OPLL: Latest Insights on Posterior Longitudinal Ossification

Ossification of the posterior longitudinal ligament (OPLL) is a condition where abnormal bone growth occurs in the spinal ligament, potentially leading to nerve compression and neurological symptoms. While more common in East Asian populations, it can affect individuals worldwide. Its progression varies, with some cases remaining asymptomatic while others lead to significant impairment.

Advances in imaging have improved early detection, while new pharmacological and surgical approaches aim to manage symptoms and prevent complications.

Affected Spinal Structures

OPLL primarily affects the cervical spine but can also involve the thoracic and lumbar regions. The posterior longitudinal ligament (PLL) runs along the back of the vertebral bodies within the spinal canal, providing structural support and limiting excessive motion. When ossification occurs, this normally flexible ligament becomes rigid, reducing spinal mobility and encroaching on the spinal cord and nerve roots. The cervical spine is most commonly affected due to its greater range of motion and biomechanical stress.

As the ossified ligament expands, it can exert pressure on the spinal cord, leading to progressive myelopathy. The degree of compression depends on the extent and morphology of the ossification, classified into continuous, segmental, mixed, or localized types. Continuous OPLL spans multiple vertebral levels, creating a broad area of compression, while segmental OPLL appears as discrete ossified regions. Mixed-type combines these patterns, often leading to more severe impairment. The localized form, though less extensive, can still cause significant symptoms if it impinges on critical neural structures.

Thoracic spine involvement is less common but presents unique challenges. The narrower spinal canal in this region leaves little room for compensatory adjustments, meaning even minor ossification can result in substantial spinal cord compression, leading to spasticity, gait disturbances, and sensory deficits. Lumbar OPLL is relatively rare and typically does not cause direct spinal cord compression due to the absence of the spinal cord in this region. However, it can compress the cauda equina, leading to lower extremity weakness, numbness, and bladder dysfunction in severe cases.

Clinical Manifestations

Symptoms vary depending on location, extent, and progression of ossification. In its early stages, OPLL may be asymptomatic, often discovered incidentally on imaging. As ossification progresses and encroaches on the spinal cord and nerve roots, individuals may develop sensory disturbances, motor weakness, and impaired coordination.

Cervical OPLL frequently causes cervical myelopathy, with symptoms such as numbness or tingling in the hands, loss of dexterity, and difficulty with fine motor tasks. As spinal cord compression intensifies, symptoms can extend to the lower limbs, affecting gait and balance. Patients may develop spasticity, leading to a stiff, unsteady walking pattern and increased fall risk. Deep tendon reflexes often become exaggerated, and in advanced cases, pathological reflexes such as the Babinski sign may emerge. Some individuals report a sensation of heaviness or fatigue in their legs, which worsens with prolonged standing or walking.

Pain is another common complaint, though its presentation varies. Some experience axial neck pain due to mechanical stress, while others develop radiculopathy, characterized by sharp, shooting pain radiating into the arms, sometimes accompanied by muscle weakness or atrophy. This pain may worsen with neck extension, which further narrows the spinal canal. Thoracic OPLL can cause a band-like sensation across the chest.

Bladder and bowel dysfunction can emerge in advanced stages, particularly when cervical or thoracic involvement leads to significant spinal cord compression. Patients may experience urinary urgency, hesitancy, or incontinence. In lumbar OPLL, where the cauda equina is more commonly affected, symptoms can include saddle anesthesia, severe radicular pain, and progressive lower extremity weakness.

Radiographic Techniques

Accurate imaging is essential for diagnosing OPLL, assessing its extent, and guiding treatment. Conventional radiography remains a primary diagnostic tool, offering an initial overview of ossified lesions. Lateral cervical spine X-rays can reveal characteristic ossification patterns, particularly in the cervical region. However, plain radiographs have limitations in evaluating the depth of ossification and its impact on the spinal canal, necessitating more advanced imaging.

