Methodology developed for the simultaneous measurement of bone formation and bone resorption in rats based on the pharmacokinetics of fluoride.
This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.
Bone Biology Laboratory, School of Medicine, Rosario National University, Santa Fe 3100, Rosario, Santa Fe, Argentina, maela_lupo@hotmail.com.
Maela
M
Lupo
Maria Lorena
ML
Brance
Brenda Lorena
BL
Fina
Lucas Ricardo
LR
Brun
Alfredo
A
Rigalli
D000469:Alkaline Phosphatase / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D016723:Bone Remodeling; D001862:Bone Resorption; D001842:Bone and Bones / Q000201:enzymology; D002118:Calcium / Q000737:chemistry; D005260:Female; D005459:Fluorides / Q000737:chemistry / Q000493:pharmacokinetics*; D007477:Ions; D008962:Models, Theoretical; D010012:Osteogenesis; D010052:Ovariectomy; D011237:Predictive Value of Tests; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D007477:Ions; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D005459:Fluorides; D002118:Calcium