BoneKEy Reports | BoneKEy Watch

Therapeutic potential of blocking DDK1 and sclerostin


Dickkopf-1 (DKK1) and sclerostin are both potent inhibitors of the Wnt signaling pathway and are known to have a crucial role in bone remodeling, bone formation and bone growth; expression of both Wnt inhibitors is known to decrease bone mass in humans and in animal models.

This review examines the evidence that specific monoclonal antibodies targeting these key inhibitors could have wide-ranging therapeutic potential. It incorporates studies investigating the effects of a specific anti-sclerostin monoclonal antibody (Scl-Ab), which was used in several animal models. The results revealed that Scl-Ab increased the rate of bone formation and led to greater bone strength and density. Scl-Ab used in models of bone repair also accelerated bone healing.

Evidence is also presented showing that a monoclonal antibody specific for DKK1 (DKK1-Ab) greatly enhanced bone formation in juvenile animals and also had positive effects in mature animals, who exhibited accelerated fracture healing. The authors note that the currently available evidence indicates that both DKK1-Ab and Scl-Ab could be developed further to treat osteoporosis and inflammatory bone diseases, to hasten fracture healing and to benefit multiple myeloma patients.

Editor's comment: The review highlights the clinical trials currently evaluating Scl-Ab and DKK1-Ab in patients for the treatment of bone loss and for fracture repair enhancement. Notably, effects of specific antibodies for these important Wnt antagonists in skeletal muscle or their role in potential muscle-bone interactions has not yet been explored.

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