Therapeutic Ion-Releasing Bioactive Glass Ionomer Cements with Improved Mechanical Strength and Radiopacity

Strontium ranelate is a newly developed drug that has been shown to significantly reduce the risk of vertebral and non-vertebral fractures, including those of the hip, in postmenopausal women with osteoporosis. In contrast to other available treatments for osteoporosis, strontium ranelate increases bone formation and decreases resorption. In this study, the dual mode of action of strontium ranelate in bone was tested in vitro, on primary murine osteoblasts and osteoclasts derived from calvaria and spleen cells, respectively. We show that strontium ranelate treatment, either continuously or during proliferation or differentiation phases of mouse calvaria cells, stimulates osteoblast formation. Indeed after 22 days of continuous treatment with strontium ranelate, the expression of the osteoblast markers ALP, BSP and OCN was increased, and was combined with an increase in bone nodule numbers. On the other hand, the number of mature osteoclasts strongly decreased after strontium ranelate treatment. Similarly to previous studies, we confirm that osteoclasts resorbing activity was also reduced but we found that strontium ranelate treatment was associated with a disruption of the osteoclast actin-containing sealing zone. Therefore, our in vitro assays performed on primary murine bone cells confirmed the dual action of strontium ranelate in vivo as an anabolic agent on bone remodeling. It stimulates bone formation through its positive action on osteoblast differentiation and function, and decreases osteoclast differentiation as well as function by disrupting actin cytoskeleton organization.

Bioglass 45S5 is an osteoproductive material, which resorbs by releasing its constitutive ions into solution. Treatment with the ionic products of Bioglass 45S5 dissolution in DMEM for 4 days increased human osteoblast proliferation to 155% of control. Two days after treatment, differential gene expression was analyzed by cDNA microarrays. Expression of a potent osteoblast mitogenic growth factor, insulin-like growth factor II (IGF-II), was increased to 290%. Additionally, there was a 168% increase in the concentration of unbound IGF-II protein in the conditioned media of treated osteoblasts. Expression levels of IGFBP-3, an IGF-II carrier protein, metalloproteinase-2 and cathepsin-D were also increased to 200, 340, and 310% of control levels, respectively. Metalloproteinase-2 and cathepsin-D are proteases that cleave IGF-II from its carrier proteins, resulting in the release of the unbound biologically active IGF-II. We suggest that the stimulatory effect of the ionic products of Bioglass 45S5 dissolution on osteoblast proliferation may be mediated by IGF-II. Copyright 2000 Academic Press.

Dental caries is a bacterially based disease. When it progresses, acid produced by bacterial action on dietary fermentable carbohydrates diffuses into the tooth and dissolves the carbonated hydroxyapatite mineral--a process called demineralization. Pathological factors including acidogenic bacteria (mutans streptococci and lactobacilli), salivary dysfunction, and dietary carbohydrates are related to caries progression. Protective factors--which include salivary calcium, phosphate and proteins, salivary flow, fluoride in saliva, and antibacterial components or agents--can balance, prevent or reverse dental caries. Caries progression or reversal is determined by the balance between protective and pathological factors. Fluoride, the key agent in battling caries, works primarily via topical mechanisms: inhibition of demineralization, enhancement of remineralization and inhibition of bacterial enzymes. Fluoride in drinking water and in fluoride-containing products reduces caries via these topical mechanisms. Antibacterial therapy must be used to combat a high bacterial challenge. For practical caries management and prevention or reversal of dental caries, the sum of the preventive factors must outweigh the pathological factors.