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The skeletal manifestations of metabolic disease are a heterogeneous group of conditions resulting from endocrinopathy, vitamin deficiency, renal tubular dysfunction, and disorders of endogenous metabolism. As a group, they are characterized by altered function of the osteoblasts and osteoclasts or abnormal rates of mineralization. Consequently, there are pathologic changes in the bone mass, the collagen framework of the bone, the degree of bone mineralization, and the level of osteoclastic and osteoblastic activity.
The two most common metabolic conditions affecting the spinal column are osteoporosis and renal osteodystrophy. Crystal deposition diseases typically involve the appendicular skeleton more than the spinal column. Endocrinopathies are associated with remodeling of the axial and appendicular skeleton secondary to the systemic effects of the hormonal imbalances.
Paget's disease, although not a metabolic bone disorder, is also characterized by abnormal function of osteoclasts and osteoblasts resulting in bone remodeling.
The term osteoporosis signifies decreased volume of normal bone, predisposing a person to an increased risk of fractures. Osteoporosis arises as a multifactorial disorder of bone mineral homeostasis that reduces bone mineral density, compromises bone strength, and leads to increased risk of fractures, particularly in the elderly. Osteoporosis is to be distinguished from osteopenia , which signifies reduced bone mass and osteomalacia , which signifies abnormal increase in unmineralized osteoid.
Osteoporosis affects one in four women and one in eight men older than age 50 years: 10 million individuals in the United States are affected. Both men and women experience age-dependent decline in bone mineral density (BMD) starting in midlife. However, in women bone loss occurs more rapidly right after menopause.
Primary generalized osteoporosis is classified into perimenopausal and senile osteoporosis. The two major risk factors for osteoporosis are female gender and increased age. Other significant risk factors are estrogen deficiency, late menarche, early menopause, white race, low body mass index, family history of osteoporosis, and smoking. Senile osteoporosis is seen in both males and females after age 70 years.
Secondary osteoporosis occurs in many medical conditions that interfere with bone homeostasis, including genetic, endocrine, gastrointestinal, hematologic, connective tissue disorders, and nutritional deficiencies. In males, 30% to 60% of osteoporosis is secondary osteoporosis, mainly from hypogonadism, use of glucocorticoids, or alcohol abuse.
Senile and postmenopausal osteoporosis may be asymptomatic. Back pain may be associated with loss in the height of the vertebral bodies and increased kyphosis. The weakened vertebrae may fracture after minimal trauma.
Bone mass increases throughout childhood and adolescence until the third decade of life. Adequate nutrition, exposure to sex hormones at puberty, physical activity, and individual genetic factors determine the peak bone mass attained early in life. Postmenopausal osteoporosis affects mainly the trabecular bone, leading to vertebral and wrist fractures. In senile osteoporosis both cortical and trabecular bone density are decreased. The bone is lost because the resorption associated with endogenous metabolism is not counterbalanced by normal osteoblastic activity. Sex hormones have an anabolic effect on skeletal metabolism, whereas glucocorticoid adrenocortical hormones have a catabolic action on skeletal metabolism. Metabolically, postmenopausal status and senescence are characterized by both relative hypoestrogenism and hypercortisolism, leading to bone loss.
Hyperparathyroidism causes a distinctive replacement of lamellar bone with woven bone and fibrous tissue.
The spinal column is composed predominantly of trabecular bone, so osteoporosis affects the spine early on. Macroscopically, decreased numbers of bone trabeculae are observed within normal-appearing bone marrow.
The histopathologic appearance of osteoporosis is designated “smooth bone atrophy” and is characterized by thin, sparse bone trabeculae with smooth surfaces situated within enlarged intertrabecular marrow spaces.
The diagnosis of spinal osteoporosis is based on changes in bone radiolucency, trabecular pattern, and shape of the vertebral bodies ( Fig. 16-1 ). Accentuation of the vertical trabecular pattern, resorption of horizontal trabeculae, and depression of the superior margin of the vertebral body are noted, with overall decreased number and thinning of the trabeculae. Vertebral wedging, compression fractures, biconcave deformities of the vertebral bodies (“fish-mouth vertebrae”), and Schmorl's nodes can be observed.
BMD is used to quantify bone strength. BMD corresponds to the bone mineral content divided by the area or volume of bone, depending on the technique used to measure it. A T-score is defined as the number of standard deviations above or below the average BMD value for young healthy white women. The Z-score represents the number of standard deviations above or below the average BMD value for age- and sex-matched controls. According to the World Health Organization, osteoporosis is present when the T-score is 2.5 standard deviations below the mean for young white adult women. T-scores were based originally on assessment of BMD at the hip by dual-energy x-ray absorptiometry (DEXA). However, they have been extended to include diagnostic thresholds at other skeletal sites and for other technologies, such as peripheral DEXA, quantitative CT (QCT), and quantitative ultrasonography (QUS).
MR spectroscopy and MR perfusion have been used to measure vertebral bone marrow fat content and bone marrow perfusion in elderly men. Vertebral bone marrow fat content is significantly increased in patients with osteoporosis or osteopenia compared with matched controls. Bone marrow perfusion is significantly decreased in osteoporotic patients compared with both osteopenic and normal subjects.
