Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats.

Increasing evidence has revealed a positive correlation between postmenopausal osteoporosis and intervertebral disc degeneration, the underlying mechanism of which might be associated with changes in the vertebral bone and endplate. Alendronate (ALN) can increase bone mass and improve the microstructure of osteoporotic vertebrae, which might be helpful in preserving disc morphology and mechanical properties. This study aims to investigate the effects of ALN on lumbar intervertebral disc degeneration related to osteoporosis using an ovariectomized (OVX) rat model. Thirty female Sprague-Dawley rats aged 3 months were randomly divided into three groups (with 10 rats each) as follows: the Sham group underwent sham surgery; the OVX + ALN group had twice-a-week subcutaneous injections of ALN (15 μg/kg) for 6 months. The OVX + V group received an equivalent volume of saline solution as placebo post-OVX. After animals were sacrificed at 6 months post-OVX, the L3-6 spinal segments were harvested. Bone mineral density (BMD), micro-CT analysis and biomechanical testing were performed to evaluate the bone quality and microstructural changes in the lumbar vertebral bodies. Histological analysis with van Gieson stain and the histological score were used to identify the characteristics of the degenerative discs. The disc height and the thickness of the cartilage endplate were measured and compared. Immunohistochemistry and real-time PCR measurements for aggrecan, type I collagen, type II collagen, and matrix metalloprotease (MMP)-1, MMP-3 and MMP-13 expressions on the disc were performed to assess the underlying molecular signaling changes in matrix metabolism during intervertebral disc degeneration. The OVX + ALN group significantly maintained vertebrae BMD, percent bone volume and biomechanical strength, when compared with the OVX + V group. Histological evaluation suggests that there was no significant difference in disc height between the OVX + ALN and Sham groups, and ALN significantly prevented cartilage endplate thickening and the development of abnormal bony tissues within the cartilage endplate. The histological score in the OVX + ALN group was significantly lower than the OVX + V group, suggesting that ALN treatment was effective in delaying the process of the disc degeneration. The results of molecular analysis revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in MMP-1, MMP-3 and MMP-13 expressions at both the protein and mRNA levels in the OVX + ALN group. ALN can retard the progression of lumbar intervertebral disc degeneration in OVX rats. The underlying mechanisms might be related to preservation of the structural integrity and function of the adjacent structures, including the vertebrae and endplates, which further links with modulations in extracellular matrix metabolism to protect the disc from degeneration. These results suggest that ALN might be a promising drug agent for preventing lumbar intervertebral disc degeneration related to osteoporosis.

Luo Y ，Zhang L ，Wang WY ，Hu QF ，Song HP ，Su YL ，Zhang YZ ... -  《-》

Alendronate Prevents Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion in Ovariectomized Rats.

Zhou Z ，Tian FM ，Wang P ，Gou Y ，Zhang H ，Song HP ，Wang WY ，Zhang L ... -  《-》

Effects of alendronate on lumbar intervertebral disc degeneration with bone loss in ovariectomized rats.

Osteoporosis adversely affects disc degeneration cascades, and prophylactic alendronate (ALN) helps delay intervertebral disc degeneration (IDD) in ovariectomized (OVX) rats. However, there remains no information regarding whether ALN affects IDD with bone loss. This study aimed to observe the effects of ALN on degenerative discs with bone loss induced by OVX in rats. This study used controlled in vivo experiments in rodents. Thirty female Sprague-Dawley rats were randomly assigned to undergo sham surgery (n=10) or OVX surgery (n=20); 3 months later, the OVX animals were injected with either ALN (OVX+ALN, 15 µg/kg/2w, n=10) or normal saline (OVX+vehicle treatment [V], n=10). At 3 months after the ALN intervention, van Gieson staining and immunohistochemistry were used to investigate histologic and metabolic changes in the discs. Bone mineral density (BMD), micro-computed tomography, and biomechanical tests were conducted to determine the biological properties of the vertebrae. The OVX+ALN group exhibited significantly reduced morphologic degenerative alterations in both the nucleus pulposus and annulus fibrosus, with a markedly lower IDD score than that of the OVX+V group. The OVX+ALN samples showed increased disc height and decreased cartilage end plate thickness and bony area compared with the OVX+V group. Compared with saline, ALN administration markedly inhibited the type I collagen, matrix metalloprotease (MMP)-1, and MMP-13 expression levels while increasing the type II collagen and aggrecan expression levels in the disc matrix. Compared with the OVX+V group, OVX+ALN vertebrae revealed significantly enhanced BMD with increased biomechanical strength, as well as increased percent bone volume and trabecular thickness. ALN has favorable effects on disc degeneration with bone loss and helps to alleviate IDD while enhancing the biological and mechanical properties of vertebrae and end plates.

Song H ，Luo Y ，Wang W ，Li S ，Yang K ，Dai M ，Shen Y ，Zhang Y ，Zhang L ... -  《-》

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats.

Tian FM ，Yang K ，Wang WY ，Luo Y ，Li SY ，Song HP ，Zhang YZ ，Shen Y ，Zhang L ... -  《-》

The inhibitory effect of salmon calcitonin on intervertebral disc degeneration in an ovariectomized rat model.

Luo Y ，Zhang L ，Wang WY ，Hu QF ，Song HP ，Zhang YZ ... -  《-》