Bone histomorphometry and bone quality

Excerpt

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). …