High-resolution bone MRI successfully displays the trabecular structure of peripheral joints. However, present MR-based quantitative measurements, such as trabecular bone volume fraction and trabecular thickness, likely overestimate trabecular volume and thickness owing to partial volume effects.
Gout is a metabolic arthropathy caused by deposition of monosodium urate crystals in the articular cartilage, subchondral bone, synovium, and capsular and periarticular soft tissues of one or more joints.
Gout typically affects the distal joints of the appendicular skeleton and rarely involves the spine. The initial attack of gout commonly occurs in the fifth decade of life in men but can occur in postmenopausal women (M:F = 20:1). The prevalence of spinal gout is not known. Patients affected by spinal gout are mostly men 33 to 76 years of age. Eighty-two percent of patients with spinal gout have chronic polyarticular tophaceous gout and hyperuricemia with a mean duration of disease of 14 years. However, spinal involvement can be the first manifestation of the disease.
Acute gouty arthritis presents as recurrent episodes of monoarticular or oligoarticular pain, tenderness, and swelling. The initial attack typically occurs in the first metatarsophalangeal joint. Chronic gouty arthritis develops in less than 50% of patients with recurrent acute gout. About 73% of patients with spinal gout have neurologic symptoms, including neck or back pain, fever, cord compression, and radiculopathies. In patients with acute or progressive myelopathy, spinal gout should be suspected when there is a past history of gout or a current history of active gouty arthritis (synovitis of the elbows, knees, and first metatarsophalangeal joints). In contrast, the correct diagnosis can be challenging when spinal involvement is the only manifestation of gout. Acute attacks are treated with nonsteroidal anti-inflammatory agents, intravenous colchicine, or systemic or intra-articular corticosteroids. Long-term management of spinal gout is with allopurinol.
In humans, the end product of purine metabolism is uric acid. Hyperuricemia can result from several metabolic abnormalities, including (1) increased activity of phosphoribosylpyrophosphate synthetase, which is involved in the conversion of purine nucleotides into uric acid; (2) deficiency of glucose-6-phosphatase; (3) deficiency of hypoxanthine-guanine phosphoribosyltransferase; and (4) renal disease with decreased tubular secretion of urate. Uric acid salts, particularly monosodium urate crystals, form in the presence of elevated concentration of uric acid. Deposition of monosodium urate crystals in the synovia produces arthritis of the peripheral joints. Chronic gouty arthritis is characterized by deposits of monosodium urate called tophi in subjects with long-standing gout or a high body load of urate. Involvement of the cervical, thoracic, and lumbar spine and the sacroiliac joint has been reported.
Macroscopically, tophi appear as chalky white material deposited in the cartilage, vertebral bodies, facet joints, and intervertebral discs.
In chronic tophaceous gout, urate deposition can occur in the articular cartilage, subchondral bone, synovium, and capsular and periarticular soft tissues. When gout is a consideration, biopsy material must be sent for pathologic analysis in 100% alcohol because formalin dissolves urate crystals. Histologic evaluation of tophaceous deposits shows a matrix containing urate crystals embedded in a chronic granulomatous stroma ( Fig. 16-2 ). Examination of the specimen with negatively polarized light reveals negatively birefringent crystals, which are diagnostic of tophaceous gout.
In spinal gout, spine radiographs can be normal or show nonspecific findings that mimic degenerative disc disease. Spinal gout may present as an erosive arthritis centered at the level of the disc, with disc space narrowing, end plate erosions (caused by urate crystal deposits), and secondary proliferative bone changes, such as hyperostosis and marginal osteophytosis ( Fig. 16-3 ). Joint subluxations, spinal deformities, pathologic fractures, and erosions of the odontoid and of the facet joints can also occur.
CT has limited utility in spinal gout. CT better delineates the erosions of the vertebral end plates and facet joints that are frequently seen in spinal gout. On CT, tophi may resemble calcifications, because monosodium urate deposits have high attenuation values (170 ± 30 HU), similar to calcium.
On MRI, the involved discs and end plates appear inhomogeneous and often show low T2 signal due to fibrous tissue and crystal deposition. The affected intervertebral discs, adjacent end plates, facet joints, posterior elements, and epidural space may show abnormal contrast enhancement due to the vascularized reactive tissue within the lesions ( Fig. 16-4 ). Gouty tophi can extend posteriorly from the intervertebral disc and end plates into the epidural space and mimic epidural abscess. However, gouty tophi have low signal intensity on T2-weighted imaging (T2W), which may help to differentiate spinal gout from discovertebral infection. Spinal gout can mimic other conditions, including epidural abscess, discovertebral infection, facet joint infection, metastases, dialysisrelated spondyloarthropathy, and calcified tumors. At the atlantoaxial joint, gout may erode the odontoid process and resemble rheumatoid arthritis. For these reasons, the imaging diagnosis of spinal gout can be challenging.
Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a disorder characterized by accumulation of CPPD crystals in or around the joints. These depositions may cause pseudogout with recurrent acute attacks of arthritis affecting one or more joints.
