The Effects of Parathyroid Hormone (PTH) and PTHRelated Peptide on Osteoclast Resorption of Bone Slicesin Vitro: An Analysis of Pit Size and the Resorption Focus*

Abstract

The mechanism whereby PTH, a potent stimulator of bone resorption, may under certain circumstances exert anabolic effects on bone is not known, but it is possible that it involves reduction of the size of osteoclast resorption lacunae. We have therefore made a detailed in vitro study of the effects of PTH and PTH-related peptide (PTHrP) on resorption by neonatal rat osteoclasts paying particular attention to the plan area of resorption pits. In order to distinguish between increased resorption at a particular site and increased numbers of sites, we have used an eyepiece graticule to define a focus of resorption, namely an area occupying 1/116th of the bone slice, which may contain either one or several pits. In addition we have studied the relationship between the number of pits in a resorption focus and the total area of bone resorbed at the focus. We found that PTH and PTHrP, at doses between 2 x 10(-10) M and 2 x 10(-8) M, while exerting significant stimulatory effects on bone resorption, caused a reduction in the median plan area of pits. An increase in the number of resorption foci was the primary stimulatory effect of PTH and PTHrP, occurring within 6 h in the case of PTH. However, the plan area of bone resorbed at a focus showed no significant increase, despite an increase in the number of pits per focus, because as more pits were formed at a focus, the pits were smaller, thus partially dissipating the stimulatory effect of PTH on resorption. These results are consistent with the activation of new remodeling sites by PTH in vivo. Furthermore, the formation of smaller pits under the resorptive influence of PTH may, together with the maintenance of coupling between formation and resorption, play a role in the preservation of cancellous bone recorded in cases of primary hyperparathyroidism and the anabolic effect of exogenous PTH.