Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin.
OBJECTIVE
Accumulating clinical evidence indicates the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use. This experimental study was designed to evaluate and compare the biomechanical and histopathological effects of the three most commonly prescribed statins (simvastatin, atorvastatin and rosuvastatin) on the Achilles tendon in rats.


METHODS
Statins were administered by gavage to rats at daily doses of 20 and 40 mg/kg for 3 weeks. One week later, the Achilles tendons were dissected and their biomechanical properties, including ultimate tensile force, yield force and elastic modulus, were determined. The samples were stained with haematoxylin-eosin and examined under a light microscope. The biomechanical properties of the tibia were tested by three-point bending test. Bone mineral density (BMD) and the lengths of tibias were measured by computed tomography.


RESULTS
All the statins caused deterioration of the biomechanical parameters of the Achilles tendon. Histopathological analysis demonstrated foci of dystrophic calcification only in the statin-treated groups. However, the number and the total area of calcific deposits were similar between the statin groups. The biomechanical parameters of tibias were improved in all the statin groups. BMD in the statin-treated groups was not significantly different from the control group.


CONCLUSIONS
All the statins tested are associated with calcific tendinopathy risk of which full awareness is required during everyday medical practice. However, statin-associated improvement of bone biomechanical properties is a favourable feature which may add to their beneficial effects in atherosclerotic cardiovascular disease, especially in the elderly.
Department of Pharmacology, Faculty of Medicine, University of Yeditepe, Istanbul, Turkey.
Ferda
F
Kaleağasıoğlu
Department of Orthopaedic Surgery, Faculty of Medicine, University of Kafkas, Kars, Turkey. ercan.olcay3809@gmail.com.|Department of Orthopaedic Surgery, Kanuni Sultan Suleyman Educational Hospital, Istanbul, Turkey. ercan.olcay3809@gmail.com.
Ercan
E
Olcay
Department of Pathology, Institute of Oncology, University of Istanbul, Istanbul, Turkey.
Vakur
V
Olgaç
D000125:Achilles Tendon / Q000473:pathology* / Q000503:physiopathology*; D000369:Aged, 80 and over; D000818:Animals; D000069059:Atorvastatin / Q000009:adverse effects; D001696:Biomechanical Phenomena; D015519:Bone Density; D002114:Calcinosis / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D017208:Rats, Wistar; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000009:adverse effects; D012422:Rupture, Spontaneous; D019821:Simvastatin / Q000009:adverse effects; D052256:Tendinopathy / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin
Achilles tendon; Atorvastatin; Biomechanics; Bone density; Calcific tendinopathy; Rosuvastatin; Simvastatin