Calculating clinically relevant drug doses to use in animal studies

Abstract

Dear Editor, We thank Dr. Pierre J. Marie for his interest in our recent study demonstrating that strontium ranelate (SrR) does not stimulate bone formation in ovariectomized (OVX) rats [1], and we appreciate this opportunity to respond. SrR has been found to be effective in reducing nonvertebral [2, 3] and vertebral [3–5] fractures in postmenopausal women. It has been proposed that SrR acts as a dual-acting agent with both antiresorptive and anabolic actions; however, whether it does both remains unclear. Our study was designed to address this issue. Dr. Marie raises an important point regarding the clinical relevance of the SrR doses used in our animal study (25 and 150 mg/kg). There is no universally accepted means of establishing clinical dose equivalency when exploring the effects of pharmaceutical agents in animal models. One common approach is to normalize drug dose by body mass (i.e., on a milligrams per kilogram basis). Based on this, the 25-mg/kg SrR dose we used is comparable to the 2-g/day dose in postmenopausal women (equates to 29–40 mg/day for 50–70 kg body mass). Clinically equivalent doses can also be calculated based on metabolic dose using the Osteoporos Int (2008) 19:1815–1817 DOI 10.1007/s00198-008-0741-9