# Pain after osteoporotic fractures using mouse models and patient samples

## TL;DR

This study explores whether osteoporosis and fractures cause chronic pain using mouse models and patient data, finding that bone loss alone may not cause pain but could worsen it after fractures.

## Contribution

The study is novel in combining mouse models of osteoporosis and fracture with patient serum analysis to investigate mechanisms of pain in osteoporotic fractures.

## Key findings

- Ovariectomy alone did not induce pain behaviors or alter nociceptive gene expression in mice.
- Osteotomy affected pain behaviors in mice, and OVX worsened weight-bearing after fracture.
- Clinical analysis found no correlation between serum nerve markers and fracture pain in patients.

## Abstract

Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone and dorsal root ganglia (DRGs). It also quantifies nerve markers in serum of patients with or without osteoporotic fractures and pain.

Ovariectomy (OVX) or Sham surgery (Sham-OVX) of C57/Bl6 mice was performed (n = 10/group) and evoked and spontaneous pain behaviours assessed. In another experiment, OVX or Sham-OVX mice underwent a femoral osteotomy or sham osteotomy (n = 8/group) and pain behaviours measured. Gene expression of pain markers in bone and DRGs was quantified by RT-PCR. Nerve markers were quantified in serum of osteoporotic patients with or without fractures and pain using specific ELISAs.

OVX did not cause changes in pain behaviours nor alter nociceptive gene expression in bone and DRGs. Osteotomy and Sham osteotomy both affected pain behaviours in mice compared to non-operated controls but did not significantly change nociceptive gene expression in bone and DRGs. OVX before osteotomy worsens weight-bearing compared to Sham-OVX. Fracture and pain did not affect nerve markers expression levels in serum of osteoporotic patients.

This study demonstrates that OVX and subsequent bone loss in mice are insufficient to induce pain behaviours but may intensify pain after fracture. Our clinical analysis does not show a correlation between circulating nerve markers and fracture pain reported by the patients but suggests possible sex differences in pain markers that need to be further investigated.

The online version contains supplementary material available at 10.1007/s00774-025-01677-w.