Bone anabolic therapy with selective prostaglandin analogs.
Prostaglandin E(2) has been shown to increase bone mass in animals and humans but it also has considerable dose limiting systemic side effects. The molecular description of multiple seven transmembrane domain G protein coupled prostanoid receptors offered the opportunity to probe the skeletal effects of specific receptors using selective agonists. Bone effects have been reported with many of the prostanoid receptors, with most interest focused on the anabolic effects of EP2, EP4, and FP receptors. Current data suggests activity at the EP2 receptor stimulates formation, activity at the EP4 receptor stimulates resorption (and possibly formation), and activity at the FP receptor produces new trabeculae. However, caution must be exercised in extending the effects of prostanoids in isolated systems to systemic skeletal effects, since tissue level effects are the cumulative result of bone formation and bone resorption. Furthermore, species differences in receptor sequence and density confound extrapolation of effects from one model to another model. While these molecular targets increase our insight into how the skeleton can be affected pharmacologically, they still do not answer questions about the role of naturally occurring prostaglandins in skeletal health. This manuscript will review some of the recent advances in knowledge of the bone anabolic effects of selective prostanoid ligands.
Hartke
J R
JR
Procter and Gamble Pharmaceuticals, Mason, OH 45040, USA. hartke.jr@pg.com
Lundy
M W
MW