THE EFFECT OF MONOBUTYRIN ON FRACTURE HEALING IN AN OVARECTOMISED RODENT MODEL

Abstract

Introduction: Monobutyrin (MB) has been shown to be a potent angiogenic factor for adipose tissue. It is one of the many compounds secreted from adipocytes adding to the knowledge that adipose tissue is not merely a storage unit but has an endocrine function. Adipocytes and osteoblasts share a common precursor. In osteoporosis the proportion of fat in bone increases. As both are present at a fracture site the addition of MB may enhance fracture healing by stimulating angiogenesis.

Method: 138 Sprague Dawley rodents were ovarect-omised at 12 weeks of age. After a further 24 weeks each animal underwent a right closed femoral fracture stabilized with a retrograde k-wire using a standard model (Walsh et al. 1997). Animals were randomised into control (empty or substrate only) or MB of varying concentrations (2.5μg, 7.5μg, 25μg, 75μg). A percutaneous injection of 0.2mls of each of the above was then injected into the fracture site. Animals were culled at 1, 3 and 6 week time points post surgery. The right and left femurs were dissected out and analyzed using radiographic, mechanical testing, micro computed tomography and histology endpoints. Statistical analysis was perfomed with SPSS for windows.

Results: All animals recovered well from the procedure and no adverse reactions were noted following the addition of MB. A progression to union was seen with time in all groups. Mechanical testing did not result in a statistical difference between groups, however the trend showed improved healing in the 7.5μg Monobutyrin group. Radiographic grading again showed no statistical difference however, interestingly micro CT data showed an increasing trend in both trabecular number and bone surface area to volume with increasing concentrations of MB.

The histology results implied a potential acceleration in the early stage of fracture healing in the high dose (75 μg) MB group. However progression to union following this initial early phase acceleration was delayed as callus volume increased rather than union according to micro CT and histological data.

Discussion: The ability to augment fracture healing has significant clinical implications considering the “greying of society”. This study investigated the possibility of improving fracture healing by incorporating the angiogenic factor, Monobutyrin in an estrogen deficient animal model. Although the results do not conclusively demonstrate an improvement in fracture healing, they do imply that MB does affect the early phase of fracture healing in the estrogen deficient model. This study is limited in that the effects of MB on fracture healing in a non-estrogen deficient model was not considered. The ideal release kinetics for Monobutyrin as well as other factors remains unknown.