Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model

Abstract

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

The slow release of BMP-7 at a low dose accelerates dental implant healing in an osteopenic environment

“…In addition, a sustained release over time from a confined compartment not only assures a long-term ongoing osteogenic activity, but also provides maximum efficacy (being the delivery system directed specifically to the targeted cell pools) as well as mimics the physiological mode Dental implant healing in an osteopenic environment of growth factor release from the bone matrix during bone remodelling (Liu et al, 2018;Liu et al, 2005). Other approaches to deal with the enhancement and acceleration of bone formation and implant osseointegration under osteopenic/osteoporotic conditions have been described, such as the local delivery of BMP-4 (Lai et al, 2011), the use of injectable tricalcium phosphate (TCP)-microspheres associated with BMP-2 (Chang et al, 2017), the local application of anti-cytokine antibodies (Yang et al, 2020) or the use of systemic sclerostin antibody treatment (Korn et al, 2019;Virdi et al, 2015). Another approach suggested relates to the presurgical injection of BMP-7 in a slow-release system [polyglycolic acid (PLGA)-microspheres] to initially build up local bone structure before implant placement (Phillips et al, 2006).…”

Osseointegration of Dental Implants and Osteoporosis

“…Osteocytes play an active role in modulating the process of bone metabolism through the lacunocanalicular system [57,58]. Studies in osteoporotic animal models have shown altered osseointegration, especially in trabecular bone, which resulted in a significant reduction in bone-implant contact [59][60][61].…”

The impact of medication on osseointegration and implant anchorage in bone determined using removal torque—A review

“… Femur 56 33.6 0.0 ( Yi et al., 2017 ) OVX ± Odanacatib h.d. 98.4 6.9 SOSTab Systemic Rat, Wistar OVX ± SOSTab Tibia 14 16.8 37.6 ( Korn et al., 2019 ) 28 7.9 125.7 Zoledronate + SOSTab Local + Systemic Rat, Wistar OVX + SOSTab ± Zoledronate Tibia 14 4.7 32.1 ( Korn et al., 2019 ) 28 102.8 440.1 Raloxifene Local Rat, SD ± Raloxifene † Tibia 28 66.7 - ( Harmankaya et al., 2013 ) Raloxifene Systemic Rat, Wistar OVX ± Raloxifene Tibia 42 323.0 302.2 ( Ramalho-Ferreira et al., 2015 ) hPTH Systemic Rat, SD ± hPTH ∗∗ Tibia 28 218.2 - ( Skripitz and Aspenberg, 2001 ) hPTH Systemic Rabbit, NZW ± hPTH Tibia 28 28.1 - ( Corsini et al., 2008 ) 56 21.8 - hPTH ...…”