Co-administration of antiresorptive and anabolic agents: a missed opportunity

Co-administration of antiresorptive and anabolic therapies has appeal because these treatments target the two main abnormalities in bone remodeling responsible for bone loss and microstructural deterioration. Antiresorptives reduce the number of basic multicellular units (BMUs) remodeling bone and reduce the volume of bone each BMU resorbs. Intermittent parathyroid hormone (PTH) increases the volume of bone formed by existing BMUs and those generated by PTH administration. PTH also increases bone formation by stimulating the differentiation, maturation, and longevity of osteoblast lineage cells residing upon quiescent bone surfaces. Despite these rationally targeted actions, enthusiasm for this approach waned when combined therapy blunted the increase in areal bone mineral density (aBMD) relative to that produced by PTH. Although many studies have since reported additive effects of combined therapy, whatever the aBMD result (blunting, additive, or null), these outcomes give little, if any, insight into changes in bone's material composition or microstructure and give misleading information concerning the net effects on bone strength. Combined therapy remains a potentially valuable approach to therapy. Because studies of antifracture efficacy comparing combined with single therapy are unlikely to be performed in humans, efforts should be directed toward improving methods of quantifying the net effects of combined therapy on bone's material composition, microarchitecture, and strength.