Gabapentin (often sold as Neurontin) is commonly prescribed to manage conditions like nerve pain, seizures, and restless legs syndrome. Because it is often used long-term, questions have arisen about its impact on skeletal health. A significant concern is whether the medication contributes to reduced bone mineral density (BMD) or an increased risk of fracture. Research is ongoing to clarify the potential risks associated with its extended use.
Current Research on Bone Mineral Density
The clinical evidence linking gabapentin use directly to reduced bone mineral density is complex and not definitively established as a direct cause. Epidemiological studies often focus on the association between gabapentin use and the risk of bone fractures. Multiple large-scale observational studies suggest an increased risk of non-traumatic fractures, particularly in patients aged 50 years and older taking gabapentin long-term.
This correlation raises the question of whether the increased fracture rate is due to weakened bones or other side effects of the drug. Gabapentin is known to cause dizziness, sedation, and impaired coordination. These factors can independently increase the risk of falls, a common cause of fractures in older populations. This makes it difficult for researchers to isolate a direct bone-weakening effect from an indirect effect related to falls.
Despite these confounding factors, some prospective studies have noted a significant loss of bone mineral density at sites like the femoral neck in elderly male patients using the medication. While not all animal studies show a change in BMD, others have demonstrated that chronic gabapentin exposure can lead to the rarefaction, or thinning, of cancellous bone structure. The relationship appears most pronounced in individuals on high-dose or long-duration therapy, suggesting a cumulative effect on the skeleton over time.
Potential Mechanisms Affecting Bone Health
The proposed biological pathway involves gabapentin’s mechanism of action, which targets the alpha-2-delta-1 auxiliary subunit of voltage-gated calcium channels in the nervous system. This same subunit is also expressed in the cells responsible for bone remodeling, suggesting a direct link to skeletal tissue.
By binding to this subunit in bone cells, gabapentin is hypothesized to disrupt the balance between bone formation and bone resorption. Studies show the drug may suppress the activity of osteoblasts, the cells responsible for building new bone tissue, leading to decreased mineralization. Simultaneously, gabapentin has been observed to enhance the activity of osteoclasts, the cells that break down old bone tissue, shifting the balance toward bone loss.
Unlike older anti-epileptic drugs that promote bone loss by inducing liver enzymes that break down Vitamin D, gabapentin is not an enzyme inducer. The drug’s interaction with the alpha-2-delta-1 subunit may indirectly lead to impaired bone mineralization through downstream effects. These effects may involve phosphate wasting or a functional deficiency of active Vitamin D, both necessary for proper calcium absorption and bone health.
Monitoring and Proactive Strategies for Patients
Given the potential for skeletal impact, individuals taking gabapentin for an extended period should proactively discuss their bone health with a physician. Monitoring is particularly important for high-risk patients, including those over 50, post-menopausal women, and those on high-dose or long-duration therapy.
For those at higher risk, a physician may recommend a Dual-Energy X-ray Absorptiometry (DEXA) scan to establish a baseline and monitor changes in BMD over time. Supporting bone health requires adequate intake of bone-supporting nutrients, specifically Calcium and Vitamin D.
The recommended daily intake of Calcium for most adults is 1,000 milligrams (mg), increasing to 1,200 mg for women aged 51+ and men aged 71+. The recommended daily intake of Vitamin D is 600 to 800 International Units (IU) for most adults, or 800 to 1,000 IU for those over 50. Since Vitamin D is necessary for Calcium absorption, supplementation may be needed, especially for those with limited sun exposure.
Incorporating weight-bearing exercise is a recommended strategy to help maintain or increase bone strength. Activities that force the body to work against gravity signal the bone to grow stronger. Examples of weight-bearing activities include:
- Walking.
- Dancing.
- Stair climbing.
- Low-impact aerobics.
Resistance training, which involves using weights or resistance bands, complements weight-bearing exercise by strengthening muscles and promoting bone density.