Teriparatide attenuates vertebral destruction and modulates bone remodeling in a rat model of pyogenic
Yo Morishita1, Yuji Kasukawa1, Michio Hongo1
1Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Background Context:
Pyogenic spondylodiscitis can lead to progressive vertebral destruction and structural failure despite adequate infection control. However, pharmacologic strategies that preserve vertebral structure and support reparative bone remodeling in infected vertebrae remain insufficiently investigated.
Purpose:
This study investigated whether teriparatide (TPTD) attenuates vertebral destruction and modulates bone remodeling in a rat model of pyogenic spondylodiscitis.
Study Design:
Preclinical in vivo animal study.
Methods:
Pyogenic spondylodiscitis was induced in 12-week-old male Sprague-Dawley rats by percutaneous inoculation of methicillin-susceptible Staphylococcus aureus into the Co6/7 intervertebral disc space. Rats were assigned to vehicle control or TPTD treatment (n = 9-10 per group) and evaluated at 2 or 6 weeks. Vertebral destruction, disc height, cancellous radiodensity, and trabecular microarchitecture were assessed by micro-computed tomography. Bone histomorphometry and bone-corrected IL-6-positive area were also evaluated. This study was supported by departmental research funds ($10,000-$50,000); the authors identified no study-specific conflict of interest-associated biases.
Results:
At 2 weeks, most outcomes did not differ significantly between groups. At 6 weeks, the TPTD group showed a significantly lower vertebral destruction rate and higher cancellous radiodensity than the Control group. The vertebral destruction rate increased significantly from 2 to 6 weeks in the Control group, whereas no significant progression was observed in the TPTD group. Disc height ratio did not differ between groups at either time point. TPTD also increased BV/TV and Tb.Th and decreased Tb.Sp, with higher Conn.D observed at both 2 and 6 weeks. Histomorphometric analysis at 6 weeks demonstrated lower Oc.S/BS and higher Ob.S/BS in the TPTD group. In addition, bone-corrected IL-6-positive area was significantly lower in the TPTD group at 6 weeks.
Conclusions:
TPTD attenuated progression of vertebral destruction and improved trabecular microarchitecture in infected vertebrae. These changes were accompanied by a shift toward reparative bone remodeling and a reduction in bone-corrected IL-6-positive area.
Clinical Significance:
These preclinical findings raise the possibility that TPTD could be evaluated as an adjunct to standard management of pyogenic spondylodiscitis, particularly in patients with coexisting osteoporosis. Further studies incorporating antibiotic treatment and models of persistent infection are needed to clarify its translational relevance and potential clinical applicability.