Effect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial

Abstract

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T -S vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research.

Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice

“…Moreover, nerve density was higher in porous endplates than in normal endplates or degenerative nucleus pulposus 25 . Zoledronic acid and denosumab, drugs that inhibit osteoclast activities, have shown analgesic effects in patients with Modic changes associated LBP 26,27 , with the implication of a potential role of osteoclast activity in sensory nerve innervation.…”

Short tau inversion recovery MRI of Modic changes: a reliability study

“…Such data were included in articles on spondylarthritis (1)(2)(3)(4)(5), fractures (6), Modic changes (MCs) (7), hemangiomas (8), and pedicle screw loosening (9). However, all but one (6) of these reliability studies had only two observers, most (1,3-5,7-9) had small patient samples (n ¼ [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], only one (8) included measurements (of signal intensities); the spondylarthritis studies were limited to lesion detection (1)(2)(3)(4)(5). Reliability estimates differed widely in these heterogeneous studies where radiologists and non-radiologists interpreted various fat-suppressed 1.5-T or 3-T series.…”

“…The association between MCs and pain is inconsistent (13)(14)(15)(16), but edema type MCs might be symptomatic (17)(18)(19). Mechanical, autoimmune, and infectious explanations for MCs have been proposed (20), and various treatments have been and are being tested (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Reliable evaluation of the STIR findings is required to validate their relevance to symptoms and treatment (35)(36)(37).…”

Effect of Preoperative Zoledronic Acid Administration on Pain Intensity after Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures

“…Cai et al conducted a trial in patients aged >40 years who had low back pain and vertebral modic changes for 6 months. Compared with that of the placebo group, the VAS score of the ZOL group decreased significantly [ 19 ]. Liu et al analyzed the clinical data of 482 elderly patients with osteoporotic fractures.…”