Acute and Subacute Oral Toxicity Tests of Sintered Dicalcium Pyrophosphate on Ovariectomized Rats for Osteoporosis Treatment

Abstract

Sintered dicalcium pyrophosphate (SDCP) is a synthetic pyrophosphate analog that could be utilized in the treatment for osteoporosis. In this study, an ovariectomized rat model is used to evaluate the systematic toxicity of orally administered SDCP relative to its effects on bone mass. Ovariectomized Wistar rats were treated with experimental medication with different dosing strategies (0.5 mg/kg five days weekly, and 2.5 mg/kg once weekly) for once (acute oral toxicity test) and four weeks (subacute oral toxicity test) followed by recovery period. Clinical signs of toxicity, body weight, and food consumption of rats were recorded. Blood samples were collected for hematological and blood biochemical analyses. Rats were sacrificed for necropsy and major visceral organs were harvested for histological examination after the recovery period. Long bones of four limbs were harvested to evaluate the effects of SDCP on bone mass. Results showed that there was no change in clinical signs, body weight, food consumption, hematology, blood biochemistry, necropsy, and histological examination attributable to the oral administration with SDCP to rats during the dosing period and the recovery period. Analysis of bone ashes revealed that the ovariectomized rats ingested with 0.5 mg/kg SDCP five days weekly continually for four weeks increased bone mineral contents significantly. In the ovariec-169 Biomed. Eng. Appl. Basis Commun. 2010.22:169-176. Downloaded from www.worldscientific.com by NANYANG TECHNOLOGICAL UNIVERSITY on 08/26/15. For personal use only.tomized rats ingested with 2.5 mg/kg SDCP once weekly continually for four weeks, the bone mineral contents were increased to normal bone quality. This study indicates that the SDCP can increase bone mass in the ovariectomized rat with no deleterious effects.

Repair of Critical-Sized Mandible Defects in Aged Rat Using Hypoxia Preconditioned BMSCs with Up-regulation of Hif-1α

“…The processes of angiogenesis and osteogenesis are coupled during bone regeneration 39 . Blood vessels not only transport oxygen and nutrients but also play an important role in bone formation and remodeling by mediating the interaction between osteoblasts, osteocytes, osteoclasts, and vascular cells 40 . These data confirmed that hypoxia preconditioned BMSCs had a better angiogenic capacity in vitro .…”

Long-Term Oral Toxicity and Anti-osteoporotic Effect of Sintered Dicalcium Pyrophosphate in Rat Model of Postmenopausal Osteoporosis

“…SDCP, which can reduce bone resorption, should be useful for the treatment of osteoporosis [ 22 ]. Although previous acute and subacute oral toxicity studies have reported that the ingestion of SDCP did not show deleterious effects on test subjects [ 21 ], the long-term oral toxicity has not been tested. Regarding the potential toxic effects of SDCP, we found no clinical signs of toxicity and no changes in food consumption, hematology, or necropsy attributable to the oral administration of SDCP.…”

“…It was reported that elcatonin has an inhibitory effect on appetite, and a similar finding was also observed in rats treated with ALN [ 24 ]. Previous acute and subacute oral toxicity studies showed that rats treated with SDCP had a relatively lower weight than those of OVX rats [ 21 ], which reveals that SDCP may also inhibit appetite. In spite of the significant differences in body weight, there was no significant change in the femur volume, length, or width in the OVX + SDCP and OVX + ALN groups when compared with the OVX group.…”

“…Sections were stained with Goldner’s trichrome stain (Muto Pure Chemicals, Tokyo, Japan). The sections of distal femur metaphyses were used to evaluate the bony porosity, and the thickness and interconnections between trabeculations were evaluated as done in a previous study [ 21 ]. Five non-continuous sections were observed for each sample, and five rats were included to calculate the bony porosity for each group.…”

“…Previous acute and subacute oral toxicity studies have shown that the ingestion of SDCP did not have any deleterious effect on OXV rats. Furthermore, oral administration of SDCP can decrease bony porosity and increase bone mineral content [ 21 ]. The purpose of the present study was to further evaluate the long-term oral toxicity of SDCP and the effects of SDCP on bone turnover markers and bone mass in osteoporotic rats.…”