calcitonin and Intervertebral-Disc-Degeneration

Intervertebral disc degeneration related to postmenopausal osteoporosis is an important issue in spinal disorder research. This study aimed to investigate the effects of salmon calcitonin (sCT), as an antiresorptive medication, on lumbar intervertebral disc degeneration using a rat ovariectomy (OVX) model.. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: the sham-operated (Sham) group and two ovariectomized groups treated with vehicle (OVX+V) or sCT (OVX+CT; 16 IU/kg, sc) on alternate days for 6 months. Treatment began after OVX and continued for 6 months. At the end of the experiment, bone mineral density (BMD), micro-CT analysis, biomechanical testing, histology, and immunohistochemistry were performed for all groups.. Salmon calcitonin significantly maintained vertebrae BMD, percent bone volume, and biomechanical strength, when compared with the OVX+V group. The changes of mucoid degeneration in the nucleus pulposus and calcification in the middle cartilage endplate were more moderate in the OVX+CT group compared with the OVX+V group, and immunohistochemistry revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 expressions in the OVX+CT group.. Salmon calcitonin treatment was effective in delaying the process of the disc degeneration in OVX rats. The underlying mechanisms may be related to preservation of structural integrity and function of vertebrae, and affecting extracellular matrix metabolism by modulating the expressions of MMPs, aggrecan and type II collagen to protect the disc from degeneration.

Topics: Animals; Biomarkers; Bone Density; Bone Density Conservation Agents; Calcitonin; Female; Intervertebral Disc Degeneration; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley

We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae.. The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats.. We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression.. At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats.. Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

Topics: Animals; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitonin; Collagen Type II; Drug Evaluation, Preclinical; Female; Intervertebral Disc Degeneration; Lumbar Vertebrae; Matrix Metalloproteinase 1; Matrix Metalloproteinase 13; Ovariectomy; Stress, Mechanical; X-Ray Microtomography