Session IX - Basic Science
The Effect of Levodopa or Levodopa-Carbidopa (Sinemet®) on Fracture Healing
Purpose: Fracture nonunions represent a significant musculoskeletal problem. Some treatments to improve the healing process have focused on Levodopa (L-dopa), which is used in the treatment of Parkinson's disease. This drug is converted in the body into dopamine, which stimulates the anterior hypophysis of the pituitary gland to secrete growth hormone (a secretagogue). The purpose of this study was to determine the effectiveness of L-dopa and L/carbi-dopa (L-dopa/carbidopa, trademarked as Sinemet®) in stimulating fracture healing.
Methods: Under isoflurane anesthesia, the right femurs of 42 Sprague-Dawley female retired breeder rats were exposed, stripped of their periosteum, and fractured in the middle of the diaphysis by notching the bone with a miniature file until it could be snapped by hand. An intramedullary omega pin was inserted into the gap to hold the two bone segments approximately 2 mm apart. One group was administered 0.2g/kg/day of L-dopa, the second group 0.2/0.02g/kg/day of L/carbi-dopa in their powdered rat chow, and the Sham group received plain powdered rat chow. At week 5, the femurs were excised and radiographed. Energy to failure, maximum load displacement, ultimate load, and flexural rigidity were determined by 3 point bending tests using an Instron 8500 for material testing. Student's t test was used to compare the groups statistically.
Results: Although the amount of food consumed by the three groups was not statistically different, the L/carbi-dopa group lost significant weight (P<0.05) when compared to the L-dopa and Sham rats. At 5 weeks after fracture, the femurs of 3 of 10 (30%) Sham rats healed, compared to 7 of 14 (50%) L/carbi-dopa and 10 of 12 (83%) L-dopa-treated femurs. The healed L-dopa rat femurs had significantly (P=0.007) greater energy to failure (38.6mJ±3.7) than the healed Sham rats (15.9mJ±5.8); the L-dopa femurs' ultimate load of 38.2N±5.2 approached statistical significance as compared to the Sham femurs' ultimate load of 19.8N±4.8 (P=0.061).
Conclusion/Significance: The results of this study confirm the effectiveness of L-dopa in stimulating healing of rat femurs both qualitatively and quantitatively. Because L-dopa is currently only marketed in combination with carbidopa, it would be beneficial if a pharmaceutical company would remarket L-dopa alone.