Metabolic and Other Nondegenerative Causes of Low Back Pain

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CHAPTER 274 Metabolic and Other Nondegenerative Causes of Low Back Pain

Omar N. Syed, Christopher E. Mandigo, Michael G. Kaiser

About two thirds of adults suffer from low back pain at some point in their lives.¹^–³ Low back complaints are the primary reason for lost productivity and the second most common reason to seek medical attention.⁴ Table 274-1 shows a broad differential diagnosis for low back pain and the estimated prevalence of various disorders observed in a primary care setting. Degenerative and mechanical disorders of the lower back account for the vast majority of patients who present with low back pain.^4,⁵ In a significantly small proportion of patients, nondegenerative disease is the cause of low back pain; this includes metabolic, inflammatory, infectious, neoplastic, hematologic, and vascular causes, as well as visceral referred pain syndromes. An understanding of nondegenerative causes of low back pain is necessary for the appropriate evaluation and triage of patients. Management often requires a collaborative effort among medical specialists, pain specialists, and surgeons. Many of these topics are covered in depth elsewhere; the following serves as a concise review of these conditions as they relate to low back pain.

TABLE 274-1 Differential Diagnosis of Low Back Pain

MECHANICAL LOW BACK PAIN (97%)	NONMECHANICAL SPINAL CONDITIONS (1%)	VISCERAL DISEASE (2%)
Lumbar strain, sprain	Neoplasia	Disease of pelvic organs
Degenerative processes	Multiple myeloma	Prostatitis
Herniated disk	Metastatic carcinoma	Endometriosis
Spinal stenosis	Lymphoma and leukemia	Chronic pelvic inflammatory disease
Osteoporotic compression fracture	Spinal cord tumors	Renal disease
Spondylolisthesis	Retroperitoneal tumors	Nephrolithiasis
Congenital disease	Primary vertebral tumors	Pyelonephritis
Severe kyphosis	Infection	Perinephric abscess
Severe scoliosis	Osteomyelitis	Aortic aneurysm
Transitional vertebrae	Septic diskitis	Gastrointestinal disease
Spondylolysis	Epidural abscess	Pancreatitis
Internal disk disruption or diskogenic low back pain	Shingles	Cholecystitis
Presumed instability	Inflammatory arthritis	Penetrating ulcer
	Ankylosing spondylitis
	Psoriatic spondylitis
	Reactive arthritis
	Inflammatory bowel disease
	Scheuermann’s disease
	Paget’s disease of bone
	Osteoporosis/osteopetrosis

Data from Deyo RA, Weinstein JN. Low back pain. N Engl J Med. 2001;344:363-370.

Metabolic Bone Disease

Metabolic bone disease, which includes osteomalacia, Paget’s disease, and osteoporosis, is considered a major health threat in the United States because more than 18 million individuals have compromised bone density. Many of these patients are at increased risk for vertebral body fractures. These fractures are one of the main causes of severe debilitating back pain that results in a reduced quality of life, physical function, and survival.^6,⁷ The occurrence of a single vertebral fracture substantially increases the likelihood of future fractures and progressive kyphotic deformity.⁸ Open surgical intervention is usually reserved for patients with neurological deficits or spinal instability. However, minimally invasive procedures, such as vertebroplasty and kyphoplasty, have become integral to the management of acute vertebral fractures.^6,⁸

Osteomalacia

Osteomalacia is the failure of the bone matrix to mineralize normally.^9,¹⁰ The most frequent causes of osteomalacia are a lack of extracellular calcium and phosphate, abnormal osteoblast function, defective collagen production, and low pH at the sites of mineralization. Osteomalacia less commonly results from vitamin D deficiency, which can be caused by inadequate exposure to sunlight or by gastrointestinal disease that interrupts normal vitamin D absorption. Abnormal intestinal absorption can be caused by biliary fistula, chronic steatorrhea, sprue, or surgical resection of a large portion of the distal jejunum and ileum.^11,¹² Osteomalacia can also result from chronic renal disease, with impaired synthesis of 1,25-dihydroxycholecalciferol and the loss of calcium resorption. Phosphate-deficient diets also cause osteomalacia. Vegetarians who eliminate dairy products from their diet are susceptible to phosphate deficiency, as are patients who take large doses of aluminum hydroxide,¹³ which can block the intestinal absorption of phosphate. Other causes include systemic acidosis,¹⁴ drug side effects,^15,¹⁶ tumor toxins,¹³ and primary mineralization defects. Severe phosphate wasting is associated with certain tumors such as sclerosing hemangioma, angiosarcoma, hemangiopericytoma, and nonossifying fibroma.¹³

Osteomalacia is often asymptomatic, but as the condition advances, diffuse skeletal pain and muscle weakness can develop. Kyphotic deformities can result from vertebral body collapse. A patient with severe osteomalacia may adopt a characteristic waddling gait owing to proximal muscle weakness and low back pain.

There is an initial decrease in bone density that is indistinguishable from osteoporosis. The pathognomonic radiologic finding in osteomalacia is the pseudofracture of long bones, characterized by a radiolucent band running perpendicular to the bone surface.¹⁷ These fractures are sometimes referred to as Fraser’s zones or milkman’s fractures. As the disease progresses, compression fractures of the vertebrae may occur with little or no trauma.

