The Effects Of Simvastatin On Bone Healing Around Titanium Implants In Osteoporosis Rats

Osteoporosis has been defined as a systemic skeletal disease characterized by gradual loss and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to substantial morbidity. Pathologic conditions causing bone loss such as hyperparathyroidism, hyperthyroidism, Cushing'disease, and glucocorticoid treatment can induce osteoporosis. However, the most common cause of osteoporosis is the decrease of estrogen during menopause or after ovariectomy. Significant relationships have been reported between oral bone and skeletal bone mass in postmenopausal women with osteoporosis. A few animal studies, using ovariectomiaed animal models, have demonstrated that estrogen deficiency could induce histologic changes around titanium screw dental implants. Osteoporosis could, therefore, be considered a risk factor in treatment planning and in determining the prognosis for patients considering dental implants. Most drugs currently available to treat osteoporosis are antiresorptive agents, including estrogen, bisphosphonates, and selective estrogen receptor modulators et al. To date, a bone anabolic drug available for oral administration is not available for the treatment of established osteoporosis. Recent studies have suggested that statins may exert antiresorptive and bone anabolic effects. The aim of this study was to evaluate the effect of Simvastatin on bone around titanium implants placed in rats and to investigate the effect of Simvastatin on bone metabolism in Osteoporosis rats. This study included two parts:Part one: Effects of Simvastatin on Bone Metabolism in Osteoporosis RatsMethods 54 female SD Rats aged 3 months were divided into three groups by randomized block design: Sham-operated groups (SHAM), ovariectomized group (OVX) and Simvastatin with ovariectomized rats group (OVX＋SIM). When osteoporosis model was established at 8 weeks, Simvastatin were administered orally 5mg.kg-1.d-1 to OVX＋SIM group and normal saline to the other two groups. The rats were sacrificed separately at 12th week and 20th week. Blood sample were collected to obtain serum levels of alkaline phosphatase (ALP), Ca, P, bone specific alkaline phosphatase (BALP), and bone gra protein (BGP) at the time of killing. Results The level of BALP was significantly increased in the OVX＋SIM group as compared with two other groups at 12 weeks (3.73±0.46, P＜0.01). At 20 weeks, the level of BGP in the OVX＋SIM group was significantly increased too (9.244±1.98, P＜0.01). Compared with 12 weeks, the levels of BALP were significantly decreased at 20 weeks in all groups (2.334±0.77, 1.504±0.34, 2.22±0.28, P＜0.05, P＜0.01), and the level of BGP of OVX group was significantly decreased too (4.024±0.72, P＜0.05). Conclusion Our results support a general beneficial effect of simvastatin on bone of Osteoporosis rats.Part two: The effects of Simvastatin on Bone Healing Around Titanium Implants in Osteoporosis RatsMethods The tibiae including dental implants were excised from the sacrificed rats and fixed with 10％neutral buffered formalin for 1 week. The specimens were dehydrated by ascending series of ethanol and then embedded in methyl methacrylate resin. Undecalcified sections approximately 50μm thick and longitudinal to the implant were obtained with Letize 1600 saw microtome and bone grinding slice technique. Finally, the sections were stained with 0.1％toliidine-blue and and methylene blue-basic fuchsin solution separately for light microscopy. Using these pictures, the bone contact ratio (BCR) and bone area (BA) within the limits of implant threads were obtained and arranged for cortical (zone A) and cancellous (zone B) bone regions and bone density (BD) of zone B in a 500μm -wide zone lateral to the implants were obtained too. Results For zone A, intergroup analysis showed that no significant differences regarding BCR and BA at 12 (implant placement 4 weeks) and 18 weeks (implant placement 12 weeks) were noted (P＞0.05). In contrast, in zone B, intergroup analysis showed that significant differences regarding BCR, BA, and BD were observed. Simvastatin positively affected BCR, BA, and BD in zone B, and both OVX＋SIM and SHAM groups demonstrated higher BCR, BA, and BD than OVX group (P＜0.01, P＜0.05). Conclusion Within the limits of the present study, it can be concluded that Osteoporosis can significantly influence bone healing in the cancellous bone around titanium implants inserted in rats and that Simvastatin can counter this harmful effect. Simvastatin may, therefore, have a role in improving the osseointegration of pure titanium implants in rats with Osteoporosis...