tetracycline and deoxypyridinoline

Estrogen replacement is currently the preferred therapy for postmenopausal osteoporosis, although its mechanism of action remains poorly understood. Its primary action on bone is generally considered to be antiresorptive, but there is evidence in animals to suggest a stimulatory effect on bone formation. We have now attempted to detect a similar effect in humans by administering hormone replacement therapy (estradiol valerate 2 mg/day and dydrogesterone 5 mg/day given in a continuous, combined manner) to ten postmenopausal women. We carried out histomorphometric analyses of transiliac bone biopsies after quadruple tetracycline labeling, which was commenced before and continued during the first 4 weeks of hormone replacement therapy. Biochemical markers of bone turnover suggested that bone resorption decreased, but no significant effects on histomorphometric parameters of bone formation were detected. We conclude that hormone replacement therapy at the dose given does not stimulate bone formation in the iliac crest as assessed by histomorphometry.

Topics: Absorptiometry, Photon; Amino Acids; Biomarkers; Bone Density; Bone Development; Drug Therapy, Combination; Dydrogesterone; Estradiol; Estrogen Replacement Therapy; Female; Femur Neck; Follicle Stimulating Hormone; Humans; Ilium; Lumbar Vertebrae; Luteinizing Hormone; Middle Aged; Osteoporosis, Postmenopausal; Tetracycline

The aim of this study was to evaluate the value of the urinary excretion of the pyridinium crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), as markers of bone resorption in the rat. The excretion of the crosslinks was compared with that of urinary [3H]tetracycline ([3H]TC) excretion from chronically [3H]TC-prelabeled animals, a technique established to monitor bone resorption in the rat. Bone resorption was modulated by Ca restriction, infusion of PTH, thyroparathyroidectomy, and administration of different bisphosphonates. Furthermore, the urinary crosslinks were assessed in three different osteopetrotic mutations in the rat. We found a delayed response of Pyr and D-Pyr excretion to acute changes in bone resorption compared with [3H]TC excretion. This delay was 1 day after Ca restriction and longer after other treatments, such as PTH administration or bisphosphonate treatment, with which it was more than 3 weeks. In contrast, chronic states with stimulation or inhibition of bone resorption showed similar changes in excretion of the urinary crosslinks and [3H]TC, except after PTH administration. The excretion of the crosslinks was greatly reduced in osteopetrotic rats (op/op, tl/tl, and ia/ia) and increased to normal levels in tl/tl rats after stimulation of bone resorption by M-CSF administration. These results suggest that, in rats, urinary excretion of the pyridinium crosslinks reflects bone resorption in chronic but not always in acute conditions. The cause of this discrepancy is still unclear.

Topics: Amino Acids; Animals; Biomarkers; Bone and Bones; Bone Resorption; Diphosphonates; Male; Osteopetrosis; Rats; Rats, Wistar; Tetracycline