Medication Activates Dormant Bone Cells to Ease Lower Back Discomfort

In positive developments for the 80% of Americans experiencing lower back pain during their lifetime, scientists have discovered that repurposing an existing drug can effectively target dormant osteoclast cells, reducing spinal hypersensitivity.

Xu Cao, a senior author and Orthopedic Surgery professor at Johns Hopkins University School of Medicine, explained that while osteoclasts play a crucial role in bone remodeling and skeletal development, senescence in the endplate of the spinal column leads to nerve growth and spine pain. The research indicates that eliminating these senescent osteoclasts, potentially through the use of existing drugs, could present a novel approach to treating lower back pain.

Unlocking Navitoclax’s Potential

The drug in question is an experimental anticancer medication called Navitoclax, initially known as ABT263, developed by the US pharmaceutical company AbbVie. Previous research has demonstrated the drug’s potential beyond cancer treatment, showing effectiveness in rejuvenating skin cells and addressing Alzheimer’s disease.

In the realm of geroscience, which focuses on age-related diseases, cellular senescence is a central area of investigation. Senescent cells, ceasing division but persisting without proper elimination, contribute to inflammation and various age-related chronic conditions.

Navitoclax, categorized as a senolytic, belongs to a new class of drugs targeting cellular dysfunction associated with aging to extend both healthspan and lifespan. Concerning osteoclasts, these senescent cells, instead of fulfilling their bone breakdown role for tissue remodeling, remain dormant.

Lead author Dayu Pan from Johns Hopkins explains, “Senescence promotes age-related musculoskeletal diseases such as osteoporosis, and removing senescent cells from degenerated vertebral disks restores the intervertebral disk structure.” The study aimed to investigate whether specific senescent osteoclasts were causing the porous endplates between vertebrae and disks, allowing nerve infiltration leading to lower back pain, and if eliminating these osteoclasts could alleviate the pain.

Targeting Senescent Osteoclasts with Navitoclax in a Mouse Model

Using a mouse model, the scientists investigated the presence of senescent osteoclasts in the porous endplates of mice experiencing two types of pain – one related to aging and the other resulting from lumbar spine instability. Once identified, they administered Navitoclax to target and eliminate these senescent cells from the affected area, resulting in reduced pain and increased activity in both groups of mice compared to a control group.

Examination of bone tissue revealed diminished degeneration and porousness in the endplates, along with reduced separation between them. Additionally, the absence of senescent cells prevented the growth of new nerves into the bones, preventing sensitivity and pain.

This outcome holds promise for the researchers, who aspire to subject it to further evaluation in a clinical trial. The study is currently available as a peer-reviewed preprint, anticipating publication in the journal eLife.

Read the original article on: New atlas

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