Calcium hydroxyapatite (HA) crystal deposition disease (HADD) is characterized by para-articular deposition of HA crystals, leading to calcification of tendons, bursae, ligaments, and peritendinous tissues.
CPPD crystal deposition disease is a common condition affecting middle-aged and elderly patients, with a slight female prevalence. Three forms of CPPD crystal deposition disease are known: sporadic, familial, and secondary (associated with other metabolic diseases such as hemochromatosis, hyperparathyroidism, hypothyroidism, and Wilson's disease). Spinal manifestations of CPPD crystal deposition disease are not uncommon and in certain cases can be the only manifestation of the disease. Japanese patients manifest spinal involvement in CPPD crystal deposition disease more commonly than do other ethnic populations.
HADD is usually monoarticular and presents between the ages of 40 and 70 years.
CPPD crystal deposition disease presents a variable clinical picture, ranging from acute arthritis to chronic progressive arthritis, with or without acute exacerbations. Pseudogout attacks can occur spontaneously or be triggered by direct trauma, medical conditions, or surgery. CPPD crystal deposition disease affects the thoracic and lumbar spines more than the cervical spine. Spinal involvement may cause no symptoms or only minimal back pain. In patients with large calcific deposits in the spine there may be an insidious myelopathy or myeloradiculopathy. The acute back pain can be accompanied by fever, joint pain, constitutional symptoms, and elevated erythrocyte sedimentation rate. Therapy for CPPD crystal deposition disease is directed at the relief of symptoms, because there is no specific medical therapy to dissolve the crystals or prevent new crystal formation.
Patients with HADD present with swelling, pain and decreased mobility of the affected joints, and occasionally fever. Treatment of HADD is symptomatic.
The pathophysiology of CPPD deposition is still unclear. CPPD crystals accumulate in the intervertebral discs, intraspinal and extraspinal ligaments, median atlantoaxial joint, facet joints, and sacroiliac joints, among other sites. Within the disc, the crystals may deposit in the annulus fibrosus, nucleus pulposus, or both. Acute and chronic CPPD deposition induces destructive lesions of vertebral bodies and discs that may be confused with infectious discitis or neuropathic disease. Facet disease can lead to destructive arthropathy and spondylolisthesis. CPPD can accumulate in the ligamentum flavum and posterior longitudinal ligament, causing myelopathy and spinal canal stenosis in very severe cases. Accumulation of CPPD crystals in the transverse and alar ligaments about the dens causes the “crowned dens syndrome” with cord comp-ression, bone erosion, fracture, and atlanto-odontoid subluxation.
HADD is thought to be secondary to deposition of HA crystals in the soft tissues either after microtrauma or secondary to a metabolic disorder. The condition becomes symptomatic when calcific deposits rupture into adjacent bursae or soft tissues. Phagocytosis of the crystals by macrophages and neutrophils then activates an inflammatory response, causing calcific periarthritis.
Grossly, the CPPD crystals appear as chalky white deposits of crystals. Spinal specimens show that disc calcifications are more common in the thoracic and lumbar spine than in the cervical spine, often involve the annulus fibrosus, and rarely involve the nucleus pulposus. The crystal deposits appear as calcifications in the facet joints, ligaments, and, in one specimen, the transverse ligament of the atlas and synovium of the atlantodental joint.
Histology shows amorphous calcifications in the context of chronic inflammatory and fibrous tissue. The CPPD crystals are rhomboid or rod shaped and are positively birefringent with polarized-light microscopy ( Fig. 16-5 ).
Plain radiographs show densities at the margins of the intervertebral disc spaces consistent with calcification of the outer fibers of the annulus fibrosus. These resemble the early syndesmophytes of ankylosing spondylitis. Disc space narrowing and significant vertebral sclerosis are additional nonspecific features of CPPD crystal deposition disease. The calcifications may not be dense enough to be detected on conventional radiographs. They may be difficult to distinguish from adjacent osteophytes in spines affected by degenerative disc and joint disease.
HADD of the spine is characterized by calcification of the longus colli muscle, in particular of the superior lateral portion of the muscle near to C2. The calcification can be accompanied by soft tissue swelling. Calcifications of the ligamentum flavum, interspinous bursae, facet joints, and infraoccipital region can also occur.
CT typically shows linear calcifications of the intervertebral discs, calcifications of the ligamenta flava and facet joints, and additional perivertebral calcific deposits ( Fig. 16-6 ). The calcifications of the ligamenta flava are usually nodular or ovoid and are contiguous with the lamina. The dura mater can also contain calcific deposits.
CPPD crystal deposits in the ligamentum flavum and discs demonstrate low T1 and T2 signal intensity. The ossified ligamenta flava appear as ovoid or nodular hypointense masses, which, if large, may compromise the spinal canal and compress the spinal cord. Tumorous deposits of CPPD crystals in the ligamenta flava may mimic bone tumors. In the cervical spine, CPPD crystal deposits may form a periodontoid mass indistinguishable from rheumatoid arthritis ( Fig. 16-6 ), compressive ossifications of the ligamenta flava below the axis, or both.