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

Abstract

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. 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. 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. Urinary (3)H-TC levels reflected skeletal (3)H-TC levels (r = 0.93; p < 0.0001) over a wide range of bone turnover rates in response to an intervention. Urinary (41)Ca and (3)H-TC excretion were highly correlated (r = 0.95, p < 0.0001). This study confirms that bone-seeking label excretion into the urine directly measures bone turnover.