Long-term bone response to a bioactive drug molecules in the femoral neck of osteoporotic rats
| Author | Affiliation |
|---|---|
Raina, Deepak Bushan | Deparment of Orthopedics, Skåne University Hospital, Lund University, Sweden |
Tägil, Magnus | Deparment of Orthopedics, Skåne University Hospital, Lund University, Sweden |
Lidgren, Lars | Deparment of Orthopedics, Skåne University Hospital, Lund University, Sweden |
| Date |
|---|
2021-05-27 |
Orthopedics, Physiology and Sports Medicine
Fragility fractures are common among the elderly. Zoledronic acid (ZA) is a potent bisphosphonate used clinically with documented positive preventive effect on fragility fractures. Systemic use of ZA has shown positive results, furthermore, studies indicated local usage of low-dose ZA, leads to improved bone formation. We aimed to evaluate the long-term effects of local ZA and rhBMP-2 delivery on bone remodeling in the femoral neck canal of osteoporotic rats. In ovariectomized rats femoral neck canals holes were drilled and defects were treated as follows: G1) empty (n=8), G2) Calcium sulphate(CaS)/hydroxyapatite(HA) biomaterial (n=8), G3) CaS/HA biomaterial+systemic ZA (n=11), G4) CaS/HA+Local ZA(10 μg) (n=11), G5) CaS/HA+Local ZA(10 μg)+rhBMP-2(5 μg) (n=9). To establish that the CaS/HA biomaterial is an optimal carrier for local ZA delivery, we used 14C-ZA to study the bioavailability of ZA during the entire course of bone regeneration and compare it to the ZA available in the femoral neck canal when ZA was delivered systemically (s.c injection). Animals were sacrificed after 24-weeks and both legs were subjected to micro-CT imaging, then the specimens that received 14C-ZA were subjected to scintillation counting while the rest of the specimens were tested mechanically to evaluate the peak force to fracture of the femoral neck. Significantly higher bone volume/tissue volume was observed in G4-G5 compared to G1-G3, indicating that local delivery of ZA or ZA+rhBMP-2 is necessary for bone regeneration. Scintillation counting results indicated similar amount of 14C-ZA accumulation in both legs in G3. In the local treatment group (G4), higher amount of 14C-ZA was observed in the defect leg. The results indicate that local delivery of ZA via the CaS/HA biomaterial carrier can aid in regeneration of large volumes bone within the femoral neck. This method could potentially be used in poor quality bone where hardwa[...].