Hypercalcemia during the osteogenic phase after rat marrow ablation coincides with increased bone resorption assessed by the NTx marker

Marrow ablation is a model of bone turnover in which the excavated tibial i ntramedullary cavity is rapidly and reproducibly filled by osteoblasts with new woven bone (days 6-8), which is then rapidly resorbed by osteoclasts ( days 10-15), We showed previously (Magnuson et al,, 1997) that marrow ablat ion induces a-dramatic hypercalcemia and hypercalciuria in rats that unexpe ctedly peaked at the time of maximal osteogenesis and continued throughout the subsequent resorption phase, Based upon the amount of calcium mobilized and a peak of urinary hydroxyproline, we suggested that the hypercalcemia and hypercalciuria were due to increased systemic osteoclastic bone resorpt ion induced by marrow ablation, We now apply a new enzyme-linked immunosorb ent assay for rodent alpha(2)(I) N-telopeptide (NTx), a marker of bone reso rption, to the marrow ablation model to demonstrate that excretion of NTx p arallels that of calcium release in the operated control group, Specificall y, maximal NTx/ creatinine excretion coincides with the onset of hypercalce mia on days 7-8, A peak of NTx was also observed in methylprednisolone- and deflazacort-treated ablated animals. Analyses for urinary free deoxypyridi noline crosslink failed to detect a significant ablation-induced change in excretion. Interleukin 6 activity was increased in all operated control and glucocorticoid-treated groups after marrow ablation, whereas serum parathy roid hormone remained at presurgical levels in operated controls throughout . the 15-day study period. The NTx results confirm that bilateral tibial ma rrow ablation induces a burst of extratibial bone resorption and hypercalce mia 7-8 days later, We have estimated that the osteogenic phase of the abla tion model deposits 40 mg of calcium as hydroxyapatite crystals within the intramedullary cavity on days 6-8; this represents 33%-50% of the total blo od calcium content of a young rat. We hypothesize that the size and rapidit y of this demand for ionized calcium is met through an extratibial bone res orption pathway of osteoclast formation and activation that anticipates and fulfills this need, and that is initiated at the time of marrow ablation, (Bone 27:103-110; 2000) (C) 2000 by Elsevier Science Inc. All rights reserv ed.