Several decades ago, a clinical condition that included severe bone overgrowth 
was described in a few patients in South Africa. The autosomal-recessive disease 
that later was named sclerosteosis was found to be caused by a mutation in the 
SOTS gene causing a lack of the protein sclerostin. This protein is produced by 
osteocytes and exerts its effect as an inhibitor of bone formation by blocking 
the Wnt signaling pathway. By the use of a monoclonal antibody that can block 
sclerostin a novel therapeutic pathway for rebuilding bone has been described. 
Preclinical studies have shown increased bone mass following subcutaneously 
administered anti-sclerostin antibody in animals with induced postmenopausal 
osteoporosis as well as in intact male rats and non-human primates. In a phase 
II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, 
has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg 
was given subcutaneously monthly or every three months and compared to 70 mg of 
oral alendronate given once a week or 20 μg of teriparatide subcutaneously once 
daily. All dose levels of romosozumab were associated with significant increase 
in BMD with the most pronounced gain in the group receiving 210 mg where lumbar 
spine BMD increased with 11.3% from baseline. The BMD for the placebo group 
decreased by 0.1% while the alendronate group increased 4.1% and the 
teriparatide increased 7.1%. Biochemical markers revealed a transitory increase 
in the bone formation marker P1NP while no change in the bone resorption marker 
β-CTX. In comparison, teriparatide resulted in an increase for both P1NP and 
β-CTX for the complete study period. Even though the rapid gain in BMD is 
promising when considering a treatment option for osteoporosis and other 
conditions with bone loss, there are so far no published studies on whether 
anti-sclerostin can reduce the number of fractures. Wnt signaling might also 
play an important role in fracture healing with substances that causes an 
upregulation of the Wnt pathway producing enhancement of the fracture healing 
process. Healing of experimental fractures in various animal models have shown 
improvement following subcutaneously administered anti-sclerostin antibody. 
While there are no published reports on the potential effect of systemically 
administered anti-sclerostin antibodies on fracture healing in humans.