Strontium–calcium coadministration stimulates bone matrix osteogenic factor expression and new bone formation in a large animal model

Abstract

Strontium (Sr) has become increasingly attractive for use in the prevention and treatment of osteoporosis by concomitantly inhibiting bone resorption and enhancing bone formation. Strontium shares similar chemical, physical, and biological characteristics with calcium (Ca), which has been widely used as a dietary supplement in osteoporosis. However, the effects of Sr-Ca coadministration on bone growth and remodeling are yet to be extensively reported. In this study, 18 ovariectomized goats were divided into four groups: three groups of five goats each treated with 100 mg/kg/day Ca, Ca plus 24 mg/kg/day Sr (Ca þ 24Sr), or Ca plus 40 mg/kg/day Sr (Ca þ 40Sr), and three untreated goats fed low calcium feed. Serum Sr levels increased 6-and 10-fold in the Ca þ 24Sr and Ca þ 40Sr groups, respectively. Similarly, Sr in the bone increased four-and sixfold in these two groups. Sr-Ca coadministration considerably increased bone mineral apposition rate (MAR). The expression of insulin-like growth factor (IGF)-1 and runt-related transcription factor 2 (Runx2) was significantly upregulated within the Ca þ 40Sr treatment group; tumor necrosis factor (TNF)-agr; expression was significantly downregulated in the Ca and Ca þ 40Sr groups. The results indicate that Sr-Ca coadministration increases osteogenic gene expression and stimulates new bone formation.

Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation

“…In addition, Ca sources such as coral sand increased RUNX2 and COL-1 mRNA expression [39]. Moreover, Sr-Ca co-administration upregulated RUNX2 mRNA expression [40]. These results provide important insights into how the downstream components of the BMP-2 signaling pathways, which we have identified as RUNX2 and receptor-activated SMADs and induce osteoblast differentiation in OVX rat (Figure 8).…”

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

“…This Sr compound exerts a beneficial effect in a goat osteoporosis model by preventing trabecular bone deterioration. 13,14 Both Veh and Sr compound were orally administrated by gavage daily for 12 weeks starting immediately postoperatively. The dosage exerts anabolic effect on bone in mice and rats.…”

A new insight into the dissociating effect of strontium on bone resorption and formation

“…The expression of insulin-like growth factor (IGF)-1 and runt-related transcription factor 2 (Runx2) was significantly up-regulated within the treated group; tumour necrosis factor expression was also significantly down-regulated in that group [22]. Small animal models (rats) have demonstrated that BMSCs produced larger osteogenic colonies but smaller adipogenic colonies in Sr-treated OVX rats.…”