Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway

Abstract

Aim: To evaluate the protective effects of strontium fructose 1,6-diphosphate (FDP-Sr), a novel strontium salt that combined fructose 1,6-diphosphate (FDP) with strontium, on bone in an ovariectomy-induced model of bone loss. Methods: Eighty female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Three months later, the rats were assigned to six groups (10 for each): sham-operated, OVX control, OVX+FDP-Sr (110, 220, or 440 mg/kg), or OVX+strontium ranelate (SR, 180 mg/kg). Drugs were administered orally for 3 months. When the treatment was terminated, the following parameters were assessed: bone mineral density (BMD), the biomechanical properties of the femur and lumbar vertebrae, trabecular histomorphology, serum phosphorus, calcium, bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRACP5b), N-telopeptide of type I collagen (NTx) and a series of markers for oxidative stress. Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) levels in serum were measured using ELISA and their gene expression levels in the bone were measured using R-T PCR. Results: Treatment with FDP-Sr (220 or 440 mg/kg) or SR (180 mg/kg) significantly increased the BMD and improved the bone microarchitecture and bone strength in OVX rats. The treatments also decreased in the levels of H 2 O 2 and MDA, restored the CAT level in serum and bone marrow, increased the serum B-ALP and decreased NTx and TRACP 5b in OVX rats. Treatment with FDP-Sr decreased the RANKL level, and increased the OPG level in serum in a dose-dependent manner. It also significantly down-regulated the RANKL expression and up-regulated OPG expression in bone marrow. Conclusion: FDP-Sr may be an effectve treatment for postmenopausal osteoporosis that acts, in part, via a decrease in osteoclastogenesis through the OPG\RANKL\RANK pathway.Keywords: osteoporosis; ovariectomy; strontium fructose 1,6-diphosphate; strontium ranelate; osteoprotegerin (OPG); receptor activator of NF-κB ligand (RANKL); bone mineral density; tartrate-resistant acid phosphatase 5 (TRACP5); N-telopeptide of type I collagen (NTx)

Liraglutide exerts a bone‑protective effect in ovariectomized rats with streptozotocin‑induced diabetes by inhibiting osteoclastogenesis

“…During osteoclastogenesis, RANKL drives osteoclast differentiation (20) while OPG antagonizes RANKL action (21), and the RANKL/OPG ratio determines osteoclastogenesis in the bone. Here, we showed that both STZ and OVX increased RANKL/OPG ratio, which is consistent with previous studies (30)(31)(32)(33). Liraglutide significantly reduced RANKL/OPG ratio compared to the untreated counterparts, indicating that liraglutide can inhibit osteoclastogenesis in STZ, OVX and STZ+OVX rats.…”

Metabolomic Profiles Delineate Signature Metabolic Shifts during Estrogen Deficiency-Induced Bone Loss in Rat by GC-TOF/MS

“…B-ALP and NTx of rats in OVX group significantly increased since the 12 th week (P<0.05) and 9 th week (P<0.05) post operation, respectively, compared with those in Sham group(shown in Figure 1A and 1B). The results indicated that OVX rat had the characteristic of bone high turnover rate according to the previous reports [29], [30].…”

“…BMD of the lumbar vertebrae (L1–L5) and left femur from anesthetized rats was measured (isoflurane) by dual-energy X-ray absorptiometry (GE, Lunar ProdigyTM) at the 12 th 24 th week post-operation. BMD was calculated by dividing the measured area by the bone mineral content (BMC), as previously reported [30]. Baseline of BMD was determined 1 week before surgery.…”

Histological study of the femur and the lumbar vertebrae in ovariectomized adult albino rats following administration of collagen hydrosylate

“…Similarly, several researchers clarified a significant increase in CTX after OVX [29]. Similarly, several researchers clarified a significant increase in CTX after OVX [29].…”