Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial

Abstract

Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation‐ (FES‐) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES‐rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES‐rowing alone with FES‐rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV ( p = 0.05 to 0.006), the CTI ( p = 0.009), and the BR ( p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing‐only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia ( p = 0.05). A subgroup analysis of the rowing‐only arm showed that gains in the CSI at the tibial metaphysis varied in a dose‐dependent fashion based on the total amount of exercise performed ( p = 0.009). These findings demonstrate that the osteogenic response to FES‐rowing is dose‐dependent. Combination therapy with ZA and FES‐row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Spinal Cord Injury as a Model of Bone-Muscle Interactions: Therapeutic Implications From in vitro and in vivo Studies

“…Considering the promising role of FES rowing exercise in promoting muscle contraction with combined mechanical loading of lower limb long bones in SCI patients, a therapeutic synergism with drugs acting at the bone level has been proposed (82). This combined strategy could induce both bone resorption inhibition and bone neoformation stimulation.…”

“…This combined strategy could induce both bone resorption inhibition and bone neoformation stimulation. A randomized clinical trial comparing FES-rowing alone with FES-rowing plus zoledronic acid (a powerful bone anti-resorptive drug), have been carried out to investigate the impact of bone health in SCI (82). The latter group had significantly greater cortical bone volume (CBV) and cortical thickness index (CTI) at both distal femoral and proximal tibial metaphyses, compared to the FES-rowing-only group.…”

A Primary Care Provider's Guide to Bone Health in Spinal Cord-Related Paralysis

“…23,24 The role of bisphosphonates administration on increasing bone mass at the knee (distal femur and proximal tibia), the area most susceptible to fractures in patients with SCI/D, is more controversial, with some studies showing no significant benefit 25 and others showing increase in bone mass. 26,27 Teriparatide, which increases osteoblastic activity (thus bone deposition), may have positive effect on increasing bone density of the spine, hip, and knee in individuals with SCI/D-related paralysis, 28 but no studies utilized fracture occurrence as outcomes, thus efficacy in fracture prevention was not assessed.…”

Effect of Adapted Ergometer Setup and Rowing Speed on Lower Extremity Loading in People with and without Spinal Cord Injury

“…Previous studies reported inconsistent bone responses after training with FES-rowing [9][10][11] and a wide range of foot reaction forces generated by SCI rowers (0.22 to 0.67 body weight (BW)) [12][13][14] .…”

“…FES-rowing is one exercise intervention that is growing in popularity in SCI rehabilitation 8 . Previous studies reported inconsistent bone responses after training with FES-rowing 9–11 and a wide range of foot reaction forces generated by SCI rowers (0.22 to 0.67 body weight (BW)) 12–14 . These variable results, combined with observations that bone adapts to its mechanical loading environment, suggest that foot loading influences subsequent changes in lower extremity bone in FES-rowing.…”