Abstract
Sclerostin is a negative regulator of osteoblast differentiation and bone formation, probably through inhibition of the Wnt pathway. Distraction osteogenesis (DO) can be complicated by osteopenia and poor anabolic response, which may benefit from anabolic therapy. Sclerostin antibody (Scl-Ab) has been reported to stimulate bone formation and restore bone mass and strength in aged ovariectomised rats as well as to enhance fracture healing. We sought to examine the effects of Scl-Ab in a rat model of DO.
A femoral osteotomy was stabilised with an EBI fixator in male Sprague Dawley rats, with distraction of 0.25mm twice daily to a total 7mm. Saline or Scl-Ab was administered twice weekly throughout distraction and/or up to 4 or 6 weeks post-commencement of distraction. Three groups were examined, Saline, Delayed Scl-Ab (D Scl-Ab, post distraction only) and Continuous Scl-Ab (Cont Scl-Ab).
Radiographs demonstrated a trend for increased union rates with Scl-Ab at 6 weeks, with 50% of animals for D Scl-Ab or Cont Scl-Ab versus 20% of control animals. DEXA scans at 2 weeks revealed a 63% increase in regenerate BMD in the Cont Scl-Ab group (p< 0.01) and a 41% increase in the D Scl-Ab group (p< 0.05), compared to Saline. In addition, an increase of 116% in BMC was seen in the Cont Scl-Ab group (p< 0.01). At 6 weeks regenerate bone area was increased 18% in D Scl-Ab and 23% in Cont Scl-Ab. μCT scans of the regenerate revealed an 85%-89% increase in bone volume with Scl-Ab treatment at 6 weeks (p< 0.05). Bone volume ratio (BV/TV) was increased 77%-82% (p< 0.05).
Scl-Ab treatment enhanced the amount of bone formed in this distraction model, when given throughout or post-distraction. Histological assessment of dynamic bone formation parameters will reveal the mechanism behind the enhanced repair, and its mechanical consequences will be examined.
