Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats

JBMR Plus, 2023 · DOI: 10.1002/jbm4.10825 · Published: December 1, 2023

Spinal Cord Injury Pharmacology Musculoskeletal Medicine

Simple Explanation

This study investigates a new treatment (NP159) for bone loss after spinal cord injury (SCI) in rats. SCI leads to rapid bone loss, and current treatments have limitations. The study found that NP159 prevents bone loss and preserves bone strength after SCI in rats. NP159 works by inhibiting bone resorption (breakdown) while maintaining bone formation, unlike other treatments that inhibit both. This unique action may make it a better option for treating bone loss after SCI. The results suggest NP159 could be a promising therapeutic agent for mitigating bone loss, not only after SCI but also in other conditions associated with severe immobilization.

Study Duration

8 weeks

Participants

4-month-old male Wistar rats

Evidence Level

Level III, Animal study

Key Findings

1
NP159 treatment almost completely prevents the deterioration of bone after SCI, including loss of bone mineral density, trabecular bone volume, trabecular connectivity, and bone stiffness.
2
NP159 greatly inhibits bone resorption while maintaining bone formation after acute SCI, as shown in blood and histomorphometric analyses.
3
In ex vivo cultures, NP159 reduces osteoclastogenesis (formation of bone-resorbing cells) while increasing osteoblastogenesis (formation of bone-building cells).

Research Summary

The study demonstrates the efficacy of Siglec-15 Ab (NP159) in reducing bone resorption after acute SCI while maintaining bone formation capacity in rats. NP159 almost fully prevents the SCI-induced loss of bone mass and preserves trabecular microarchitecture in a rat model of acute motor-complete spinal cord transection. NP159 decreases osteoclast maturation and bone resorption while increasing osteoblastogenesis to maintain bone formation in SCI.

Practical Implications

Potential Therapeutic Agent

Siglec-15 Ab (NP159) may hold greater promise as a therapeutic agent compared to currently used antiresorptive or anabolic agents.

Improved Rehabilitation

Improving skeletal integrity with NP159 in persons with chronic SCI could increase the number of individuals eligible for rehabilitation strategies and modalities for gait.

Broader Application

Siglec-15 Ab could potentially extend to other disuse conditions that result in severe osteoporosis, not only after SCI but also in other disuse conditions.

Study Limitations

1
Whether this agent can reverse the bone loss in chronic SCI has yet to be tested.
2
Only male rats were studied. It thus remains of interest and relevance to investigate whether the beneficial effects can be extended to females.
3
Substantial “rebound” bone loss has been reported following discontinuation of DMAB treatment, and this may also be a clinical concern when discontinuing NP159 treatment

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