Intermittently administered human parathyroid hormone(1-34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys

Cortical porosity in patients with hyperparathyroidism has raised the conce rn that intermittent parathyroid hormone (PTH) given to treat osteoporotic patients may weaken cortical bone by increasing its porosity. We hypothesiz ed that treatment of ovariectomized (OVX) cynomolgus monkeys for up to 18 m onths with recombinant human PTH(1-34) [hPTH(1-34)] LY333334 would signific antly increase porosity in the midshaft of the humerus but would not have a significant effect on the strength or stiffness of the humerus, We also hy pothesized that withdrawal of PTH for 6 months after a 12-month treatment p eriod would return porosity to control OVX values. OVX female cynomolgus mo nkeys were given once daily subcutaneous (sc) injections of recombinant hPT H(1-34) LY333334 at 1.0 mug/kg (PTH1), 5.0 mug/kg (PTH5), or 0.1 ml/kg per day of phosphate-buffered saline (OVX), Sham OVX animals (sham) were also g iven vehicle. After 12 months, PTH treatment was withdrawn from half of the monkeys in each treatment group (PTH1-W and PTH5-W), and they were treated for the remaining 6 months with vehicle. Double calcein labels were given before death at 18 months. After death, static and dynamic histomorphometri c measurements were made intracortically and on periosteal and endocortical surfaces of sections from the middiaphysis of the left humerus, Bone mecha nical properties were measured in the right humeral middiaphysis, PTH dose dependently increased intracortical porosity. However, the increased porosi ty did not have a significant detrimental effect on the mechanical properti es of the bone. Most porosity was concentrated near the endocortical surfac e where its mechanical effect is small. In PTH5 monkeys, cortical area (Ct, Ar) and cortical thickness (Ct,Th) increased because of a significantly inc reased endocortical mineralizing surface. After withdrawal of treatment, po rosity in PTH1-W animals declined to sham values, but porosity in PTH5-W an imals remained significantly elevated compared with OVX and sham, We conclu de that intermittently administered PTH(1-34) increases intracortical poros ity in a dose-dependent manner but does not reduce the strength or stiffnes s of cortical bone.