Background/Purpose:   Osteoporotic patients with no evidence of fractures sometimes experience vague lower back pain. However, there have been few reports regarding the correlation between osteoporosis and pain-related behavior. Our previous studies have indicated that hindlimb-unloading induced bone loss and mechanical hyperalgesia in hindlimb of mice. We investigated the effects of osteoporosis treatments on bone mass and pain-related behaviors in osteoporosis model mice with hindlimb unloading.

Methods:   Male ddY mice (8 weeks old) were tail-suspended for 2 weeks and assigned to 4 groups; hindlimb-loaded mice treated with vehicle (control=HL), hindlimb-unloaded mice treated with vehicle (HU), hindlimb-unloaded mice treated with ALN (HU-ALN), hindlimb-unloaded mice treated with PTH (HU-PTH) (n=8/group). After 2 weeks tail-suspension, mice were reloaded and started treatment. For 2 weeks, mice were injected subcutaneously with 40μg/kg ALN twice a week, 40μg/kg PTH five times a week, or saline as vehicle. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by micro-computed tomography (μCT) 2 weeks after reloading and treatment. Mechanical sensitivity was also tested using von Frey filaments 2 week after reloading. The withdrawal threshold, the 50% withdrawal threshold and the frequency of the withdrawal response to the application of von Frey filaments to the plantar surface of the hind paws was examined. Measurement of pain-related behavior with von Frey filaments was interpreted as indicative of mechanical allodynia.

Results: μCT analysis of the distal femoral metaphysis and the proximal tibial metaphysis showed that significantly decreased bone volume/tissue volume (BV/TV) was significantly decreased in HU group compared with HL group. However, ALN treatment and PTH treatment increased BV/TV compared with saline in HU mice. (Fig.1) The paw withdrawal threshold and the 50% paw withdrawal threshold were significantly lower in HU group than in HL group, whereas it was significantly higher in HU-ALN group than in HU group. Similarly, it was tend to be higher in HU-PTH group than in HU group, but not significantly. (Fig.2) The paw withdrawal frequency stimulated by von Frey filaments with strength of 0.4-1.0 g was significantly higher in HU group than in HL group. Whereas it was significantly lower in HU-ALN group and HU-PTH group than in HU group with strength of 0.4-0.6g.

Conclusion: In this study, treatment of ALN or PTH recovered bone loss and mechanical hyperalgesia in disuse osteoporotic animal models by hindlimb-unloading. The results suggest that low bone volume itself is one of the causes of osteoporotic pain. (Fig.1) (Fig.2)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-osteoporosis-treatments-for-bone-loss-and-pain-related-behavior-in-the-hind-limb-unloaded-mouse-model-of-disuse-osteoporosis/