Sclerostin Antibody Reverses the Severe Sublesional Bone Loss in Rats After Chronic Spinal Cord Injury

Calcif Tissue Int., 2018 · DOI: 10.1007/s00223-018-0439-8 · Published: October 1, 2018

Spinal Cord Injury Musculoskeletal Medicine

Simple Explanation

This study investigates whether blocking sclerostin, a protein that inhibits bone formation, can reverse bone loss in rats with long-term spinal cord injury (SCI). The researchers treated rats with chronic SCI with a sclerostin antibody (Scl-Ab) and found that it helped restore bone density and strength. The findings suggest that Scl-Ab could be a potential treatment for reversing bone loss in people with chronic SCI.

Study Duration

8 weeks

Participants

Male Wistar rats (275 g)

Evidence Level

Not specified

Key Findings

1
Scl-Ab treatment significantly increased bone mineral density (BMD) at the distal femur, proximal tibia, and lumbar spine in rats with chronic SCI.
2
Scl-Ab administration after SCI completely restored trabecular bone volume and structure, primarily by increasing trabecular thickness.
3
Scl-Ab enhanced bone formation by increasing osteoblast activity, bone formation rate, and osteoid indices in animals with chronic SCI.

Research Summary

This preclinical study demonstrates that sclerostin antibody (Scl-Ab) can reverse sublesional bone loss in rats with chronic motor-complete spinal cord injury (SCI). Treatment with Scl-Ab restored bone mineral density (BMD), bone structure, and bone mechanical strength, and increased bone formation in animals with chronic SCI. The study suggests that sclerostin antagonism may be a valid clinical approach to reverse the severe bone loss that invariably occurs in patients with chronic SCI.

Practical Implications

Potential Treatment for Chronic SCI Bone Loss

Sclerostin antibody immunotherapy could be a means to reverse bone loss in individuals with chronic SCI, in addition to preventing bone loss shortly following acute SCI.

Improved Bone Health Outcomes

The reversal of bone loss and restoration of bone structure with Scl-Ab treatment could reduce fracture occurrence at sublesional skeletal sites in SCI patients.

Clinical Trial Rationale

The findings provide a strong rationale for initiating clinical trials to evaluate the effectiveness of sclerostin antibody immunotherapy in individuals with chronic SCI.

Study Limitations

1
The study was conducted on rats, and the results may not be directly translatable to humans.
2
The optimal dose and duration of Scl-Ab treatment for reversing bone loss in chronic SCI need to be further investigated.
3
The long-term effects of Scl-Ab treatment on bone health and fracture risk in individuals with chronic SCI are unknown.

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