Effect of aging on bone formation induced by recombinant human bone morphogenetic protein‐2 combined with fibrous collagen membranes at subperiosteal sites

Abstract

This study was designed to examine the effect of aging on bone formation induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a fibrous collagen membrane (FCM). Implantation was done subperiosteally in bilateral palatal grooves in 34 male Wistar rats divided into three age groups: a 10-week-old group (10w group), a 30-week-old group (30w group) and a 70-week-old group (70w group). RhBMP-2-combined FCMs were implanted on the left palatal grooves as BMP-implanted sites (BMP site), while rhBMP-2 was not implanted on the right palatal grooves as control sites. The rats were sacrificed 6 weeks after implantation, and histometric evaluations were performed. New bone formation was observed in every site of each age group and the new bone was almost completely continuous with the original bone. The new bone volume (NBV) of the BMP site was significantly higher than that of the control site in each age group. The NBV of both the control and BMP sites were highest in the 10w group and lowest in the 70w group. The disparity of NBV between the control and BMP sites, which indicated the response to implanted BMP excluding the effect of skeletal growth and surgical stimulation, did not significantly differ among the age groups. These results indicate that rhBMP-2-combined FCM has the ability to induce new bone formation continuous with original bone even in senescent rats. Furthermore, it appeared that, in the case of palatal subperiosteal implantation, the responsiveness to implanted BMP was independent of age, although the total volume of newly formed bone declined with aging.

The Use of Cancellous Bone-Block Allograft for Reconstruction of the Atrophic Alveolar Ridge

“…Our findings of a significantly greater percentage of new bone formation in younger patients relative to older ones following remodeling with cancellous block-allograft in the anterior atrophic maxilla and posterior atrophic mandible (Nissan et al, 2011d;Nissan et al, 2011e) agree with earlier studies of the effect of age on new bone formation (Fisher et al, 2010;Matsumoto et al, 2001;Rando, 2006;Tanuka et al, 1996;Walboomers et al, 2006). Following induction of injury to the tibia marrow cavity in a rat model, MicroCT and histomorphometry revealed a reduced response with an increase in age, suggesting that the restoration of normal tissue is age-dependent (Fisher et al, 2010).…”

“…Others also noted differences in the osteogenic properties of bone marrow-derived osteoblast-like cells by donor age (Walboomers et al, 2006). In a study of bone formation induced by recombinant human bone morphogenetic protein-2 in male Wistar rats, the total volume of newly formed bone declined with aging (Matsumoto, et al, 2001). The reasons for the age-related decline in tissue repair are not well understood.…”

Targeting the osteoblast: approved and experimental anabolic agents for the treatment of osteoporosis

“…rhBMP-2 induced bone formation in rat models, but its effect declined with age. 157 In a mouse model, 158 rhBMP-2 induced bone formation; the observed bone mass increase was associated with an increase in MSCs numbers, osteogenic activity and proliferation, and a decrease in apoptosis. Similarly, systemically administered 125 I-BMP-6 increased bone volume and mechanical characteristics of both the trabecular and cortical bone, thereby improving microarchitecture and quality of the skeleton in osteoporotic rats.…”

Inhibition of Microtubule Assembly in Osteoblasts Stimulates Bone Morphogenetic Protein 2 Expression and Bone Formation through Transcription Factor Gli2

“…BMP-2 was also recently recognized as an osteoporosis-associated gene by human polymorphism studies (49). Animal studies have found that both gene expression and anabolic activity of BMP-2 are significantly decreased in aging bones (11,29,31,50,58). These results suggest that BMP-2 gene expression is necessary for maintenance of postnatal bone formation, particularly during aging, and that progressive, age-related loss of BMP-2 function may be one of the molecular mechanisms involved in the development of osteoporosis.…”

“…Microtubule inhibition had no effect on canonical Wnt VOL. 29,2009 INHIBITION OF MICROTUBULE ASSEMBLY STIMULATES BMP-2 1293…”