Computed tomography (CT) has become the gold standard for detailed evaluation due to its ability to delineate ossified structures. High-resolution CT scans with sagittal and axial reconstructions allow precise visualization of the size, shape, and continuity of ossified plaques. This is particularly important in distinguishing between different OPLL types, which have implications for disease progression and surgical planning. CT myelography, which involves injecting contrast into the subarachnoid space, can provide further insights into spinal cord compression when MRI is inconclusive.

MRI plays a complementary role by providing critical information about spinal cord involvement. Unlike CT, which is optimal for identifying ossification, MRI is essential for detecting spinal cord edema, atrophy, or signal changes that indicate myelopathy. T2-weighted images are particularly valuable, as hyperintense signals suggest chronic compression and potential neurological deterioration. The presence of intramedullary signal changes has been correlated with poorer surgical outcomes.

Pathological Mechanisms

The development of OPLL is driven by genetic, biochemical, and biomechanical factors that promote ectopic bone formation within the spinal ligament. Genetic predisposition plays a significant role, with studies identifying familial clustering and specific genetic variants associated with increased susceptibility. Genome-wide association analyses have linked certain single nucleotide polymorphisms (SNPs) in genes related to bone metabolism, such as COL6A1 and BMP4, to an elevated risk of OPLL. These genetic influences create a predisposed environment where external triggers, such as repetitive mechanical stress and systemic metabolic disturbances, further drive ossification.

At the cellular level, fibroblasts and ligamentous cells within the PLL undergo abnormal differentiation into osteoblast-like cells, mediated by dysregulated signaling pathways. The transforming growth factor-beta (TGF-β) and bone morphogenetic protein (BMP) families are particularly implicated, as they enhance osteogenic differentiation and extracellular matrix mineralization. Elevated levels of TGF-β1 have been observed in affected ligament tissues, promoting collagen deposition and subsequent calcification. Similarly, increased BMP activity accelerates the transition from fibrocartilage to bone-like structures, reinforcing the progressive stiffening of the ligament. These molecular changes are accompanied by an upregulation of osteopontin and osteocalcin, key markers of bone formation.

Pharmacological Methods

While no medication halts or reverses OPLL, pharmacological approaches focus on managing symptoms and minimizing complications. Targeted therapies aim to alleviate pain, reduce inflammation, and slow disease progression by modulating bone metabolism.

Nonsteroidal anti-inflammatory drugs (NSAIDs) help relieve pain associated with nerve root compression and mechanical stress. For neuropathic pain, medications such as gabapentin and pregabalin modulate calcium channels to reduce aberrant nerve signaling. Corticosteroids, either orally or via epidural injection, are occasionally used for acute inflammation or radiculopathy, though their long-term efficacy is unclear.

Bisphosphonates and selective estrogen receptor modulators (SERMs) have been investigated for their potential to modulate aberrant bone formation, but clinical studies have yet to establish their definitive role. Experimental agents targeting BMP and TGF-β pathways are under investigation, with early findings suggesting they may help regulate pathological ossification, though they are not yet part of standard practice.

Surgical Methods

When OPLL leads to significant spinal cord compression or progressive neurological decline, surgical intervention is necessary. The choice of technique depends on severity, location, and morphology of the ossification, as well as the patient’s overall health. Surgical strategies fall into two categories: anterior and posterior decompression approaches.

Anterior decompression procedures, such as anterior cervical corpectomy and fusion (ACCF), directly remove the ossified ligament and affected vertebral bodies. This approach is particularly effective for localized or segmental OPLL. However, anterior surgery is technically demanding and carries risks, including graft failure, dysphagia, and dural tears. If the ossification adheres tightly to the dura, attempting resection can result in cerebrospinal fluid leaks.

Posterior decompression techniques, such as laminoplasty and laminectomy, create additional space for the spinal cord without removing the ossified ligament. Laminoplasty is favored for multilevel OPLL as it preserves spinal stability while reducing compression. By hinging the lamina open, this approach minimizes the risk of postoperative kyphosis, a concern with laminectomy, which involves complete lamina removal and may require fusion for structural integrity. While posterior approaches are generally safer, they may be less effective in cases where the spinal cord remains tethered by anterior ossification. Some patients experience residual symptoms due to incomplete decompression, particularly if the spinal cord has already sustained irreversible damage.