Treatment of osteomalacia is directed at correcting the underlying cause of hypophosphatemia, hypocalcemia, and vitamin D deficiency with supplements or dietary modifications. Tumor-induced osteomalacia responds to surgical removal of the tumor.

Osteoporosis

Osteoporosis is defined as a skeletal disorder characterized by loss of bone mass that causes fragility, predisposing an individual to an increased risk of fracture. It can be categorized as primary or secondary. Primary osteoporosis is most often seen in postmenopausal women and older men.⁸ An estimated 20% of women suffer an osteoporotic fracture by age 65 years, and 40% of women have an osteoporotic fracture at some point during their lives.¹⁸ Vertebral, hip, and wrist fractures are the most common. The major predisposing factors are sex hormone deficiency and reduced calcium intake in the elderly.¹⁸^–²² Other risk factors include alcohol abuse, smoking, immobilization, and lack of exercise.²³ Paradoxically, women who exercise excessively and experience weight loss and amenorrhea are at risk for osteoporosis.^24,²⁵ Secondary osteoporosis is seen with the use of corticosteroids, thyroid hormone, and anticonvulsant drugs.^15,^16,²⁶^–²⁹ It is also associated with genetic disorders such as Turner’s syndrome and Klinefelter’s syndrome and can occur in children and adolescents.¹⁸

Vertebral compression fractures are one of the most common manifestations of osteoporosis, and more than 700,000 compression fractures are seen each year.³⁰ Localized back pain is often the presenting complaint, sometimes associated with pain in a radicular distribution. Progressive loss of stature results in shortening of the paraspinal musculature; therefore, prolonged active contraction of these muscles is required to maintain posture.³¹ This is a major cause of back pain in spinal osteoporosis. Weight bearing aggravates the pain, whereas offloading the spine with bed rest improves the pain. Healing of vertebral body fractures may take 4 to 8 weeks; however, subsequent vertebral fractures may occur, producing chronic pain complaints, dorsal kyphosis (i.e., widow’s hump or dowager’s hump), and loss of height.

Plain radiographs and dual-energy x-ray absorptiometry (DXA), which is used to assess bone density, are the diagnostic modalities of choice. A biconcave central compression fracture or burst fracture is usually seen in the lumbar spine, and an anterior wedge fracture is seen in the thoracic spine.³¹

Optimal treatment for osteoporosis is prevention by maximizing bone mineral density. Medical management includes supplemental calcium, vitamin D, and bisphosphonate therapy. Calcitonin and parathyroid hormone therapy have also been used. Estrogen replacement therapy is helpful but has been associated with a higher incidence of breast cancer. The risks and benefits of hormone replacement therapy are complex and are discussed in the medical literature.³²

For symptomatic fractures, conservative treatment includes pain management and physical therapy. Thoracolumbosacral orthoses and Jewett braces may help prevent further vertebral compression. Open surgical management of osteoporotic vertebral fractures is rarely employed except in cases of neurological deterioration or significant instability. The compromised bone density makes stabilization and fusion of the osteoporotic spine a difficult endeavor. Vertebral body augmentation techniques, such as kyphoplasty and vertebroplasty, are safe and effective at reducing pain.⁸ These techniques consist of injecting polymethyl methacrylate (PMMA) bone cement into the compression fracture. These interventions are often preferred because they are less invasive and can be done in an outpatient setting.

Paget’s Disease

Paget’s disease (osteitis deformans) is a focal disorder of bone metabolism characterized by uncontrolled bone reabsorption and formation caused by excessive numbers of osteoblasts and osteoclasts, leading to the development of thick but soft bone. Paget’s disease has a predilection for the lumbosacral spine. It has a heterogeneous geographic distribution, with a much higher incidence in England and Germany; it is rarely encountered in Scandinavia, Africa, the Middle East, or Asia. Nuclear inclusions, resembling virus particles, have been seen in osteoclasts, suggesting a slow virus as a possible cause of Paget’s disease.^33,³⁴

Back or radicular pain results from compression fractures or foraminal compromise. Severe focal bone pain may also occur with sarcomatous degeneration. Radiologic abnormalities range from purely osteolytic lesions to combined osteolytic and sclerotic lesions. Thickening of the vertebrae, compression fractures, and disappearing vertebrae can be encountered.³⁵ A bone scan is the most sensitive diagnostic modality to screen for Paget’s disease.

The majority of patients are asymptomatic. Serum calcium, phosphate, magnesium, and parathyroid hormone levels are normal. There are marked increases in the concentrations of alkaline phosphatase and acid phosphatase. Treatment includes calcitonin and bisphosphonate therapy.^36,³⁷ Spine surgery may be indicated for severe spinal stenosis.

Inflammatory Disorders

The generic term spondyloarthropathies refers to a broad category of diseases characterized by systemic involvement of bone, joints, ligaments, tendons, and muscles. Inflammation of the joints of the axial skeleton, sacroiliac joints, and large peripheral joints is a pathognomonic finding. Spine involvement can occur at any level; however, low back pain is a common manifestation. In most of these disorders the rheumatoid factor is absent, creating the designation seronegative spondyloarthropathies. Rheumatoid arthritis more often involves the cervical spine and is rarely considered a cause of low back pain.

Patients with spondyloarthropathies present with pain on arising in the morning that improves with activity. This pain and tenderness are most noticeable over the spine and sacroiliac joints, restricting normal motion. Laboratory tests reveal a nonspecific systemic inflammatory response. It is important for spine surgeons to recognize these inflammatory disorders because management is often nonsurgical.

Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disorder that affects primarily the axial skeleton. Inflammation, erosions, and ankylosis of joints and the points of ligamentous attachment, tendons, and joint capsules constitute the classic pathologic pattern of AS. The sacroiliac, apophyseal, and costovertebral joints are involved in the inflammatory process. The annulus and vertebral end plates are similarly affected. The effects of AS on the appendicular skeleton are similar to those of rheumatoid arthritis. Extra-articular manifestations can occur in the ocular, cardiovascular, and pulmonary systems.

Human leukocyte antigen B27 (HLA-B27), the B27 haplotype of the major histocompatibility complex, confers a strong genetic predisposition for AS. HLA-B27 is seen in up to 90% of white western European patients with AS, compared with 8% of the general population ³⁸; the prevalence of HLA-B27 among blacks in the United States is about 2%. An unknown environmental factor in genetically predisposed patients is the likely trigger for this disease.³⁹ AS is 3 to 9 times more prevalent in men than in women. AS is milder and less rapidly progressive in women. Typically, the disease begins in people 15 to 40 years of age.^38,⁴⁰

An insidious onset of low back pain and stiffness is the usual manifestation. This pain may extend from the thoracic spine to the buttocks, radiating into the legs above the knees. It is usually worse in the morning but improves with exercise. Peripheral joint complaints and nonspecific systemic manifestations of fatigue, anemia, low-grade fevers, and weight loss are often present. Neurological symptoms can occur with spinal cord or nerve root compression, and vertebral fractures are commonly seen.⁴¹

The earliest and most specific radiographic abnormalities of AS are bilateral, symmetrical erosions and sclerosis of subchondral bone in the lower portion of the sacroiliac joint. As the disease progresses, ankylosis of this joint predominates. Ossification of the anterior longitudinal ligaments of the vertebrae occurs and results in a characteristic “squaring” of the vertebral body. This is commonly coupled with calcifications of the intraspinous and supraspinous ligaments and apophyseal joints. These changes develop in a caudal-to-rostral manner and produce the characteristic “bamboo spine” appearance.

Traditional treatment of AS begins with physical therapy. Analgesics and nonsteroidal anti-inflammatory drugs are very effective means of pain relief. Recent evidence has shown that disease-modifying antirheumatic drugs, including sulfasalazine and methotrexate, may be helpful, but so far the data are inconclusive.³⁹ Additionally, corticosteroid injections and bisphosphonates can improve pain control. Recent evidence from randomized controlled studies indicates that inhibitors of tumor necrosis factor, such as etanercept, infliximab, and adalimumab, have had a profound impact on the treatment of spine pain, function, and peripheral joint disease in those with AS.³⁹

Reactive Arthritis

The term reactive arthritis generally refers to rheumatic disorders seen after an infection, as long as the pathogen was not found in the affected joint. This term also refers to the triad of urethritis, conjunctivitis, and arthritis, which is the classic description of what was formerly called Reiter’s syndrome. In 2003 leaders in the field of rheumatology agreed to expunge the term Reiter’s syndrome from the literature and replace it with reactive arthritis.⁴² This syndrome is associated with nongonococcal urethritis and enteral infections with Shigella, Salmonella, Campylobacter, and Yersinia, and it usually occurs during or shortly after these infections. The HLA-B27 antigen is present in 80% of these patients.^38,⁴⁰ The arthritic component of reactive arthritis typically includes a periarterial arthropathy that is acute, involves a few joints (often asymmetrically), and is commonly localized within the lower extremities. Axial involvement, which occurs in more than one third of patients, includes sacroiliitis and arthropathy of the lumbosacral spine. The sacroiliitis in reactive arthritis may be unilateral and asymmetric, unlike AS and inflammatory bowel disease, but it is otherwise indistinguishable. Spinal involvement, including ossification and syndesmophyte formation, occurs less often and in a more random fashion than in AS.

Genitourinary symptoms occur in 93% of patients. Iritis and conjunctivitis with pain and photophobia occur in 20%.³⁸ One third experience fever, anorexia, and fatigue. Mucocutaneous lesions are also common. The arthritis occurs 1 to 3 weeks after the initial infection, most commonly with asymmetric pain in the knees, ankles, feet, and sacroiliac joint. The sacroiliac joint is involved in 30% to 90% of these patients and accounts for most back pain.^38,⁴⁰ Nonsteroidal anti-inflammatory drugs and steroid injections are the main agents for treatment. Antibiotic therapy is often used to treat the underlying infection.⁴³

Psoriatic Arthropathy

Psoriatic arthritis occurs in 7% of patients with psoriasis and is located primarily in the hands, feet, and axial skeleton. This arthritis most often occurs in an asymmetric distribution within joints of the peripheral skeleton; however, in 20% of patients it involves the axial skeleton. Arthritis mutilans, a severe form of the disease, occurs in 5% of patients with psoriatic arthritis and causes extensive joint destruction in the hands and feet.

The uric acid concentration is elevated in 20% of patients, who may develop gout. Thirty-five percent to 60% of those with axial skeletal involvement have elevated expression of HLA-B27.^38,⁴⁰

Radiographically, osteolysis of the proximal phalanx, widening of the distal interphalangeal joint, and long-bone periosteal reactions are seen in the extremities, but the axial findings are indistinguishable from those in reactive arthritis. Sacroiliitis may be unilateral, but ossification and syndesmophyte formation of the joint are asymmetric.

