Aromatase Inhibitor-Associated Distal Radioulnar Joint Instability and Tear of the Extensor Digiti Minimi: A Case Report.

ABSTRACT: The addition of aromatase inhibitors has improved cancer-related outcomes in postmenopausal patients with estrogen receptor-positive breast cancer. However, aromatase inhibitor can be associated with a constellation of adverse musculoskeletal effects that comprises bone loss, arthralgia, myalgia, and tendinopathy. This medication complication, known as aromatase inhibitor-associated musculoskeletal syndrome, can limit treatment tolerability in many patients because of the high prevalence of aromatase inhibitor-associated musculoskeletal syndrome among those on aromatase inhibitor. The hand and wrist are the most affected joints in aromatase inhibitor-associated musculoskeletal syndrome, with patients presenting with symmetric arthralgia, stiffness, and tendinopathy. Radioulnar joint subluxation with extensor tendon tear has not been previously reported in patients with aromatase inhibitor-associated musculoskeletal syndrome. This is a case report of a 72-yr-old breast cancer survivor on an aromatase inhibitor presenting with chronic dominant wrist pain, weakness, and 5th digit finger drop. An extensor digitorum minimi tendon tear and radioulnar instability were identified using diagnostic musculoskeletal ultrasonography. This case illustrates the utility of in-office ultrasonography combined with dynamic examination for the often underrecognized pathology associated with aromatase inhibitor-associated musculoskeletal syndrome in breast cancer survivors.

Testosterone replacement therapy is associated with increased odds of Achilles tendon injury and subsequent surgery: a matched retrospective analysis.

BACKGROUND: Prescription of testosterone replacement therapy (TRT) has increased in the United States in recent years, and though anabolic steroids have been associated with tendon rupture, there is a paucity of literature evaluating the risk of Achilles tendon injury with TRT. This study aims to evaluate the associative relationship between consistent TRT, Achilles tendon injury, and subsequent surgery. METHODS: This is a one-to-one matched retrospective cohort study utilizing the PearlDiver database. Records were queried for patients aged 35-75 who were prescribed at least 3 consecutive months of TRT between January 1, 2010 and December 31, 2019. Achilles tendon injuries and subsequent surgeries were identified using ICD-9, ICD-10, and CPT billing codes. Multivariable logistic regression was used to compare odds of Achilles tendon injury, Achilles tendon surgery, and revision surgery, with a p-value < 0.05 representing statistical significance. RESULTS: A sample of 423,278 patients who filled a TRT prescription for a minimum of 3 consecutive months was analyzed. The 2-year incidence of Achilles tendon injury was 377.8 (95% CI, 364.8-391.0) per 100,000 person-years in the TRT cohort, compared to 245.8 (95% CI, 235.4-256.6) in the control (p < 0.001). The adjusted analysis demonstrated TRT to be associated with a significantly increased likelihood of being diagnosed with Achilles tendon injury (aOR = 1.24, 95% CI, 1.15-1.33, p < 0.001). Of those diagnosed with Achilles tendon injury, 287/3,198 (9.0%) of the TRT cohort subsequently underwent surgery for their injury, compared to 134/2,081 (6.4%) in the control cohort (aOR = 1.54, 95% CI, 1.19-1.99, p < 0.001). CONCLUSIONS: There is a significant association between Achilles tendon injury and prescription TRT, with a concomitantly increased rate of undergoing surgical management. These results provide insight into the risk profile of TRT and further research into the science of tendon pathology in the setting of TRT is an area of continued interest.

Pectoralis major rupture in body builders: a case series including anabolic steroid use.

BACKGROUND: Rupture of the pectoralis major (PM) muscle is a rare injury, with increasing incidence over the last decades, mainly due to participation in weightlifting and contact sports. Surgical management of PM injuries has been related with superior functional outcome, faster return to activities, better cosmesis and higher level of patients' satisfaction. The aim of the study is to present our experience in the management of this rare clinical entity and to correlate the use of anabolic steroids in the occurrence of the injury and the impact of type of injury, method of reconstruction and anabolic steroids on the post-operative outcome. CASES: We present a series of six male bodybuilding athletes who sustained PM rupture during weightlifting. We recorded the location & type of injury, the history and type of anabolic steroids use, the method of repair and the post-operative outcome. TREATMENT AND OUTCOMES: The mean follow-up period was 16 (12-24) months. All patients treated surgically had excellent results according to Bak criteria and returned to full activity within 5.4 (5-7) months following surgical reconstruction. No post-operative complications were recorded, despite the continued use of anabolic steroids, however one patient died from myocardial infarction within a year of surgical treatment. CONCLUSIONS: PM rupture is an injury with increasing incidence within bodybuilding athletes probably not related to the dominance of the limb. Fixation of the tendon with suture anchors results in excellent clinical outcome and patient's satisfaction postoperatively regardless the chronicity of the repair. Our observations in these cases suggest that anabolic steroids use may contribute to the injury due to an excessive upward adjustment of the athlete's goals in lifting weights and moreover the continuation of administration even in the recovery period does not seem to have a negative effect either on the time or on the level of adequate functional recovery postoperatively.

