details on the main characteristics of each of the drugs classes associated with tendon toxicity.
Statins induce biochemical changes in the Achilles tendon after chronic treatment
2013, Toxicology
Citation Excerpt :
More recently, cases of tendinitis and tendon ruptures have been associated with the use of statins (Marie and Noblet, 2009). These complications have been observed in several tendons, including the distal biceps (Savvidou and Moreno, 2012), the patellar (Beri et al., 2009), the quadriceps (Nesselroade and Nickels, 2010; Rubin et al., 2011) and the Achilles tendons (Beri et al., 2009; Carmont et al., 2009; Chazerain et al., 2001), the latter of which are commonly injured (Marie et al., 2008). Simvastatin and atorvastatin are some of the most widely used statins in the treatment of hypercholesterolemia, and they are highly efficacious and tolerable (Maron et al., 2000).
Statins have been widely prescribed as lipid-lowering drugs and are associated with tendon rupture. Therefore, this study aimed to evaluate the possible biochemical changes in the Achilles tendon of rats after chronic treatment with statins. Dosages of statins were calculated using allometric scaling with reference to the 80 mg/day and 20 mg/day, doses recommended for humans. The rats were divided into the following groups: treated with simvastatin (S-20 and S-80), treated with atorvastatin (A-20 and A-80), and the control group that received no treatment (C). Measurements of low-density lipoprotein (LDL) in the plasma were performed. The levels of non-collagenous proteins, glycosaminoglycans (GAGs) and hydroxyproline were quantified. Western blotting for collagen I was performed, and the presence of metalloproteinases (MMPs)-2 and -9 was investigated through zymography. The concentration of non-collagenous proteins in S-20 was less than the C group. There was a significant increase in pro-MMP-2 activity in A-80 group and in active MMP-2 in S-20 group compared to the C group. A significant increase in latent MMP-9 activity was observed in both the A-80 and S-20 groups when compared to C group. In the A-20 group, there was a lower amount of collagen I in relation to C group. In addition, a higher concentration of hydroxyproline was found in the S-20 group than the C group. The analysis of GAGs showed a significant increase in the A-20 group when compared to C group. The treatment induced remarkable alterations in the Achilles tendon and the response of the tissue seems to depend of the used statin dosage. The presence of MMP-2 and MMP-9 is evidence of the degradation and remodeling processes in the extracellular matrix of the tendons. Our results show that statins induce imbalance of extracellular matrix components and possibly induce microdamage in tendons.
Unusual clinical presentation of a partial tibialis anterior rupture
2012, Annals of Physical and Rehabilitation Medicine
Citation Excerpt :
Tendon rupture is often secondary to open and sometimes closed trauma, usually associated to tibial fracture [2,7]. More rarely, it can occur spontaneously under medication (fluoroquinolones and statins), or because of psoriasis and gout [1,3,9,12]. In addition, there was an avascular area in the front middle-half of the TA, considered as an important risk factor of the degenerative process.
Subcutaneous rupture of the tibialis anterior tendon is rare. Diagnosis is usually clear. The essential clinical symptoms are progressively: footdrop gait, loss of ankle flexion strength, ankle foot pain and claw toes. But the occurrence of an asymptomatic time period between the injury and the onset of clinical signs can make the diagnosis more difficult. MRI is the gold standard examination for tendons injuries and associated bone and joints damages. Surgical exploration confirms MRI findings. It constitutes the treatment of choice for tibialis anterior tendon rupture. Surgical or functional techniques used have an impact on the design of the rehabilitation program, essential step in the care management of these injuries. It avoids postoperative tendon adhesions and their functional consequences. We report here a case of a man presenting with footdrop gait as the only clinical symptom.
La rupture sous-cutanée du tendon du tibialis anterior est rare. Son diagnostic ne pose souvent pas de difficulté. Les signes cliniques sont parlants et consistent en l’installation d’un steppage, d’un déficit de la flexion dorsale de la cheville, de douleurs de la face antérieure de la cheville et du pied et d’une attitude des orteils en griffe. Cependant, la survenue d’un intervalle libre entre le traumatisme et l’installation des signes cliniques peut amener à une discussion diagnostique. Dans ce cas, l’IRM constitue un excellent examen pour poser le diagnostic de la lésion tendineuse et rechercher d’éventuelles lésions associées des structures osseuses et articulaires. L’exploration chirurgicale confirme les données de l’IRM et permet de traiter la rupture du tendon du tibialis anterior. La technique utilisée conditionne la rééducation fonctionnelle qui reste fondamentale dans la prise en charge de cette lésion. Elle permet d’éviter les adhérences et les conséquences fonctionnelles. Nous rapportons ici le cas d’un patient se présentant pour l’exploration d’un steppage isolé.

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^*: This work was presented at the Fifth National Meeting of the French Society for Rheumatology, Bordeaux, France, May 2000

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CASE REPORTFour cases of tendinopathy in patients on statin therapy**

Abstract

Section snippets

Case reports

Discussion

Toxicol Appl Pharmacol

Trois cas de tendinopathies induites par une statine

Rev Rhum 〚Ed Fr〛

Imputabilité des effets inattendus ou toxiques des médicaments. Actualisation de la méthode utilisée en France

Thérapie

Statin's tendinitis

Thérapie

Randomised trial of cholesterol lowering in 4, 444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

Lancet

CASE REPORT
Four cases of tendinopathy in patients on statin therapy^