Consecutive Multilevel Vertebral Paget’s Disease
of the Lumbar Spine: Differential Diagnosis

James Paget first described Paget’s disease of bone (PDB), also known as osteitis deformans, in 1877. This condition is characterized by abnormal remodeling of bones, resulting in polyostotic or monostotic lesions, due to excessive bone formation and resorption.

While Paget’s disease of bone (PDB) ranks as the second most prevalent metabolic bone disorder in European nations, it is a comparatively uncommon condition in eastern regions, particularly in China, Japan, and other Asian countries.

Paget’s disease of bone (PDB) is rare before the age of 50 and is a condition where localized areas of high bone turnover can cause problems like bone pain, deformities, and fractures.

Due to its gradual onset, diverse clinical symptoms, and radiographic results that resemble those of skeletal metastases, primary hyperparathyroidism, osteomyelitis, or osteosarcoma, diagnosing PDB can be delayed or misidentified. As a result, individuals with PDB often fail to receive timely and effective interventions during the initial phases.

The cause of this disease is not yet fully understood, but it is thought that genetic factors and paramyxovirus infection are the two most significant factors in its potential cause. PDB typically affects multiple bones in the body, with commonly involved sites including the pelvis, spine, skull, femur, and tibia.

It most commonly affects the pelvis and spine. When PDB affects the spine, the lumbar vertebrae are the most frequently involved, followed by the thoracic and cervical vertebrae.

When a single level or nonconsecutive multilevel vertebrae is affected and there is neurologic compromise, surgical treatment is usually necessary. However, in most cases, patients are referred to surgery due to a failure to diagnose and treat the condition in its early stages or due to neglect.

Paget’s disease of the spine is typically without symptoms, but common signs can include back pain, bone deformity, and difficulty with movement. Pathological fractures and neurological compression are responsible for numbness, tingling in the feet, motor disturbances in the legs, and bladder and bowel dysfunction.

Back pain is the most common symptom in Paget’s disease of bone (PDB) and is attributed to Pagetic osteoarthritis, blood engorgement of the vertebral body, hyperactive pagetic processes, and pathological fractures.

In the advanced stage of Paget’s disease of bone (PDB), radiographic imaging reveals a distinctive “picture frame” appearance of thickened cortical and encased vertebral margins. Magnetic resonance imaging (MRI) and computed tomography (CT) scans are useful in evaluating spinal stenosis and other neurological complications.

PDB is linked with heightened bone turnover, and this can be detected through increased radionuclide uptake in the affected bone with bone scintigraphy. This method is more sensitive than radiographs for diagnosis.

As a result, it is recommended to perform skeletal scintigraphy on patients suspected of having PDB to determine the extent of the disease distribution. While serum alkaline phosphatase (SAP) is not a definitive biomarker for Paget’s disease of bone (PDB), it is related to the heightened bone turnover that is present in 85% of untreated patients.

Furthermore, untreated patients show a significant correlation between the degree of increase in serum alkaline phosphatase (SAP) and the level of disease activity, as measured by scintigraphy. Ultimately, a definite diagnosis relies on pathology.

Histopathology

Abnormal remodeling results from initially increased bone resorption that triggers bone formation, as seen in the histopathological findings. During the process of bone formation triggered by initially increased bone resorption, collagen fibers are deposited in a disorganized manner and result in the formation of a “woven” bone pattern instead of the typical lamellar bone texture. The formation of structurally disorganized new bone leads to a decrease in overall bone quality and an increase in vulnerability to fractures.

Differential Diagnosis

It can be challenging to differentiate PDB from other diseases, particularly in regions with low incidence rates. PDB may be misdiagnosed as metastatic neoplasm, hemangioma, or other conditions such as renal osteodystrophy, fibrous dysplasia, primary hyperparathyroidism, or osteosarcoma. Misdiagnosis may occur due to a family history of cancer and neglecting crucial laboratory tests and bone biopsy.

In a case reported by literature, radiographs and MRI did not show any evidence of neoplastic tissue in the vertebral body and paravertebral soft tissue. There is a lack of positive tumor biomarkers. Given this evidence, it was justifiable to rule out the possibility of a metastatic neoplasm.

The absence of the “corduroy” appearance on X-ray film and the “polka dot” pattern on axial CT scan did not support the diagnosis of hemangioma. There was no indication of hemangioma as there was no “corduroy” appearance on X-ray film and “polka dot” pattern on axial CT scan.

The possibility of hyperparathyroidism was ruled out due to normal levels of serum calcium, urinary phosphate excretion, and parathyroid hormone. Furthermore, neither the Tc-bisphosphonate scintigraphic scan nor the ultrasonic examination provided evidence of ectopic parathyroid or hyperfunctional thyroid adenoma.

Chronic renal failure is the underlying cause of renal osteodystrophy. Rephrased: Bone mineralization deficiency is a defining feature of renal osteodystrophy and is caused by an underlying metabolic disorder of calcium and phosphorus, typically associated with chronic renal failure.

Mainly affecting adolescents, fibrous dysplasia is a condition characterized by the replacement of normal bone with fibrous tissue and immature woven bone. Fibrous dysplasia is frequently observed in the limbs and skull, and it is more prevalent in adolescents. The X-ray revealed oval lesions surrounded by a thick and distinct rim of sclerosis, along with expansion and osteolysis.

The pathological fracture and collapse of the vertebral body can result from bone fibrosis. Important indicators of osteosarcoma include increasing SAP levels and the presence of paraspinal soft tissue mass. While tumor biomarkers and MRI can be helpful in ruling out spinal tumors, a definitive diagnosis ultimately depends on pathology.

A percutaneous transpedicular vertebral biopsy is required to eliminate the possibility of osteoblastic metastases, osteosarcoma, or other diseases when the diagnosis is uncertain, especially when imaging tests, such as plain radiographs combined with CT scans (MRI), are inconclusive.

Final Diagnosis

Medical treatment for PDB primarily involves the use of bisphosphonates and calcitonin, which have been clinically proven to be effective, after confirming the diagnosis and evaluating the disease activity.

Surgery is recommended when medical therapy fails, there is neurological compression due to an unstable pathological fracture or dislocation, spinal deformity, severe arthritis, or sarcomatoid transformation.

Increased intraoperative risk due to blood loss may be a concern because pagetic bone is known to have a higher number of blood vessels compared to healthy bone. Hence, it is imperative to administer bisphosphonates therapy prior to surgery. Furthermore, administering bisphosphonates therapy before surgery can be crucial for enhancing bone strength and quality before the operation, resulting in better surgical results.

Spine surgeons need to be aware of Paget’s disease with multilevel vertebral involvement as it is a rare condition. This can help prevent delayed diagnosis, unnecessary invasive examinations, misdiagnosis, and inappropriate treatment.