Outpatient fluoroquinolone use in relation to European Medicines Agency's recommendation: An Estonian nationwide drug utilization study.

PURPOSE: To determine possible changes in prescribing of fluoroquinolones in relation to the European Medicines Agency's (EMA) recommendation in October 2018. METHODS: We conducted a nationwide time-series study on outpatient use of fluoroquinolones during January 2016-June 2021 in Estonia. Joinpoint regression was used to identify change points over time. Several subgroup analyses by prescriber specialty, indication group, risk factors for tendon injury, aortic aneurysm/dissection or heart valve regurgitation/incompetence and the prescribing of other antibiotics were performed. RESULTS: During the study period 236 989 prescriptions of fluoroquinolones were dispensed to 142 659 persons. The number of episodes per month declined from 3780 (2.9/1000 inhabitants) to 2570 (1.9/1000 inhabitants). We identified three change points with four different trend segments: from January 2016 to November 2018 monthly percent change (MPC) -0.4%, from November 2018 to June 2019 MPC -2.5%, from June 2019 to July 2020 MPC 1.7% and from July 2020 to June 2021 MPC -3.3%. Prescribing for indications which were removed or restricted by EMA's recommendation comprised a small proportion of all fluoroquinolone episodes -2.8% and 6.3%, respectively. The risk factors for tendon injury and for cardiac disorders (aortic aneurysm/dissection or heart valve regurgitation/incompetence) were present in 46.4% and 57.8% episodes of fluoroquinolone users, respectively. No changes in the trend of prescribing to users with risk factors was detected. CONCLUSIONS: The EMA's recommendation may have contributed to the greater decline in the use of fluoroquinolones. However, there is still a high proportion of users with predisposing factors for tendon injury and serious cardiac disorders.

[Achilles tendinopathy in a hemodialysis patient complicated by rupture of the Achilles tendon due to self-medication with ciprofloxacin: about a case]. / Tendinopathie achilléenne compliquée d´une rupture du tendon d´Achille consécutives à une automédication par la ciprofloxacine chez une hémodialysée: à propos d´un cas.

This study aims to remind clinicians of fluoroquinolone-related tendinopathies. They are rare side effects, but which can result in functional disability. We report the case of a 79-year-old woman with a 11-year history of haemodialysis who had sudden left ankle pain and functional impairment in the ipsilateral member on day 5th after self-medication with ciprofloxacin. Comorbidities included chronic gonarthrosis, secondary hyperparathyroidism and ischemic heart disease. The diagnosis of bilateral Achilles tendinopathy and rupture of the left Achilles tendon was retained due to clinical features and confirmed by ultrasound of ankles. Ciprofloxacin-associated tendon rupture was evaluated using the French method of accountability for drug unexpected side effects or toxicity. Tendon rupture management was based on surgery followed by functional rehabilitation program with satisfactory outcome. The frequency of fluoroquinolone-related tendinopathies ranges from 15 to 20 accidents per 100,000 subjects treated, a third of whom are complicated by tendon rupture. Incidence is related to age, affecting mainly people > 60 years and involving tissular aging. Pefloxacin and ciprofloxacin are the most offending molecules. In our study, the delay in the onset of symptoms on day 5 after self-medication was consistent with literature. We detected some common contributing factors including chronic renal failure, hemodialysis and the assumption of statins and corticosteroids. Fluoroquinolone-related tendinopathies are characterized by common clinical features which allow diagnosis. They mostly affect Achilles tendon. They are bilateral in 40-66% of cases. Tendon rupture is the main complication. Management is based on surgery. It allows to restore anatomy and to prevent detrimental functional disability. We here report a rare but potentially serious fluoroquinolones-related side effect, exposing the patient to the risk of functional disability. Advanced age, chronic renal failure, chronic haemodialysis, concomitant use of statins and corticosteroids are common contributing factors confirmed in this study. Hemodialysis patients constitute a population at risk; hence the importance of remote monitoring after treatment with these molecules.

Health service use and costs associated with fluoroquinolone-related tendon injuries.

