Influence of bisphosphonate treatment on bone substitute performance in osteoporotic conditions

Abstract

Objective: Considering the elevated number of osteoporotic patients in need of bone graft procedures, we here evaluated the effect of alendronate (ALN) treatment on the regeneration of bone defects in osteoporotic rats. Bone formation was histologically and histomorphometrically assessed in rat femoral condyle bone defects filled with bone graft (Bio-Oss ® ) or left empty.Methods: Male Wistar rats were induced osteoporotic through orchidectomy (ORX) and SHAM-operated. The animals were divided into three groups: osteoporotic (ORX), osteoporotic treated with ALN (ORX + ALN) and healthy (SHAM). Six weeks after ORX or SHAM surgeries, bone defects were created bilaterally in femoral condyles; one defect was filled with Bio-Oss ® and the other one left empty. Bone regeneration within the defects was analyzed by histology and histomorphometry after 4 and 12 weeks.Results: Histological samples showed new bone surrounding Bio-Oss ® particles from week 4 onward in all three groups. At week 12, the data further showed that ALN treatment of osteoporotic animals enhanced bone formation to a 10-fold increase compared to non-treated osteoporotic control. Bio-Oss ® filling of the defects promoted bone formation at both implantation periods compared to empty controls. Conclusion:Our histological and histomorphometric results demonstrate that the enteral administration of alendronate under osteoporotic bone conditions leverages bone defect regeneration to a level comparable to that in healthy bone. Additionally, Bio-Oss ® is an effective bone substitute, increasing bone formation, and acting as an osteoconductive scaffold guiding bone growth in both healthy and osteoporotic bone conditions.Significance: Based on the results of this study, enteral use of ALN mitigates adverse effects of an osteoporotic condition on bone defect regeneration.

Injectable and high-strength PLGA/CPC loaded ALN/MgO bone cement for bone regeneration by facilitating osteogenesis and inhibiting osteoclastogenesis in osteoporotic bone defects

“…During the process of cement injection into the defect area, it was observed that the anti-washout property maintained the shape of the cement from being flushed away by blood. ALN is one of the most commonly used anti-osteoporosis drugs, which can effectively inhibit bone resorption of osteoclasts and reduce osteolysis, has been widely used in clinical practice in recent years [ [40] , [41] , [42] ]. Studies have reported that implemented local ALN delivery to promote bone repair by loading ALN on injectable hydrogels could effectively promote bone regeneration in osteoporotic rats in vivo [ 42 , 43 ].…”

“…ALN is one of the most commonly used anti-osteoporosis drugs, which can effectively inhibit bone resorption of osteoclasts and reduce osteolysis, has been widely used in clinical practice in recent years [ [40] , [41] , [42] ]. Studies have reported that implemented local ALN delivery to promote bone repair by loading ALN on injectable hydrogels could effectively promote bone regeneration in osteoporotic rats in vivo [ 42 , 43 ]. It is also confirmed that loading ALN in a dual-delivery system with substance P could effectively regulate osteogenesis-osteoclastogenesis balance for promoting immediate implant osseointegration [ 44 ].…”