Prostaglandin EP4 receptor agonist augments fixation of hydroxyapatite-coated implants in a rat model of osteoporosis

Abstract

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

Calcium-phosphate-coated Oral Implants Promote Osseointegration in Osteoporosis

“…The push-out force required to loosen the CaP-coated implant was approximately 3-fold higher compared with that for the control implants. These results corroborate earlier findings with plasmasprayed CaP-coated implants under osteoporotic conditions (Hara et al, 1999;Rocca et al, 2001;Hayashi et al, 2005). The histological difference in trabecular bone response adjacent to the CaP-implants was significant at 8 wks in our study.…”

“…a significant role in the biomechanical fixation of implants (Hara et al, 1999;Hayashi et al, 2005). Conversely, it must be emphasized that some authors failed to show significant %BIC of CaP-coated implants in osteoporotic conditions (Vidigal et al, 2009).…”

“…Further, histological evaluation revealed that CaP coatings were mainly observed to influence bone regeneration near the implant and not in the defined 500-µm ROI around the implants, as in previous work (Alghamdi et al, 2013), or in 250 µm ROI, as in the present study. This indicates that a mature portion of bone in direct contact with CaPcoated implants is mechanically very important and predictive for clinical implant survival, especially in challenging bone conditions (Hara et al, 1999;Rocca et al, 2001;Fini et al, 2004;Hayashi et al, 2005).…”

Comparative in vitro study regarding the biocompatibility of titanium-base composites infiltrated with hydroxyapatite or silicatitanate

“…Both types of osseointegration have potential applications, however in vivo studies are required to clarify the most suitable type of implant depending on the site of implantation (considering the mechanical load and the type of bone in need of repair) as well as the associated pathological conditions such as osteoporosis. Despite some limitations regarding the mechanical properties of porous apatite ceramics, the excellent osteoconductivity of HA coatings and the possibility of associating bioactive molecules (such as proteins, aminoacids, antibiotics, growth factors, anticancer and anti-osteoporosis drugs) to calcium phosphate indicate the potential advantages of the use of this type of coating especially in osteopenic bone repair [77,78]. On the other hand, the osseoinductive properties of SiO 2 -coated Ti implants (as described in our study) and their ability to promote angiogenesis and enhance neocartilage formation [73], can provide other important applications in implantology, especially for repairing bones at sites where mechanical strength is of lesser importance.…”

Effects of a new conjugate drug in a rat model of postmenopausal osteoporosis

“…Moreover, several studies using the agonist ONO--4819 have demonstrated a variety of anabolic effects, such as stimulation of osteoblast differentiation 214,215 , increased cortical bone formation in response to mechanical loading 216 , and accelerated cortical bone repair after femoral drill--hole injury 217 . Furthermore, ONO--4819 can also improve fixation of hydroxyapatite (HA)--coated implants in OVX rats by increasing the osteoconductivity of the HA coating and strengthening the bone--implant attachment 218 . 31 However, despite their anabolic effects, EP4 agonists also have drawbacks.…”