The aim of this study was to assess costs and health service use associated with tendon injuries after the use of fluoroquinolone antimicrobials in Finland during 2002-2012. This retrospective observational study included data from the Finnish Pharmaceutical Insurance Pool's pharmaceutical injury claims. In total, 145 compensated claimants aged ≥18 years presenting tendon injuries after the use of fluoroquinolones (FQs) were included in the study. Outcomes of interest were the number of outpatient visits to primary, secondary, tertiary, and private healthcare services, hospital days, rehabilitation and their costs. Regression models were used to analyze the impact of patient characteristics on hospital days, as well as the relationship between patient characteristics and tendon ruptures. Direct costs of a tendon injury averaged 14,800€ and indirect costs were estimated to be 9,077€ for employed claimants. Fifty-one percent of the claimants were hospitalized, with an average duration of 21 days. Hospitalization was the costliest form of health service use with an average of 9,915€ per hospital episode. Hospital days and direct costs increased with the severity of the injury. Tendon ruptures, in particular bilateral ruptures, required substantially more hospital days and their direct costs were significantly higher than those of uncomplicated tendinitis. Concurrent use of oral corticosteroids and increasing age were associated with a higher likelihood of tendon ruptures. Although rare, FQ-related tendon injuries can result in considerable costs and health service use. Medical staff should remain vigilant when prescribing FQs, especially in groups at increased risk for tendon injuries.

Association Between Third-Generation Fluoroquinolones and Achilles Tendon Rupture: A Self-Controlled Case Series Analysis.

PURPOSE: We investigated whether use of third-generation fluoroquinolones is associated with occurrence of Achilles tendon rupture using a case series analysis in which patients served as their own control. METHODS: We used administrative claims data to identify residents in a single Japanese prefecture who were enrolled in National Health Insurance and Elderly Health Insurance from April 2012 to March 2017 and experienced Achilles tendon rupture after receiving an antibiotic prescription. Antibiotics were categorized into 3 groups: first- and second-generation fluoroquinolones, third-generation fluoroquinolones, and nonfluoroquinolones. We used a conditional Poisson regression model to estimate the incidence rate ratio (IRR) of Achilles tendon rupture during the antibiotic exposure period relative to the nonexposure period for each patient. An exposure period was defined as 30 days from start of the prescription. RESULTS: Analyses were based on 504 patients with Achilles tendon rupture who had received antibiotic prescriptions. Risk of rupture was not significantly elevated during exposure to third-generation fluoroquinolones (IRR = 1.05; 95% CI, 0.33-3.37) and nonfluoroquinolones (IRR = 1.08; 95% CI, 0.80-1.47). In contrast, risk was significantly elevated during exposure to first- and second-generation fluoroquinolones (IRR = 2.94; 95% CI, 1.90-4.54). Findings were similar across subgroups stratified by sex and by recent corticosteroid use. CONCLUSIONS: Our analysis showed that third-generation fluoroquinolone use was not associated with an increased risk of Achilles tendon rupture. These antibiotics may be a safer option for patients in whom this risk is elevated, such as athletes.

Fluoroquinolone Antibiotics and Tendon Injury in Adolescents.

OBJECTIVES: To estimate the association between fluoroquinolone use and tendon injury in adolescents. METHODS: We conducted an active-comparator, new-user cohort study using population-based claims data from 2000 to 2018. We included adolescents (aged 12-18 years) with an outpatient prescription fill for an oral fluoroquinolone or comparator broad-spectrum antibiotic. The primary outcome was Achilles, quadricep, patellar, or tibial tendon rupture identified by diagnosis and procedure codes. Tendinitis was a secondary outcome. We used weighting to adjust for measured confounding and a negative control outcome to assess residual confounding. RESULTS: The cohort included 4.4 million adolescents with 7.6 million fills for fluoroquinolone (275 767 fills) or comparator (7 365 684) antibiotics. In the 90 days after the index antibiotic prescription, there were 842 tendon ruptures and 16 750 tendinitis diagnoses (crude rates 0.47 and 9.34 per 1000 person-years, respectively). The weighted 90-day tendon rupture risks were 13.6 per 100 000 fluoroquinolone-treated adolescents and 11.6 per 100 000 comparator-treated adolescents (fluoroquinolone-associated excess risk: 1.9 per 100 000 adolescents; 95% confidence interval -2.6 to 6.4); the corresponding number needed to treat to harm was 52 632. For tendinitis, the weighted 90-day risks were 200.8 per 100 000 fluoroquinolone-treated adolescents and 178.1 per 100 000 comparator-treated adolescents (excess risk: 22.7 per 100 000; 95% confidence interval 4.1 to 41.3); the number needed to treat to harm was 4405. CONCLUSIONS: The excess risk of tendon rupture associated with fluoroquinolone treatment was extremely small, and these events were rare. The excess risk of tendinitis associated with fluoroquinolone treatment was also small. Other more common potential adverse drug effects may be more important to consider for treatment decision-making, particularly in adolescents without other risk factors for tendon injury.

