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Semaphorin 4d (Sema4d) has been proposed as a novel target gene for the treatment of osteoporosis. Recently, we fabricated a site-specific bone-targeting system from polymeric nanoparticles that demonstrates an ability to prevent bone loss in an osteoporotic model by interfering with Sema4d gene expression using small interference RNA (siRNA) molecules. The aim of the present investigation was to determine the effects of this targeting system on the periodontium, an area of high bone turnover. We demonstrated, by single photon emission computed tomography, that intravenous injection of this molecule in ovariectomized Balb/C mice is able to target alveolar bone peaking 4 hr post-injection. We then compared, by histological analysis, the bone volume/total volume (BV/TV), alveolar bone height loss, immunohistochemical expression of Sema4d, and total number of osteoclasts in mandibular alveolar bone. Four treatment modalities were compared as follows: (1) sham-operated, (2) OVX-operated, (3) OVX+estrogen replacement therapy, and (4) OVX+siRNA-Sema4d animals. The results from the present study demonstrate that an osteoporotic condition significantly increases alveolar bone height loss, and that the therapeutic effects via bone-targeting systems featuring interference of Sema4d are able to partly counteract alveolar bone loss caused by osteoporosis. While the future therapeutic demand for the large number of patients suffering from osteoporosis faces many challenges, we demonstrate within the present study an effective drug-delivery moiety with anabolic effects on the bone remodeling cycle able to locate and target alveolar bone regeneration.

Evidence regarding the caries-inhibiting effect of chlorhexidine varnish is inconclusive. This study investigated the caries-inhibiting effect of the varnish EC40 on pits and fissures of first permanent molars. A two-year randomized controlled trial was carried out among 461 six- to seven-year-old children. In a split-mouth design, one group of molars received EC40 at baseline, 6, 12, and 18 months, and another group at baseline, 3, 12, and 15 months. Control molars did not receive EC40. Adherence to the treatment protocol was good. The dropout rate was 17%. Blinded examiners performed dental examinations. The caries-inhibiting effects of the two EC40 application schemes were comparable. The prevented fraction of caries was 25% (95%CI, 1%, 49%, p = 0.04) after 2 years and 9% (95%CI, -11%, 29%, p = 0.20) one year after termination of the trial, suggesting a short-term benefit from the use of EC40. The efficiency of EC40 is questionable in low-caries-incidence child populations.

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