Abstract
BACKGROUND: Bisphosphonates (BP) are a recommended treatment for osteoporosis and an analgesic effect has been suggested. Magnesium is involved in pain mechanisms, mood disorders and also in bone homeostasis. Association of BPs and magnesium has however not been studied to explore pain processes in post-menopausal osteoporosis. METHODS: In this pilot ancillary study of a randomized clinical trial in post-menopausal osteoporosis, women were randomized to standard care with intravenous Zoledronate (BP group, n = 22) or BP with oral magnesium (BPMg group, n = 22), 200 mg/day for 3 months. Endpoints were quantified before and 1 year after treatment as spontaneous pain, anxiety, depression and sleep quality, as well as quantitative sensory testing of pain sensitivity by thermal thresholds and conditioned pain modulation (CPM), a psychophysical marker of the functionality of pain modulation at spinal level. RESULTS: Thirty-five women (68.2 ± 7.3 years old) with post-menopausal osteoporosis completed the analysis. Compared with baseline, magnesium supplementation did not change significantly any of the endpoints. CPM at baseline was low (-0.92 ± 1.14) and not reversed by treatment. CONCLUSIONS: This study in post-menopausal osteoporosis underlines for the first time that zoledronate or zoledronate with magnesium have no effect on pain characteristics and thresholds. It shows a dysfunction of pain inhibitory pain pathways and its non-reversibility with treatments. It points towards the lack of any analgesic effect of zoledronate, and above all to a latent vulnerability of osteoporotic women who are at a potential risk of fracture with a poor pain modulation that needs to be researched further to limit future chronification. TRIAL REGISTRATION NUMBER: (NCT05328154), 15/03/2022. TRIAL: Protocol, statistical analysis plan, participant data and other materials (including data dictionary) can be accessed on request to the corresponding author.