Asynchronous Bilateral Achilles Tendon Rupture with Selective Androgen Receptor Modulators: A Case Report.

CASE: A 36-year-old male competitive powerlifter sustained asynchronous bilateral Achilles tendon ruptures after using 2 types of selective androgen receptor modulators (SARMs). Both tendon ruptures occurred near the myotendinous junction and were treated with open surgical repair and an initial period of immobilization followed by progressive weightbearing and rehabilitation; no postoperative complications were observed. CONCLUSION: Previous studies have reported that anabolic androgenic steroids have a deleterious impact on tendon structure and function. This case suggests that SARM compounds may also predispose users to Achilles tendon rupture.

Rotura del tendón extensor del dedo de la mano. ¿Un efecto secundario del tratamiento con estatinas? / Finger extensor tendon tear. A secondary effect of treatment with statins?

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Multiple tendon ruptures associated with statin therapy.

We present the case of a 44-year-old physician with familial heterozygous hypercholesterolemia who experienced multiple tendon ruptures during 19 years of statin therapy and no tendon injuries in the 5 years since statins were discontinued. Statins may deleteriously affect tendon extracellular matrix by inhibiting synthesis of matrix metalloproteinases and cell cycle regulatory proteins. Clinicians should be aware of this possible association between statins and tendinopathy.

Posible rotura tendinosa espontánea relacionada con el uso de atorvastatina / Possible spontaneous tendon rupture related to the use of atorvastatin

La rotura espontánea del tendón cuadricipital (REC) es una lesión de escasa incidencia cuya etiología se ha relacionado con el uso de diferentes fármacos. Las estatinas son fármacos que se han asociado a la aparición de reacciones adversas que afectan al sistema músculo-esquelético, aunque la relación entre su uso y las roturas tendinosas es controvertida. Presentamos 2 casos de REC de pacientes en tratamiento con atorvastatina. Este trabajo contribuye a aumentar la literatura publicada sobre la posible asociación entre el uso de atorvastatina y la aparición de REC

Spontaneous quadriceps tendon rupture (SQTR) is a lesion of low incidence whose etiology has been related to the use of different drugs. Statins have been associated with the appearance of adverse reactions that affect the musculoskeletal system. However, the relationship between their use and tendon rupture remains controversial. We present 2 cases of SQTR in patients taking atorvastatin. This work contributes to increase the published literature of the association between use of atorvastatin and appearance of SQTR

Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.

PURPOSE: Tendinopathy is a known adverse reaction associated to fluoroquinolones, but a meta-analysis was not yet published. The aim of this study was to conduct a systematic review and a meta-analysis of the scientific evidence evaluating the risk of tendon injury associated with fluoroquinolones. METHODS: A literature search was conducted to identify observational studies which reported results on the risk of Achilles tendon rupture (ATR), risk of Achilles tendinitis (AT), or risk of any tendon disorders (ATD). A meta-analysis was performed by pooling odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS: Fifteen studies were included in the meta-analysis. Treatment with fluoroquinolones was associated with an increased risk of ATR (OR 2.52 (95% CI 1.81-3.52), p < 0.001, I2 = 76.7%), an increased risk of AT (OR 3.95 (95% CI 3.11-5.01), p < 0.001, I2 = 0%), and increased risk of ATD (OR 1.98 (95% CI 1.62-2.43), p < 0.001, I2 = 84.5%). The initial risk estimates remained statistically significant among patients aged ≥ 60 years old. Risk estimates did not significantly change after depending on the concomitant use of corticosteroids or studies methodological quality assessment. The analysis according to the type of fluoroquinolones was only possible for ATR, which were ofloxacin and norfloxacin were found to increase the risk of this outcome, but not ciprofloxacin and levofloxacin. CONCLUSIONS: The results of this meta-analysis confirm the risk of tendon injuries associated with fluoroquinolones. Older age and concomitant use of corticosteroids seem to be additional risk factors for tendinopathy.

Molecular changes to tendons after collagenase-induced acute tendon injury in a senescence-accelerated mouse model.

