Although PTH(1–34) and PTH are now approved as anabolic therapies for osteoporosis, much remains to be learned about their mechanisms of action and how they interact with antiresorptive agents. In 1995, Pierre Delmas and his colleagues published a landmark paper [1] in which histomorphometric analysis was used to explore the effects of combined treatment with an antiresorptive agent, the bisphosphonate tiludronate, and an anabolic agent, PTH(1– 34). They used 7-year-old female ewes, an animal model that faithfully mimics the slow bone remodeling activity seen in elderly women. The animals were divided into four groups. A control group received daily injections of saline. One group received daily injections of 500 IU of hPTH(1– 34), while another group was given 1 mg/kg per day tiludronate, also by subcutaneous injection. The fourth group received a combination of PTH(1–34) and tiludronate. A paired design was used in which iliac crest biopsies were collected before and after 90 days of treatment. The histomorphometric results were striking and, at that time, unexpected. PTH treatment increased parameters of bone resorption and formation with a sevenfold increase in tetracycline-labeled, bone-forming surface. In contrast, tiludronate treatment decreased resorption and formation parameters. Resorption indices were also decreased in the PTH+tiludronate group, while formation was either unchanged or decreased, depending on the individual parameter. The bottom line was that remodeling activation frequency was increased in the PTH group and decreased in both the tiludronate and the PTH+tiludronate groups and, as a result, the coadministration of a bisphosphonate had completely abolished the anabolic action of PTH. The histomorphometric data were mirrored by parallel changes in biochemical markers of resorption (pyridinoline and hydroxyproline) and formation (osteocalcin and alkaline phosphatase). This paper shed important light on the mechanism of action of PTH and how it interacts with bisphosphonates. The authors posited that, inasmuch as bisphosphonates have little, if any, effect on osteoblasts, the failure to respond to PTH indicated that an increase in remodeling activation was a prerequisite for the complete anabolic response. By applying histomorphometry to an appropriate animal model, Delmas and colleagues were able to accurately predict (and explain) the outcome of the PaTH trial [2], published 7 years later. Earlier this year, Delmas and his team extended this observation to a clinical setting by observing the effects of PTH treatment in a patient with pycnodysostosis [3]. Pycnodysostosis is an extremely rare autosomal recessive bone disease caused by an inactivating mutation of cathepsin K, the major proteolytic enzyme in the osteoclast, leading to osteosclerosis. Iliac crest bone biopsies from this pycnodysostotic patient before and after 6 months of treatment with 20 μ/day of PTH(1–34) showed a complete lack of response to the treatment, again supporting the concept that some feature(s) of the osteoclast phenotype is essential for the anabolic effect of PTH. These two papers serve to illustrate a large body of work in which Professor Delmas has used the technique of Osteoporos Int (2009) 20 (Suppl 3):S243–S244 DOI 10.1007/s00198-008-0702-3