Psoriasis occurs equally in men and women, with most cases occurring in temperate climates. Among all patients with psoriasis, 5% develop psoriatic arthritis, usually after the onset of skin changes. Severe skin and nail changes increase the risk of developing psoriatic arthritis but do not correlate with arthritis symptoms. Spine involvement occurs in 20% of psoriatic arthritic patients, tends to predominate in males, and has an onset later in life.^38,⁴⁰ Additionally, it more often affects the cervical spine than the lumbar spine.

The pain of psoriatic arthritis often presents in the fingers and toes. Asymptomatic decreased motion of the spine and joints can occur, as well as tenderness at the sacroiliac joints and spine.

Enteropathic Arthritis

Enteropathic arthritis is associated with the inflammatory bowel diseases Crohn’s disease and ulcerative colitis. Joint involvement may also occur with certain gastrointestinal disorders such as celiac disease or Whipple’s disease and even following intestinal bypass surgery for obesity.⁴⁴

Peripheral arthritis occurs concurrently with exacerbations of bowel disease, whereas involvement of the spine progresses independently of the bowel disease. Of all patients with enteropathic arthropathy, 5% are HLA-B27 positive, but among patients with axial skeletal involvement, this percentage increases to 50% to 75%.³⁸

Peripheral joints exhibit soft tissue swelling and effusions, without the presence of joint space narrowing and destruction on radiographic examination. The axial skeletal changes are identical to those in AS: bilateral, symmetrical sacroiliitis; ossification; and progressive syndesmophyte formation in a symmetrical fashion.

Spondyloarthropathy occurs in about 2% to 12% of patients with ulcerative colitis and Crohn’s disease.³⁸ Pain and stiffness of peripheral and axial joints that improve with ambulation are common, along with the symptoms and signs associated with the bowel disease. Symptoms usually manifest as inflammatory spine pain and alternating buttock pain or chest pain. The bony ankylosis generally moves from the lumbar spine toward the cervical spine. Ulcerations of the gastrointestinal tract, iritis, erythema nodosum, and pyoderma gangrenosum are common.

Myofascial Pain Syndrome

Myofascial pain syndrome (MPS) may be one of the most common causes of persistent musculoskeletal pain, particularly in the cervical and lumbar region. MPS is defined as a musculoskeletal pain disorder caused by one or more myofascial trigger points and their associated reflexes. Trigger points are small nodules of hypersensitivity located in rope-like bands of skeletal muscle. They are detected through palpation on examination.⁴⁵ This syndrome frequently affects the lower back and neck; it usually occurs in middle-aged patients, with a marked female preponderance. It is often misdiagnosed as fibromyalgia. Although similar, the characteristic difference is that MPS is associated with regional pain and trigger points, whereas fibromyalgia is associated with generalized pain and tender points. MPS is frequently initiated by injury or overuse. The treatment consists of injecting the trigger points with local analgesics, followed by stretching exercises of the involved muscle groups. Strengthening exercises should be avoided. Heat and massage may be beneficial.⁴⁵^–⁴⁷ Although MPS may be prevalent, there is no modality that can render a definitive diagnosis. The diagnosis is made based on the presence of major and minor clinical criteria.⁴⁵

Infection

Infectious processes involving the lumbar spine are common sources of back pain. These infections may affect the intervertebral disk, vertebral body, pedicles and laminae, and other soft tissues immediately surrounding the spine. Infections of the spine are a common reason for surgical consultation. Surgery may be necessary in the management of these patients and can range from minimally invasive techniques for biopsy and diagnosis to open surgical decompression with stabilization.

Pyogenic Infection

Pyogenic infections of the spine almost exclusively involve the vertebral body and only rarely the posterior elements of the spine. The most frequent site of infection is the lumbar spine, followed by the thoracic, cervical, and sacral bones. The usual source is hematogenous spread of an infectious process elsewhere in the body. The routes of dissemination are thought to be the arterioles within the vertebral metaphyseal region or the valveless paraspinous venous plexus (Batson’s plexus veins).⁴⁸ These infections may manifest acutely, subacutely, or chronically, depending on the virulence of the organism and the host response to the infection.

Staphylococcus aureus remains the most common organism causing pyogenic osteomyelitis of the spine. Osteomyelitis from gram-negative rods, including Escherichia coli and Proteus, is often seen with genitourinary infections. These can occur from urinary and genital tract manipulations, after spine or urologic surgery, or from adjacent local infections. Patients with sickle cell anemia may be infected with Salmonella, and intravenous drug users may be infected with Pseudomonas aeruginosa. Diabetes, prior spine surgeries, and trauma also predispose patients to pyogenic vertebral infections.

The most common symptoms include pain and tenderness exacerbated by motion and palpation. Motion may be severely limited, and a hip flexion deformity may result from psoas muscle irritation. Most patients do not appear septic, although they may have symptoms such as fever, chills, and malaise. Fever is not present in a significant proportion of patients.

Laboratory markers include C-reactive protein and erythrocyte segmentation rate, which are usually elevated. The white blood cell count may be normal, although the differential may demonstrate an elevated neutrophil count. Blood cultures are positive in only about 50% of cases.

