Bisphosphonate Therapy for Degenerative Disc Disease?

Gologorsky, Yakov; Chi, John

doi: 10.1227/01.neu.0000435113.33768.2d
Science Times

    Investigations into the pathogenesis of interverterbral disc degeneration have implicated age, vertebral body integrity, endplate changes, and changing hormonal milieu, among other factors. The precise relationship between osteoporosis and lumbar disc degeneration, however, is yet unanswered in the literature. While some clinical and epidemiological studies have suggested that soft, osteoporotic bone cushions the intervertebral disc, animal studies have concluded that, in fact, the osteoporotic vertebral body has decreased marrow perfusion which is unfavorable for the diffusion of nutrients into the disc and accelerate disc degeneration. Similarly, changes in the cartilaginous endplate composition are seen in the osteoporotic spine, with increased thickness, more bony changes, and increased expression of type X collagen, which results in abnormal disc loading and decreased nutrient supply to the disc.

    Overall, the osteoporotic spine may be predisposed to accelerated disc degeneration. The observation that menopause (or other forms of estrogen deprivation) results in accelerated disc degeneration has engendered studies that have examined the role of interventions, such as bisphosphonates, in slowing or reversing osteoporosis and degenerative disc disease.

    Luo, et al (Bone, 2013. 55: 439-448) examine the role of alendronate (ALN) in decreasing measures of lumbar disc degeneration in ovariectomized rates. In their study, 30 female rats aged 3 months were randomly divided into three groups (10 rats each): the control group underwent sham surgery (ie, ovaries exteriorized but not removed); the ovariectomized (OVX) + ALN group had biweekly subcutaneous injections of ALN; The OVX + saline group received an equivalent volume of saline solution as placebo post-OVX. The animals were sacrificed 6 months later, and the L3-6 segments were harvested and analyzed with regards to bone mineral density (BMD), endplate measurements, micro-CT analysis, biomechanical testing, histological evaluation, and immunohistochemical assays.

    Overall, the OVX + ALN group significantly preserved vertebral BMD, percent bone volume and biomechanical strength, when compared with the OVX + V group. Histologically, there was no significant difference in disc height between the OVX + ALN and control groups, and ALN significantly retarded cartilage endplate thickening and bony degeneration. The results of molecular analysis revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in matrix metalloproteases (MMP) 1, 3, and13 expressions at both the protein and mRNA levels in the OVX + ALN group, suggesting actual modulation of extracellular matrix metabolism in the annulus fibrosus and nucleus pulposus.

    Although the exact pathogenesis is still unclear, disc degeneration results from a combination of mechanically-driven and biologically-mediated factors. The extracellular milieu is constantly in flux and balanced by the synthesis, breakdown, and accumulation of matrix macromolecules. The authors have shown that alendronate can influence disc degeneration by modulating many of these factors. The administration of alendronate results in preservation of the structural integrity and biomechanical function of the vertebrae and endplate, both of which are essential structures for maintaining disc function. Biologically, ALN can also influence the extracellular matrix metabolism by modulating the expressions of MMP-1, MMP-3, MMP-13, aggrecan and type I/II collagen, all of which theoretically act synergistically to protect the disc from degeneration.

    As it stands now, when clinicians are confronted by patients asking if there are any medicines that help the health of discs, we are at a loss. Though these laboratory findings may not correlate with clinical outcomes in humans, the allure of this study is that it provides groundwork for future trials investigating the benefits of bisphosphonates as well as other targets for research. In an era of increasing scrutiny of healthcare costs and mounting emphasis on preventative measures, perhaps one day, clinicians will count bisphosphonates in their arsenal of medicines that help slow degenerative disc disease.

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