Abstract
Urinary excretion of bone labels can be used to monitor bone resorption. Here we investigate the effects of dosing frequency on label incorporation of various sites when bone turnover was perturbed by ovariectomy. We compared tritiated tetracycline (3H-TC) and 45Ca in two studies. Nine-month-old rats were given single or multiple injections of 3H-TC and 45Ca and sacrificed after 7 or 14 days. Six-month-old OVX rats were given 3H-TC and 41Ca tracers 1 or 3 months following ovariectomy (OVX + 1 mo or OVX + 3 mo, when bone turnover was higher or lower, respectively) and sacrificed 1 week, 1 month, 3 months, or 6 months postdose. Twenty-four-hour urine pools over 2–4 consecutive days as well as the proximal tibia, femur midshaft, lumbar vertebrae (L1–L4), and remaining skeleton were analyzed for 3H, 45Ca, and calcium content. Bone turnover as assessed by urinary 3H-TC was greater in OVX + 1 mo compared to OVX + 3 mo rats up to 6 months postdose. 45Ca labeling efficiency (% dose/g Ca) was significantly higher than for 3H and labeling was higher in trabecular-rich than cortical-rich bone. This study affirms that a single administration of either 3H-TC or 45Ca is a useful approach to measuring bone turnover directly. The amount of label incorporation into bone was greater in bone sites that were more metabolically active and in all sites when closer vs farther from OVX.
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References
Mühlbauer RC, Fleisch H (1990) A method for continual monitoring of bone resorption in rats: evidence for a diurnal rhythm. Am J Physiol 259:R679–R689
Talbott SM, Chowdhury H, Shapses SA (1999) Urinary 3H-Tetracycline and pyridinium crosslinks differ in their response to calcium restriction in mature and aged rats. Calcif Tiss Int 64:352–356
Cheong JMK, Gunaratna NS, McCabe GP, Weaver CM (2005) Use of 3H-tetracycline to assess the effects of ovariectomy stabilization and diet on bone resorption in rats. J Bone Miner Res 20(1):S192
Elmore D, Bhattacharyya MH, Sacco-Gibson N, Peterson DP (1990) 41Ca as a long-term biological tracer for bone resorption. Nucl Instrum Methods Phys Res B 52:531–535
Fitzgerald RL, Hillegonds DJ, Burton DW, Griffin TL, Mullaney S, Vogel JS, Deftos LJ, Herold DA (2005) 41Ca and accelerator mass spectrometry to monitor calcium metabolism in end stage renal disease patients. Clin Chem 51:2095–2102
Jackson GS, Weaver C, Elmore D (2001) Use of accelerator mass spectrometry for studies in nutrition. Nutr Res Rev 14:317–334
RodrõÂguez Barquero L, Los Arcos JM (1996) 41Ca standardization by the CIEMAT/NIST LSC method. Nucl Instrum Methods Phys Res A 369:353–358
Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191
Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951
Kutner MH, Nachtsheim CJ, Neter J, Li W (2005) Simultaneous inferences and other topics in regression. In: Kutner M, Nachtsheim C, Neter J, Li W (eds) Applied linear statistical models. McGraw-Hill, Boston, pp 168–170
Casella G, Berger RL (2002) Properties of a random sample: In: Statistical inference. Duxbury/Thomson Learning, Pacific Grove, CA, pp 240–245
DeMoss DL, Wright GL (1997) Analysis of whole skeleton 3H-tetracycline loss as a measure of bone resorption in maturing rats. Calcif Tissue Int 61(5):412–417
Cheong JMK, Martin BR, Jackson GS, Elmore D, McCabe GP, Nolan JR, Barnes S, Peacock M, Weaver CM (2007) Soy isoflavones do not affect bone resorption in postmenopausal women: a dose response study using a novel approach with 41Ca. J Clin Endocrinol Metab 92:577–585
Denk E, Hillegonds ED, Hurrell RF, Vogel J, Fattinger K, Hauselmann HJ, Kraenzlin M, Walczyk T (2007) Evaluation of 41Calcium as a new approach to assess changes in bone metabolism: effect of a biophosphonate intervention in postmenopausal women with low bone mass. J Bone Miner Res 22:1518–1525
Sandhu HS, Tonna EA (1986) Incorporation and stabilization of 3H-tetracycline in embryonic chick bone: an autoradiographic study. Acta Anat 127:133–136
Acknowledgments
We thank Dr. Alan York (Purdue University) for supplying dermastid beetles, Dr. Berdine Martin (Purdue University) for obtaining approval from PACUC, and Ania Kempa-Steczko, Pamela Lachcik, Mary Larimore, Doug Maish, and Jane Einstein for their technical assistance. This project was supported by the NIH Office of Dietary Supplements and NCCAM Project P50 AT00477.
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Cheong, J.M.K., Gunaratna, N.S., McCabe, G.P. et al. Bone Seeking Labels as Markers for Bone Turnover: Effect of Dosing Schedule on Labeling Various Bone Sites in Rats. Calcif Tissue Int 85, 444–450 (2009). https://doi.org/10.1007/s00223-009-9285-z
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DOI: https://doi.org/10.1007/s00223-009-9285-z