Significance Only recently have multiple, anabolic, bone-forming agents become available, raising the possibility that osteoporosis might be more effectively treated by combinatorial or sequential treatments rather than single agents. The discovery of osteolectin raised two important questions in this regard. First, what is the epistatic relationship between these agents? Second, would osteolectin have additive effects if combined with another agent? Our discovery that osteolectin mediates part of the effect of parathyroid hormone (PTH) on bone formation identifies a new mechanism by which PTH acts. The observation that PTH and osteolectin have additive effects provides proof-of-principle that combinatorial use can increase osteogenesis.