Bone-seeking labels as markers for bone turnover: validation of urinary excretion in rats

Summary Urinary excretion of tritiated tetracycline ( 3 H-TC) and 41 Ca tracers was validated as reflecting skeletal disappearance of these bone-seeking tracers as a direct measure of bone turnover following ovariectomy in rats. Introduction Tritiated tetracycline ( 3 H-TC) and Ca tracers have been used to measure bone resorption in animal models, but urinary excretion of these labels has not been directly compared to skeletal turnover. We aimed to evaluate the use of bone-seeking labels by comparing label release into urine with label in the skeleton when bone turnover was perturbed following ovariectomy. Methods Sixty-four 6-month-old ovariectomized (OVX) rats were randomized to one of eight groups in a 2 × 4 design that differed in time of 3 H-TC and 41 Ca administration following ovariectomy (1 month, when bone turnover would be accelerated following estrogen depletion or 3 months when bone loss due to OVX had slowed down) and time of euthanasia (1 week, 1 month, 3 months, and 6 months post-dose). Twenty-four-hour urine pools over two to four consecutive days and total skeleton were collected and recovered for the assessment of 3 H-TC and 41 Ca. Results Urinary 3 H-TC levels reflected skeletal 3 H-TC levels ( r = 0.93; p