Modeling and remodeling effects of intermittent administration of teriparatide (parathyroid hormone 1-34) on bone morphogenetic protein-induced bone in a rat spinal fusion model

• The present study found that intermittent administration of PTH 1-34 significantly decreased the TV of new rhBMP-2-induced bone, following the initial formation of a fusion mass equivalent to that of the control group.
• Bone histomorphometry demonstrated predominant bone resorption at the periosteum and bone formation at the endosteum in rats receiving PTH 1-34.
• These results indicated that PTH 1-34 supported modeling of rhBMP-2-induced bone in addition to the remodeling effect which confirmed by bone histomorphometry and serum markers.

BackgroundBone morphogenetic protein (BMP)-based tissue engineering has focused on inducing new bone efficiently. However, modeling and remodeling of BMP-induced bone have rarely been discussed. Teriparatide (parathyroid hormone [PTH] 1-34) administration initially increases markers of bone formation, followed by an increase in bone resorption markers. This unique activity would be expected to accelerate the modeling and remodeling of new BMP-induced bone.MethodsMale Sprague-Dawley rats underwent posterolateral spinal fusion surgery and implantation of collagen sponge containing either 50 μg recombinant human (rh)BMP-2 or saline. PTH 1-34 (60 μg/kg, 3 times/week) or saline injections were continued from preoperative week 2 week to postoperative week 12. The volume and quality of newly formed bone were monitored by in vivo micro-computed tomography and analyses of bone histomorphometry and serum bone metabolism markers were conducted at postoperative week 12.ResultsMicrostructural indices of the newly formed bone were significantly improved by PTH 1-34 administration, which significantly decreased the tissue volumes of the fusion mass at postoperative week 12 compared to that at postoperative week 2. Bone histomorphometry and serum analyses showed that PTH administration significantly increased both bone formation and resorption markers. Analysis of the histomorphometry of cortical bone identified predominant periosteal bone resorption and endosteal bone formation.ConclusionsLong-term intermittent administration of PTH 1-34 significantly accelerated the modeling and remodeling of new BMP-induced bone.Clinical relevanceOur results suggest that the combined administration of rhBMP-2 and PTH 1-34 facilitates qualitative and quantitative improvements in bone regeneration, by accelerating bone modeling and remodeling.