Intermittent PTH acts predominantly by increasing remodeling - the number and activity of bone multicellular units (BMUs) – with some effect on modeling. It acts on committed osteoblast precursors to promote their differentiation, inhibit osteoblast and osteocyte apoptosis and inhibit the production of the bone formation inhibitor, sclerostin. PTH treatment also transiently activates osteoclasts, that might in turn produce activities enhancing osteoblast differentiation. Although PTHrP was discovered as a cancer product causing hypercalcemia, it is a paracrine/autocrine regulator in many tissues, including bone. Its aminoterminal structural similarity to PTH explains their shared action on the common receptor PTHR1. Genetic studies in mice reveal that osteoblast lineage-derived PTHrP is a crucial autocrine/paracrine regulator of bone remodelling, its deficiency resulting in an inadequate amount of bone. Post-natally PTH does not function physiologically to promote bone formation, but rather is a regulator of calcium homeostasis. Anabolic PTH mimics the local physiological action of PTHrP. PTHrP is so susceptible to proteolytic breakdown that it cannot be studied pharmacologically. Shorter PTHrP peptides have been used, with PTHrP(1-36) having an anabolic action at much higher doses than PTH(1—34), and claimed to have a lesser effect on resorption. Similar claims are made with a substituted analogue, Abaloparatide. The developing concept of a purely anabolic action though PTHR1 is questionable though, since resorption is an essential part of the bone remodeling sequence. The pharmacological challenge comes from the fact that physiologically, locally generated PTHrP operates at any one time only at those BMU’s that require it, whereas systemic administration of PTH (or of analogs) results in widespread BMU activation, with the inevitable outcome of readily measurable resorption activation.