BACKGROUND: Aging impairs tendon healing and is a potential risk factor for chronic tendinitis. During normal aging, tendons undergo structural and biomechanical degenerative changes, accompanied by a reduction in the number of tenocytes and changes to their properties. However, molecular changes in aged tendons under inflammatory conditions are not well understood. The present study analyzed the molecular changes in collagenase induced acute tendon injury using a senescence-accelerated mouse (SAM) model. METHODS: SAMP6 mice were used as an aging animal model and SAMR1 mice were used as a control to represent a senescence-resistant inbred strain. All the mice used in the study were 40 weeks old. Collagenase I from Clostridium histolyticum (20 µL) was injected percutaneously to the tendon-bone junction of the Achilles tendon. Two weeks after treatment, the Achilles tendons were harvested and stained using Picrosirius Red to determine collagen expression. Real-time PCR was performed to analyze gene expression of IL-6, tenomodulin, type I and type II collagen, MMP-9, TIMP-1, and TIMP-2. RESULTS: Collagenase injection resulted in significantly higher gene expression of IL-6 but significantly lower tenomodulin expression compared with the control in SAMP6 and SAMR1 mice. In SAMP6 mice, gene expression of type III collagen and MMP-9 was significantly higher in the collagenase-injected group compared with the control group. SAMP6 mice also showed lower expression of type I collagen, TIMP-1, and TIMP-2 in the collagenase-injected group compared with the control group. Picrosirius Red staining showed the highest expression of type III collagen in the collagenase-injected SAMP6 group compared with the other groups. CONCLUSIONS: The collagenase-injected SAMP6 group showed higher expression of IL-6, MMP-9, and type III collagen and lower expression of type I collagen, TIMP-1, and TIMP-2, which are known to suppress metalloproteinases. The results indicate that aging may lead to dysfunction of the tendon healing process after acute tendon injury.

Clinical implications of the association between fluoroquinolones and tendon rupture: The magnitude of the effect with and without corticosteroids.

AIMS: To estimate the relative, absolute and attributable risk of non-traumatic tendon rupture, at various sites, associated with use of fluoroquinolones, with and without concomitant corticosteroids. METHODS: We conducted cohort and nested case-control studies among fluoroquinolone users in the United Kingdom Clinical Practice Research Datalink Gold. We estimated the excess risk (cohort analysis) and odds ratios (ORs) (case control) of tendon rupture by fluoroquinolone (current, recent and past use versus unexposed) and corticosteroid (current versus unexposed) use. RESULTS: Among 740 926 patients with a fluoroquinolone prescription, 3957 cases of tendon rupture were identified. The excess risk due to current fluoroquinolone use was low: any tendon rupture 3.73 (95% confidence interval, CI, 2.08-5.39) per 10 000 person-years (PY) and Achilles tendon rupture 2.91 (1.71-4.11) per 10 000 PY. The excess risk of any tendon rupture was much higher for current concomitant fluoroquinolone and corticosteroid use versus corticosteroids alone: 21.2 (11.3-31.2) per 10 000 PY. In the case-control, OR (95% CI) among current fluoroquinolone users versus unexposed patients was elevated: any tendon rupture 1.60 (1.22-2.09), Achilles tendon 2.71 (1.76-4.17) and bicep tendon 1.53 (0.85-2.73). The risk of any tendon rupture was higher among women (OR 2.27 [1.54-3.34]), patients aged 60+ (OR 2.42 [1.74-3.37]), and concomitant corticosteroid use (OR 6.64 [3.99-11.1]). CONCLUSIONS: Fluoroquinolones increase the risk of Achilles tendon rupture and, to a lesser extent, bicep tendon rupture, but the attributable risk is low. The risk is materially increased with concomitant use of corticosteroids.

Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study.

BACKGROUND AND OBJECTIVE: Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure. METHODS: The UK Health Improvement Network primary care database was used to perform a nested case-control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated. RESULTS: Current fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25-2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11-4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78-48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures. CONCLUSIONS: Risk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.

[Drug induced tendon injury]. / Poskození slach vyvolané léky.

Tendon injury belongs to the less known side effects of some drugs, reported until recently only for glucocorticoids and fluoroquinolones. To date, some other classes of drugs such as statins, aromatase inhibitors, anabolic steroids, potentially causing tendon injury, have been added to the list. The authors discuss the most common clinical presentations, diagnosis, and management as well as latest experimental data regarding this issue. The most often, the Achilles tendon is affected, however, nearly every tendon of the entire body may be affected. Tendon rupture or drug induced tendinopathy should be strongly considered in those who have a tendon injury and have recently taken these drugs.Key words: anabolic steroids - aromatase inhibitors - fluoroquinolones - glucocorticoids - statins - tendon injury.