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

Nurul Izzah Ibrahim, Mohd Fadhli Khamis, Mohd Faridz Mod Yunoh, Shahrum Abdullah, Norazlina Mohamed, Ahmad Nazrun Shuid

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 mg/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.

Original languageEnglish
Article numbere115595
JournalPLoS One
Volume9
Issue number12
DOIs
Publication statusPublished - 19 Dec 2014

Fingerprint

Tocotrienols
lovastatin
micro-computed tomography
Lovastatin
tocotrienols
Fracture Healing
osteoporosis
Osteoporosis
Tomography
Bony Callus
callus
injection
Rats
Injections
tibia
Tibia
rats
Bone
conjugated estrogens
bones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model : Micro-computed tomography and biomechanical evaluation. / Ibrahim, Nurul Izzah; Khamis, Mohd Fadhli; Yunoh, Mohd Faridz Mod; Abdullah, Shahrum; Mohamed, Norazlina; Shuid, Ahmad Nazrun.

In: PLoS One, Vol. 9, No. 12, e115595, 19.12.2014.

Research output: Contribution to journalArticle

@article{2e143e8235d2493bb3e997f922e1fd0d,
title = "Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: Micro-computed tomography and biomechanical evaluation",
abstract = "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 mg/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.",
author = "Ibrahim, {Nurul Izzah} and Khamis, {Mohd Fadhli} and Yunoh, {Mohd Faridz Mod} and Shahrum Abdullah and Norazlina Mohamed and Shuid, {Ahmad Nazrun}",
year = "2014",
month = "12",
day = "19",
doi = "10.1371/journal.pone.0115595",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model

T2 - Micro-computed tomography and biomechanical evaluation

AU - Ibrahim, Nurul Izzah

AU - Khamis, Mohd Fadhli

AU - Yunoh, Mohd Faridz Mod

AU - Abdullah, Shahrum

AU - Mohamed, Norazlina

AU - Shuid, Ahmad Nazrun

PY - 2014/12/19

Y1 - 2014/12/19

N2 - 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 mg/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.

AB - 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 mg/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.

UR - http://www.scopus.com/inward/record.url?scp=84919683732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919683732&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0115595

DO - 10.1371/journal.pone.0115595

M3 - Article

C2 - 25526611

AN - SCOPUS:84919683732

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e115595

ER -