Radiographic changes usually do not manifest for 2 to 3 weeks, with a paravertebral shadow or loss of disk space height often being the initial sign. Vertebral end plates show an increased density at approximately 12 weeks, and lytic changes in these end plates develop later, leading to vertebral destruction and collapse. Computed tomography (CT) reveals bone erosion and vertebral destruction quite early and delineates the soft tissue abnormalities at the infection site. Magnetic resonance imaging (MRI) is becoming the most sensitive and specific method of diagnosing pyogenic infections of the spine, with a sensitivity of 96%, specificity of 92%, and accuracy of 94%.⁴⁹ The administration of gadolinium demonstrates disk space enhancement early in the course of the infection. A bone scan may localize the area before radiographic evidence exists and is extremely sensitive to early inflammatory changes.

Image-guided needle biopsy (either CT or fluoroscopy) can be used in the diagnosis and treatment of spine infections and has low morbidity and mortality. Treatment includes rest, immobilization if pain is severe, and appropriate antibiotics after cultures are obtained. A 6-week course of intravenous antibiotics is a general guideline, followed by repeat imaging to assess the efficacy of treatment. Often patients can be discharged home or to a nursing facility during the treatment period. Surgical débridement should be considered for the following situations: no clinical response is seen within the first 6 weeks, neurological compromise exists or progresses, radiographic imaging demonstrates severe neural element compression or deformity, or evidence of chronic infection exists (e.g., draining sinus tract). If there is concern about instability, spinal fixation and fusion are warranted. Reports have shown that the use of spinal instrumentation and autologous bone graft in the presence of infection does not lead to a higher risk of persistent or recurrent infection.⁵⁰

Granulomatous Disease

Granulomatous infections are caused by organisms that elicit a granulomatous immune response. When granulomatous bony infection occurs, the spine is a frequent site of involvement, with the vertebral body involved most commonly. The source of the infecting organism is usually pulmonary, with hematogenous spread to the spine.

Patients with granulomatous disease present with localized back pain that is aggravated by movement. Destruction of the vertebral bodies, intervertebral disks, and ligaments leads to a progressive deformity, and inflammatory material may compress the neural elements. The radiographic appearance is similar in the majority of granulomatous spine infections.

Laboratory evaluation and medical treatment are specific for each disease. In general, the goals of management are to eradicate the infection and prevent or treat neurological deficits and spine deformity. Tissue biopsy is necessary for diagnosis; biopsies must be evaluated for appropriate cultures and also for pathologic study. Uncommon infections such as tuberculosis and fungal infections are often first identified by microscopic evaluation. Treatment is guided by the results of the cultures. However, surgery is frequently necessary. An operation may be performed to drain abscesses, débride sequestered bone and disk, decompress the spinal cord, or stabilize the spine to prevent or correct deformity.⁵¹

The most common granulomatous infection is tuberculosis. Fungal infections caused by Blastomyces dermatitidis, Cryptococcus neoformans, Coccidioides immitis, Aspergillus, and Histoplasma capsulatum, as well as bacteria of the genus Brucella, Actinomyces bovis, and Actinomyces israelii, can also lead to granulomatous disease of the spine.⁵¹

Neoplastic Disease

Neoplasms of the lumbar spine are an uncommon cause of low back pain. Neoplastic lesions may arise locally within or adjacent to the spinal column and from the metastatic spread of distant malignancies. Local lesions consist of primary tumors of bone, spinal cord, nerve roots, meninges, and adjacent soft tissues. Metastatic lesions may arise from almost all types of malignancies; however, breast carcinoma, pulmonary carcinoma, lymphoreticular malignancies, and genitourinary tract cancers are the most common primary malignancies, accounting for more than half these lesions.

Both primary bone tumors and metastatic lesions can be found in all regions of the spine and in all age groups. The vertebral column is the most common bone site for secondary malignancy, and up to 90,000 new cases of metastatic disease to the spine are diagnosed each year in the United States alone. By contrast, primary bone tumors are rare and account for a very small percentage of spine tumors, with a prevalence of 2.5 to 8.5 cases per 100,000 persons per year.⁵² A variety of extradural and intradural soft tissue tumors may also give rise to low back pain.

Focal pain is the most common symptom in tumors of the spine, although radicular symptoms may also be present. The pain is progressive, unremitting, and usually worse at night. Compression fractures are often associated with osteolytic lesions, which may lead to instability and deformity of the spine. This may also progress to weakness in the lower limbs, sensory loss, and loss of sphincter control. Although bowel and bladder dysfunction may be seen at the initial presentation, they are almost never isolated findings.⁵³^–⁵⁵

The rate of symptom progression, the patient’s age, and the tumor’s location are of diagnostic and prognostic significance. Rapid progression of symptoms and neurological compromise are associated with more malignant tumors. Metastatic disease of the spinal column is most common in the fifth and sixth decades, corresponding to the peak incidence of carcinoma and lymphoreticular disease. Primary tumors occurring in adulthood are more often malignant, and those in childhood are likely benign. The location of the tumor may provide a clue to its malignant nature; more aggressive tumors usually present within the vertebral body, whereas benign tumors have a predilection for the posterior elements.

In addition to the history and physical examination, the diagnostic work-up includes imaging studies, such as CT and MRI, to evaluate the bone and soft tissue involvement (Table 274-2).⁵⁶ Additionally, spinal angiography, positron emission tomography, and bone scans may be indicated to aid in diagnosis.

