Intermittent administration of teriparatide enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis

Abstract

Background context: There has been no study regarding the effect of intermittent administration of teriparatide (TPTD [recombinant human parathyroid hormone (1-34)]) on spinal fusion in patients with glucocorticoid-induced osteoporosis (GIOP).

Purpose: To elucidate the effect of intermittent administration of TPTD on spinal fusion in rats with GIOP.

Study design: An experimental animal study of rats under continuous glucocorticoid (GC) exposure undergoing spinal fusion surgery and administration of TPTD or saline.

Methods: Male 8-week-old rats (n=18) were administered 5 mg/kg methylprednisolone (MP) for 12 weeks. After 6 weeks of MP administration, the rats underwent posterolateral spinal fusion (L4-L5) with iliac crest autograft. Then, five times a week, they were given either saline or 40 μg/kg TPTD for 6 weeks. The following assessments were performed: time-course bone microstructural analysis of the fusion mass and adjacent vertebrae (L6), with in vivo microcomputed tomography (μCT); fusion assessment, with manual palpation testing and three-dimensional CT images; and bone histomorphometrical analysis of the fusion mass.

Results: In the TPTD group, values for bone volume and other bone microstructural parameters at the fusion mass increased and peaked 4 weeks after surgery, and these values were significantly greater than those for the control (CNT) group at 4 and 6 weeks after surgery. Fusion assessment showed that fusion rate was higher in the TPTD group than in the CNT group (CNT group: 56%, TPTD group: 89%). Bone histomorphometry revealed that values for bone formation parameters were significantly higher in the TPTD group than in the CNT group.

Conclusions: Under continuous GC exposure in a rat model of spinal fusion, intermittent TPTD administration accelerated bone modeling and remodeling predominantly by stimulating bone formation at the fusion mass and increasing the fusion rate. Intermittent TPTD administration also improved bone microarchitecture of adjacent vertebrae.

Keywords: Adjacent vertebrae; Bone graft; Bone remodeling; Glucocorticoid-induced osteoporosis; Spinal fusion; Teriparatide.