Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation

• Published in: PloS one Vol. 9; no. 12; p. e115595
• Main Authors: Ibrahim, Nurul 'Izzah, Khamis, Mohd Fadhli, Mod Yunoh, Mohd Faridz, Abdullah, Shahrum, Mohamed, Norazlina, Shuid, Ahmad Nazrun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.12.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antilipemic agents; Bioavailability; Biocompatibility; Biology and Life Sciences; Biomechanical Phenomena; Biomechanics; Bone density; Bone healing; Callus; CAT scans; Cholesterol; Combined treatment; Computed tomography; Disease Models, Animal; Drug delivery; Drug Delivery Systems; Drug dosages; Drug Therapy, Combination; Engineering; Estrogens; Female; Fracture Healing - drug effects; Fractures; Fractures (Injuries); Healing; Humans; Injection; Lovastatin; Lovastatin - administration & dosage; Lovastatin - therapeutic use; Medicine and Health Sciences; Menopause; Metabolism; Metaphysis; Osteoporosis; Osteoporosis, Postmenopausal - complications; Osteoporosis, Postmenopausal - diagnostic imaging; Ovariectomy; Pharmacology; Post-menopause; Postmenopausal women; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Statins; Studies; Tensile Strength - drug effects; Tibial Fractures - complications; Tibial Fractures - diagnostic imaging; Tibial Fractures - drug therapy; Tocotrienols - administration & dosage; Tocotrienols - therapeutic use; Treatment Outcome; Ultrasound; X-Ray Microtomography - methods; Kuala Lumpur Malaysia; Selangor Malaysia; Malaysia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0115595

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.