TABLE 274-2 Primary Bone Tumors of the Spine

Benign Primary Tumors

Osteoid Osteoma and Osteoblastoma

Osteoid osteoma and osteoblastoma are pathologically similar diseases differentiated by size. Osteoid osteomas are less than 1.5 cm in diameter, and osteoblastomas are 1.5 cm or larger.⁵⁷ These lesions are solitary and painful and cause an osteoblastic reaction in the involved bone, encountered primarily in the long bones of the lower extremities.^58,⁵⁹ In reported series of osteoma and osteoblastoma, 10% to 41% of patients have spine involvement.

The lumbar spine is most often involved, with the posterior elements acting as the predominant site of origin; the vertebral body is rarely involved. These lesions are more common in males and occur most frequently in the second and third decades of life. Nocturnal pain is the characteristic complaint, and 14% to 19% of patients exhibit dramatic improvement with aspirin and nonsteroidal anti-inflammatory drugs.⁵⁸^–⁶⁰ Some patients have associated radicular involvement. Neurological deficits are more common with the larger osteoblastoma; approximately 25% to 75% of these patients present with some form of neurological deficit, compared with 0% to 30% of patients with osteoid osteoma. Osteoblastomas tends to be more aggressive and have the capacity for malignant transformation to osteosarcoma.⁶¹

Radiographic films show an expansion of cortical bone with a dense sclerotic edge and central radiolucent nidus involving the posterior elements of the spine. CT, MRI, and technetium bone scans are the diagnostic tests of choice when plain radiography is unrevealing.

Excision of the lesion is the treatment of choice, but curettage is effective when excision is not feasible. Fusion is recommended only when stability is compromised.⁶² With complete excision, pain is eliminated in 92% of patients.⁵⁹ Persistence of pain postoperatively is suggestive of residual tumor.

Osteochondroma

Osteochondromas are common benign bone lesions, with vertebral involvement occurring in roughly 7% of all cases. Hyaline cartilage–capped bony growths extend from the growth plate as solitary or multiple lesions that usually grow quite slowly. They typically involve the posterior elements, and the majority are identified in the cervical spine, particularly at C2. These lesions are also seen in patients with hereditary multiple exostoses. This condition is associated with a higher rate of malignant transformation (3% to 5%), as opposed to a 1% transformation incidence observed with solitary lesions.⁶³

These lesions are usually asymptomatic, but neurological deficits can occur if there is compression of the spinal cord or roots. Radiographic examination reveals the bony portion of the lesion, but the cartilaginous cap is rarely visualized on plain radiography. CT, MRI, and myelography may be required for complete visualization. The pathologic and radiologic hallmark of osteochondroma is continuity of the lesion with the marrow and cortex of the underlying bone.⁵⁶

Surgical excision is the treatment of choice. Recurrence is uncommon and is usually delayed if it does occur.

Aneurysmal Bone Cyst

Aneurysmal bone cysts are benign neoplastic lesions of bone consisting of anastomosis of cavernous spaces; they constitute approximately 15% of all primary spine tumors.⁶⁴ The lumbar spine is the most frequent site, followed by the thoracic spine, with cysts typically involving the posterior elements. Most lesions appear in children and young adults and are more common in women.

Pain, tenderness, and local swelling are the most common symptoms at initial presentation. As the lesion expands, spinal cord and root compression may occur.

Radiographically, these lesions often extend between multiple adjacent vertebrae. The expansive osteolytic capita with their thin cortices have a bubbly appearance that gives the lesion its name. In addition to CT and MRI, a preoperative angiogram may identify feeding vessels that can be embolized. Selective arterial embolization can reduce the vascularity of the lesion and possibly decrease intraoperative blood loss. If no feeding vessel is identified, direct percutanous embolization may be a viable option.^64,⁶⁵

The treatment of choice is en bloc excision when feasible, but curettage seems to be similarly efficacious.⁶⁴ Cysts recur in approximately 10% to 15% of cases, but a second resection or curettage is quite effective. Depending on the destructive nature of the lesion, a postoperative stabilization procedure may be indicated.

Hemangioma

Hemangioma, the most common primary tumor of the spine, usually develops in the thoracic spine. These benign tumors of vascular origin occur most commonly around the fifth decade of life and affect women slightly more frequently than men.

Hemangiomas are rarely symptomatic but can produce focal pain. Neurological symptoms may be produced by pathologic fracture, deformity development, or soft tissue extension and compression of neurological structures.

Radiographically, the vertebral body appears to have decreased density, with prominent vertical striations or “honeycombing” throughout the body. CT shows a classic “starburst” appearance.

These radiosensitive tumors can sometimes be cured by low-dose irradiation, around 30 to 40 Gy.⁶⁶ Surgical resection should be considered in symptomatic cases when irradiation is not feasible or in the presence of neurological deterioration. These tumors are often very vascular, and surgery can be complicated by significant blood loss. Endovascular intervention can facilitate surgical resection by eliminating the arterial tumor supply and dramatically reduce intraoperative bleeding.^67,⁶⁸ Other modalities, including vertebroplasty and ethanol injection, have been reported for pain relief but are usually secondary to selective angiography, surgery, and radiation.⁶⁹

Eosinophilic Granuloma

Eosinophilic granuloma is a benign lesion that is one of the reticuloendothelial proliferative diseases. Called Langerhans histiocytosis or histiocytosis X, eosinophilic granuloma has an uncertain origin. When the spine is affected, these lesions are generally found in the vertebral body, typically in a single cervical vertebra; lumbar involvement occurs much less often. Eosinophilic granulomas can occur in all age groups, but it predominantly affects children, adolescents, and young adults.⁷⁰

Pain, focal spasm, and vertebral deformity are common at presentation. As the lesion expands, bony destruction may lead to partial vertebral collapse. Complete collapse leads to the classic vertebra plana. Bony destruction is believed to be the cause of the initial signs and symptoms and the source of later neurological compression and malfunction.

