Zoledronic acid for chronic low back pain associated with Modic changes. Efficacy for low back symptoms, effect on magnetic resonance imaging findings and serum biomarkers in a randomized placebo-controlled study

Abstract Low back pain (LBP) is a common symptom among people of all ages and its economic costs are comparable to the costs of cardiovascular diseases, cancer and mental health. Modic changes (MC) are vertebral endplate (EP) and bone marrow changes associated with intervertebral disc degeneration, which are visualized on magnetic resonance imaging (MRI). MC are associated with LBP, type 1 MC (M1) more strongly than other MC types. Effective treatments for LBP related to MC are lacking. Bisphosphonates such as intravenously administered zoledronic acid (ZA), may be a potential treatment option because of its beneficial effect on bone marrow lesions and on pain symptoms in osteoarthritis.

This randomized controlled study evaluated the efficacy of a single intravenous infusion of 5 mg of ZA (n=20) in comparison to a saline infusion (n=20) for LBP associated with MC. The effect was evaluated on the basis of LBP intensity and disability, the type and size of MC lesions and serum biomarkers, especially inflammatory and bone turnover markers. ZA reduced LBP intensity in the short term at one month and reduced the use of NSAIDs at one year. ZA tended to speed up the conversion of M1-dominant to type 2-dominant MC and decreased the size of M1-dominant MC, although statistical significance was not reached. Different trends were observed in the serum biomarkers of the ZA and placebo groups. At one year, the concentration of the chemokine IP-10 was elevated in the ZA group and reduced in the placebo group, whereas two bone metabolism biomarkers (AFOS and iPINP) had decreased in the ZA group. In conclusion, ZA is a promising treatment for MC-associated LBP. However, future studies with larger sample size are required.