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 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.
Highlights
The aging population has persistently increased, resulting into more and more middle-aged and senile patients affected by age-related or postmenopausal osteoporosis [1].The prevalence of osteoporosis increases dramatically with aging in women, from 5% at 50 years old to 50% at 85 years old [2]
Osteoporosis is becoming a major health problem as it is associated with compromised stability and reduced mobility of the patients [3].Osteoporosis is defined as a condition where the bone mineral density (BMD) falls below 2.5 standard deviations of peak mass as measured by Dual-Energy X-ray Absorptiometry (DXA) [4]
For mBMD measurement, the Ovx+TT+Lov and Sham groups showed significantly higher mBMD compared to the OvxC group(p,0.05).There were no other significant differences among the various treatment groups for all the micro-CT variables (Fig. 5)
Summary
The aging population has persistently increased, resulting into more and more middle-aged and senile patients affected by age-related or postmenopausal osteoporosis [1].The prevalence of osteoporosis increases dramatically with aging in women, from 5% at 50 years old to 50% at 85 years old [2]. Osteoporosis is becoming a major health problem as it is associated with compromised stability and reduced mobility of the patients [3].Osteoporosis is defined as a condition where the bone mineral density (BMD) falls below 2.5 standard deviations of peak mass as measured by Dual-Energy X-ray Absorptiometry (DXA) [4]. It can be characterized by low bone mass and microarchitectural deterioration of bone tissue, which may lead to bone fragility fracture [5]. In the final or remodeling phase, the callus and vasculature will be remodeled to their normal shape and size [7,8,9,10,11]
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