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.

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 population³⁸; 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

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