Osteoporosis

Osteoporotic bones are qualitatively normal but quantitatively deficient. Since these bones appear rarefied and radiolucent on radiograms, the term 'osteopenia' is often used to refer to 'poverty' of bone (Hall and Lenchik 1999; Griscom and Jaramillo 2000). Radiolucent bones, however, are not seen exclusively in osteoporosis, but also in osteomalacia, hyperparathyroidism, neoplasms, and several other conditions of varying pathogenesis (Resnick and Ni-wayama 1995). Thus, the term 'osteopenia' is not specific for, and cannot be used synonymously with, osteoporosis. Additional radiographic features may help in identification of the specific cause of osteopenia: for example, subperiosteal resorption characteristically occurs in hyperparathyroidism, while multiple focal radiolucent bone areas may suggest plasma cell myeloma. In osteomalacia the bone matrix is normal but its mineralization is defective, resulting in the 'osteopenic' appearance on radiograms. Again, supplementary radiographic signs, including Loos-er's lines, pseudofractures, and such deformities as acetabular protrusion or a bell-shaped thorax, are necessary to identify osteomalacia. In the absence of these signs, the differential diagnosis against osteoporosis can be difficult, which is why a 'hedge' word like osteopenia is used. Unfortunately, specific radiographic features are often lacking in isolated osteoporosis, which cannot be reliably diagnosed except in the presence of typical clinical and histological features (Resnick and Niwayama 1995).

Osteoporosis occurs when bone resorption exceeds bone formation, a situation that can be produced by a net decrease in bone formation, a net increase in bone resorption, or a combination of the two. Scurvy and osteogenesis imperfecta are remarkable examples of osteoporosis caused by impaired bone formation and mineralization, while hyper-parathyroidism is an example of osteoporosis caused by increased bone resorption. In normal individuals, loss of the bone mass is an age-related event that is more prominent in women than in men. Osteoporosis is established when bone loss is greater than expected for a person of a given age, sex, and race (pre-clinical state) or when it results in structural bone deficiency manifested by fractures. Several classification systems for postnatal osteoporosis have been developed. Osteoporosis has been classified as low-turnover and high-turnover types, depending on whether bone remodeling activity is decreased (steroid therapy, hepatic disease, hypothyroidism, systemic disease, malnutrition, parenteral nutrition, certain forms of postmenopausal and senile osteoporosis) or increased (anticonvulsant therapy, calcium deficiency states, gastrointestinal disease, hemo-chromatosis, hyperparathyroidism, hyperthyroidism, juvenile osteoporosis, mastocytosis, and certain other forms of postmenopausal and senile osteoporosis). Another classification system, which is taken as a reference in the following discussion, distinguishes between a generalized (most of the skeleton involved), a regional (one segment of the skeleton involved), and a localized (focal areas of osteoporosis within a skeletal segment) form of osteoporosis (Resnick and Niwayama 1995).

In generalized osteoporosis, involvement is most prominent in the axial skeleton (spine, pelvis, ribs and sternum) and proximal portions of the long bones of the appendicular skeleton. Involvement of the cranial vault is generally mild, with the exception of hyperthyroidism and Cushing disease where it can be extensive. Senile and postmenopausal osteoporosis (OMIM 166710) are the most common causes of generalized osteoporosis. