Partial Restoration Of Skeletal Strength In Ovariectomized Rats By Treatment With Strontium Salts

AIM Ovariectomy of female rats induces significant bone-loss by depriving endogenous estrogen production. We assessed whether administration of strontium salts had a therapeutic benefit in this animal model of postmenopausal osteoporosis. INTRODUCTION In most women after menopause, the rate of bone loss exceeds the rate of bone formation, resulting in a net decrease in bone mass and ultimately in development of osteoporosis and elevated risk of sustaining fragility fracture. Most approved osteoporosis treatments work by decreasing the rate of bone resorption, however, these treatments also decrease new bone formation over time due to the coupling between these two processes. Elemental non-radioactive Strontium has been demonstrated to have both an anti resorptive as well as an anabolic effect on skeletal metabolism. This has been demonstrated in animal experiments after chromic administration of non-radioactive elemental strontium for up to two years. Our goal was to assess whether short term treatment with strontium in ovariectomized rats would affect biochemical markers of bone turnover as well as promote a bone strength. METHODS The study was performed in 48 female 5 months old Sprague-Dawley rats. After 4 weeks acclimatization, 12 rats were subjected to sham operation and the remaining 36 were ovariectomized (OVX). After 4 weeks, the 36 OVX rats were randomized into three groups and subjected to treatment by oral gavage with vehicle alone or vehicle + 533 mg/kg/day strontium glutamate (S-G) or 300 mg/kg/day strontium malonate (S-M)(both doses correspond to 137 mg ionic strontium/kg/day). The treatment period was five weeks, and at the end we analyzed circulating levels of calcium, strontium magnesium and iron and bone turnover by measuring the resorption marker CTX (RatLaps ELISA) and the formation marker osteocalcin (RatMID ELISA). Samples from week 4 and week 9 was measured and the response calculated as the post treatment value in percent of the pretreatment value. Bone strength was analyzed by indentation testing and BMD measurement by pQCT of femurs from the rats. RESULTS Strontium content at the end of the 5 week treatment period showed relatively large inter-individual variation with average levels in S-G treated animals of 76404606 ppm and 59641969 ppm. Calcium, magnesium and iron levels were not affected by the treatments (table 1). CTX decreased significantly compared to vehicle treatment over the five week treatment period in the S-M treated but not in the S-G treated rats. None of the treaments decreased bone formation. pQCT analysis of the distal femur revealed only a relatively modest effect of strontium treatment on BMD (693 and 703 mg/cm3 in S-M and S-G respectively compared to 671 mg/cm3 in vehicle treated OVX and 750 mg/cm3 SHAM rats). Bone strength analysis revealed a significant increase (p