A method for continual monitoring of bone resorption in rats: evidence for a diurnal rhythm

A method has been developed to monitor bone resorption (BR) based on the urinary excretion of [3H]tetracycline ([3H]TC) from chronically prelabeled rats. This is possible because the [3H]TC released from bone has been found to be in a form that is not or only poorly bound to apatite and thus not reincorporated into newly formed bone. When BR was increased by means of dietary calcium restriction, parathyroid hormone (PTH) infusion, or retinoid injections, urinary [3H]TC doubled. When BR was inhibited by feeding calcium supplements or administration of dichloromethylenebisphosphonate, [3H]TC excretion dropped by two-thirds. Thyroparathyroidectomy inhibited [3H]TC excretion by one-third. The results obtained with this technique are therefore similar to those obtained with other methods such as 45Ca kinetics. The effect of dietary manipulations on BR was detected within 6 h of changing diet. Furthermore, a strong diet-dependent but PTH- and calcitonin-independent diurnal rhythm in BR was found. By use of this technique, bone resorption can be assessed continuously over long periods, and the acute regulation of bone resorption can be studied for the first time.