Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model

Abstract

ObjectivesThe objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement.Materials and methodsEighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro‐CT, mechanical pull‐out test, histology, and bone serum markers.ResultsPeri‐implant micro‐CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri‐implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull‐out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant.ConclusionThe hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

Improvement of Osseointegration by Ultraviolet and/or Simvastatin Treatment on Titanium Implants with or without Bone Graft Materials

“…Possible molecular mechanisms of statins related to bone remodeling reported in the literature are various and complex [35,[40][41][42][43]. Simvastatin is the most investigated statin and has been proven to be a potent agent for improving implant fixation [43][44][45]. However, most statins are degraded when administered orally due to the extensive first-pass effect in the liver, and less than 5% of the drug is available to the general circulation, with even lower amounts available to the bones [44,46].…”

Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease

“…The non-surgical approach involves the usage of treatment such as physiotherapy, kinesitherapy, weight control, drugs. The main drugs used are hormones (parathyroid hormones, calcitonin, leptin), which act as regulating molecular pathways of cartilage metabolism; bisphosphonates (zoledronic acid, alendronate) which act as improving bone metabolism, reducing bone reabsorption; monoclonal antibodies (bevacizumab, adalimumab,) which act on articular cartilage promoting collagen production; statins (atorvastatin, which reduces cartilage degradation); supplements (glucosamine, chondroitin sulfate, vitamin C, vitamin D, Selenium, Zinc, Magnesium), which act as a cartilage nourishment [ 41 , 42 ]. In view of this, research has been conducted on regenerative alternatives to treat OA in an attempt to ease pain and diminish symptoms by regenerating tissue and maintaining stability in local cells.…”

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

“…The release of drugs that promote bone regeneration and osseointegration will make bone aggregate, adhere, and regenerate on the surface of the titanium implant. The process of osseointegration is enhanced by the action of drugs [ 107 ]; at the same time, with the gradual formation of bone trabeculae, tissue vascularization, the increase in the number of bone cells that grow in the titanium alloy pores, and bone mineralization, the development of the bone microenvironment around the drug-loaded titanium implant is inevitable. Significant changes will have a certain impact on the process of drugs’ release, diffusion, and absorption into the blood [ 108 ].…”