Radiographically, a central lytic lesion with poorly defined margins and a periosteal reaction occurs during the initial stage of the disease. The intervertebral disk is often spared, even with complete vertebral body collapse.

Eosinophilic granuloma is usually self-limited, and many patients do not require treatment. A percutaneous biopsy can be performed, particularly when it is necessary to differentiate the lesion from other neoplasms. These lesions show evidence of spontaneous resolution by fibrosis within 1 to 2 years. When neurological compromise occurs, the combination of steroids and low-dose radiation therapy with immobilization is a widely accepted treatment. Curettage and excision may be another curative option.⁷¹

Giant Cell Tumor

Giant cell tumors of bone (osteoclastoma) are benign lesions made up of mononuclear cells interposed with multinucleated osteoclast-like giant cells. Although histologically benign, these lesions tend to be locally aggressive. Spine involvement occurs in 2% to 3% of patients with these lesions and occurs predominantly in the sacrum.^72,⁷³ Almost all lesions involve the vertebral body, but the posterior elements can also be involved. Women are affected slightly more frequently than men, with a peak incidence in the third decade. Metastasis to the lungs is possible and often portends a worse prognosis.⁷⁴

Paraspinous muscle spasm is the most common presenting symptom. Pain and radicular changes are less common. If there is sacral involvement, bowel or bladder symptoms may be clinically evident.⁷⁴

A lytic lesion that is well circumscribed or expansive, depending on the aggressiveness of the lesion, can be seen on plain radiography. A well-defined pseudocapsular margin is visible on CT, which allows complete tumor delineation. MRI reveals a heterogeneously enhancing lesion with paraspinal and epidural disease. Hemorrhage and compression fractures may be associated. Diagnosis is usually achieved with CT-guided core biopsy. Although this core needle biopsy technique may be susceptible to sampling error, a recent study recommends fine-needle aspiration biopsy and reports a diagnostic accuracy of greater than 94%.^74,⁷⁵

Because of the locally aggressive nature of these lesions, complete en bloc excision is the treatment of choice; however, local recurrence is commonly observed at 3 years after surgery.⁷⁶ Phenol injections, cement, cryosurgery, curettage, and radiotherapy may all play a role as alternatives to en bloc resection.

Malignant Primary Tumors

Multiple Myeloma and Plasmacytoma

Multiple myeloma is a monoclonal proliferation of malignant plasma cells of bone marrow that can spread throughout the body. The marrow of the spine is affected in about two thirds of patients, and the thoracic and lumbar regions are most commonly involved.⁵⁶ Multiple myeloma is rare, occurring in 4.7 of 100,000 white men and 3.2 of 100,000 white women; the frequency is twice that among blacks. In most cases the disease appears after the sixth decade, with a male preponderance in both races.⁷⁷ Plasmacytoma represents the solitary form of the disease. Plasmacytoma may occur as a lesion outside the bone marrow (extramedullary plasmacytoma) or as a solitary lesion of bone (solitary plasmacytoma). The prognosis for patients with extramedullary plasmacytoma appears to be better than that for patients presenting with multiple myeloma or solitary bone plasmacytoma.⁷⁸ Overt multiple myeloma ultimately develops in 50% to 60% of patients with solitary plasmacytoma of the bone. In one series, two thirds of patients who progressed did so within 3 years or less. In a study done at the Mayo Clinic in a cohort of 46 patients, 77% of those who progressed did so within 4 years, although progression occurred as late as 13 years.⁷⁹^–⁸¹ The spine is the initial presenting site in 25% to 50% of cases of solitary plasmacytoma. These tumors usually appear after the fifth decade of life and are 3 times more common in men than women. The thoracic spine is the most common site of involvement, but the lumbar spine is frequently involved.

The initial presenting symptom of patients with solitary plasmacytoma is deep and persistent focal pain. Neurological involvement may result from tumor impingement on neural structures, commonly from compression fractures. The symptoms of multiple myeloma are similar to those of plasmacytoma but may be more widespread and include bone pain and anemia. Paraprotein syndromes such as coagulation disorders, serum hyperviscosity, renal disease, amyloidosis, and immunosuppression can be seen in both plasmacytoma and multiple myeloma but are more common in the latter.

Bone biopsy is essential for diagnosis and helps differentiate primary disease from metastatic tumors. Bone marrow aspirate from a separate site, such as the iliac crest, is necessary to establish a diagnosis of multiple myeloma.

Radiographically, plasmacytoma lesions are lytic and usually sharply demarcated in the spine. The lytic lesions of multiple myeloma are identical to those of isolated plasmacytoma but are more widespread and have a “punched-out,” “salt-and-pepper” appearance. Bone scans can be normal or show decreased radionuclide uptake. MRI has become the diagnostic test of choice for spine assessment; CT scans are necessary to evaluate the degree of bony destruction. Skeletal survey plain radiographs are often obtained as well.

