Bone Abstracts

Introduction: Indirect inhibition of the extracellular BMP antagonist network and the activation of Wnt signaling by PTH1-34 suggest the possibility of synergistic effect on bone regeneration by the co-administration of BMP and PTH1-34.

Materials and methods: In a rat critical-sized femoral defect (7 mm) model, SD rats (n=32) were operated by absorbable collagen sponge containing two different BMP-2 dosage treatments; 1) 2 μg (low dose) and 2) 50 μg (high dose). Each of the BMP treatments was studied in combination with intermittent PTH1-34 (180 μg/kg per w) or saline injection starting 2 w before the operation and continuing until 8 w after operation. Microstructural indices (TV, BV, BV/TV, Tb.Th) of the newly formed bone and and fusion status were evaluated by μCT (post-op. 0, 1, 2, 4, 6, 8 w). The serum markers of bone metabolism were also quantified (post-op. 4 and 8 w).

Results: Fusion rates at post-op. 8w were not significantly different w/ or w/o PTH1-34 administration. (Saline/PTH1-34: BMP; 2 μg 75%/100%,50 μg; 100%/100%). Microstructural indices of the newly formed bone (BV/TV, Tb.Th) were signifi2cantly improved by PTH1-34 administration in both BMP dose groups. Time-dependent changes demonstrated that the TV in the BMP high dose group significantly increased by PTH1-34 administration (PTH1-34: 77.6±29.2 mm³, saline: 34.6±4.9 mm³, P<0.001). Serum levels of osteocalcin and P1NP were significantly increased by PTH1-34 in both BMP dose groups (BMP low group: P<0.01, BMP high group P<0.05).

Discussion and conclusions: Intermittent administration of PTH1-34 significantly increased the quality of the newly formed bone in the BMP treatment groups. However, the remodeling of newly formed bone in BMP high dose group was not apparent in this study (with internal fixation) compared to that in our previous rat spinal fusion model (without fixation) (Morimoto et al. 2014). PTH may accelerate the remodeling process of the newly formed bone in response to mechanical stress.