کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2780465 1153299 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening
چکیده انگلیسی

Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 μg /kg/day), an extreme dose of alendronate (200 μg/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 48, Issue 2, 1 February 2011, Pages 225–230
نویسندگان
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