Plasmacytoma and multiple myeloma are considered very radiosensitive and chemosensitive tumors, and these modalities are the primary treatment methods. Stereotactic radiosurgery has also been used in select patients.⁸² Surgery may be necessary to address progressive neurological deficits as well as mechanical instability as a result of osteolytic bone destruction and diffuse osteoporosis.⁸³ Kyphoplasty and vertebroplasty can be used to treat pathologic fractures and can aid in pain management.⁸⁴ Medical management has also been used effectively to reduce skeletal-related events. Bisphosphonates, corticosteroids, and antineoplastic agents can be used.

The prognosis is considerably worse in multiple myeloma than in solitary plasmacytoma. Disease-free survival is possible for patients with solitary lesions, but for those with systemic multiple myeloma, median survival is 28 months, with a 25% to 29.3% 5-year survival rate.⁷⁷ With spinal cord involvement, the prognosis is worse in both diseases.

Complete surgical resection with wide margins is the treatment of choice. However, these are often technically demanding cases and may require a multidisciplinary approach. Surgical considerations include a detailed knowledge of the anatomy, an understanding of multiple surgical exposures, and acceptance of the possibility of intentional sacrifice of the sacral roots, resulting in loss of bladder, bowel, and sexual function. Additionally, sacral reconstruction and spinopelvic stabilization are often necessary. For chordomas of the spine, either spondylectomy or intralesional extracapsular excision can be performed.⁹⁶ Inadequate tumor margin is the main factor negatively affecting the prognosis and is the cause of seeding of the tumor. The rate of local recurrence after intralesional extracapsular excision, even if followed by conventional radiation therapy, is consistently higher and earlier compared to complete resection followed by radiotherapy.⁹⁷ Although chordomas are considered radioresistant, high-dose radiation therapy may serve a palliating role in the control of pain and neurological deficits.⁹⁸ Newer therapies include intensity-modulated radiotherapy and proton therapy.⁹⁵ Chemotherapy is generally ineffective. The median 5-year survival is 66% for sacral chordomas and 50% for vertebral chordomas.⁹⁴

Chondrosarcoma

Chondrosarcoma, a rare malignant tumor of cartilaginous origin, may arise as a primary malignancy or develop from benign cartilaginous tumors after irradiation. Approximately 10% of these tumors arise in the spine, and up to 60% arise in the thoracic spine; the remainder occur in the cervical and lumbar spine. Men are affected more commonly than women, and the mean age at presentation is in the fourth decade.⁹⁹

Pain is the most common presenting symptom, with neurological compromise taking place as the tumor progresses. Swelling may result in a palpable mass.

Radiographically, these lesions appear as lytic and destructive, and an associated soft tissue mass is frequently calcified. CT and MRI can delineate the tumor’s extent. MRI may show a peripheral ring of enhancement or heterogeneous enhancement of the entire tumor.⁹⁹

Complete surgical excision is the treatment of choice. The extent of surgical resection has a significant impact on the recurrence rate.¹⁰⁰ These lesions are not sensitive to radiotherapy or chemotherapy. The median survival rate is poor, with 50% mortality between 2 and 5 years.⁹⁹

Malignant Secondary Tumors

The axial skeleton is the third most common site of metastases, after the lungs and liver. Metastases are by far the most common skeletal tumors, and the spine is the most common site of involvement. Metastases account for 70% of all tumors of the spine, and the thoracic spine is most frequently involved, followed by the lumbar and then cervical regions.² The incidence of bone metastasis has risen because of a worldwide increase in the incidence of cancer, which is largely attributed to a longer life expectancy in cancer patients.¹⁰¹ The most common metastatic tumor types are breast carcinoma, lung carcinoma, lymphoma, and prostate carcinoma.

The evaluation of a patient with metastatic tumors to the spine is similar to that in patients with primary bone tumors. The common syndrome of pain; neurological compression resulting in sensory changes, motor weakness, and bowel and bladder changes; segmental destruction; and instability is typical. Radiographically, these lesions are varied and can be classified as osteolytic, osteoblastic, or mixed. CT and MRI are the methods of choice to evaluate these pathologies.

Important considerations before deciding on treatment include the patient’s age, preoperative functional status, medical comorbidities, life expectancy, and need for tissue diagnosis. Typically, surgical intervention should be offered to patients with malignant spinal cord compression.¹⁰² Surgery is often reserved for patients with a life expectancy of at least 12 months, but it should not be withheld if it will significantly improve the patient’s quality of life. Radiotherapy is often the treatment of choice for certain spinal metastases. Tumors of the prostate and lymphoreticular system are very radiosensitive. Most breast carcinomas are sensitive, but gastrointestinal and renal tumors are resistant. The radiosensitivity of the lesions often determines management.¹⁰¹ In some cases, a histologic diagnosis may be necessary, and a biopsy of a peripheral lesion or of the spine may be indicated. As a general guideline, radiation therapy is usually indicated if pain is the presenting syndrome with no neurological deficit, or if there is a stable neurological deficit.¹⁰³ If the patient’s life expectancy is very short (<3 months) or the patient is a poor surgical candidate, radiation therapy should be considered the initial treatment alternative. Chemotherapy is also used, and its effectiveness greatly depends on the relative sensitivity of the tumor. In the acute phase of management, corticosteroids are often given to patients with new or progressive neurological deficits.