A Pre-Clinical Assessment of Lithium to Enhance Fracture Healing in Healthy and Impaired Bone Rat Model

Fracture healing is a complex biologic process that fails in 5-10% of cases. There is a critical need for an adjunct treatment that can enhance fracture healing, particularly in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been reported to improve fracture healing via the canonical Wnt pathway. Recently, a pre-clinical study in our laboratory utilized a design of experiments approach to optimize the lithium administration parameters, resulting in improved strength (~46%) of healing femurs in otherwise healthy rats. In this thesis, the optimized lithium regimen was verified in healthy rats (~44% improvement). This regimen did not significantly impact healing of simple or comminuted fractures in osteoporotic rats. The lithium onset time may need to be extended to better target and enhance osteogenic activity in fractured osteoporotic bones. This thesis supports clinical evaluation of lithium for healthy long-bone fractures and will guide pre-clinical lithium optimization in impaired bones.

Year	Entry
1998	Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. October 1998;355(suppl):S7-S21.
2013	Bernick JH. A Preclinical Assessment of Lithium to Enhance Fracture Healing [Master's thesis]. University of Toronto; 2013.
2006	Reginster J-Y, Burlet N. Osteoporosis: a still increasing prevalence. Bone. February 2006;38(2)(suppl 1):4-9.
2009	Morgan EF, Mason ZD, Chien KB, Pfeiffer AJ, Barnes GL, Einhorn TA, Gerstenfeld LC. Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone. February 2009;44(2):335-344.
2003	Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. NEJM. September 25, 2003;349(13):1207-1215.
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Year

Entry

1998

Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. October 1998;355(suppl):S7-S21.

2013

Bernick JH. A Preclinical Assessment of Lithium to Enhance Fracture Healing [Master's thesis]. University of Toronto; 2013.

2006

Reginster J-Y, Burlet N. Osteoporosis: a still increasing prevalence. Bone. February 2006;38(2)(suppl 1):4-9.

2009

Morgan EF, Mason ZD, Chien KB, Pfeiffer AJ, Barnes GL, Einhorn TA, Gerstenfeld LC. Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone. February 2009;44(2):335-344.

2003

Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. NEJM. September 25, 2003;349(13):1207-1215.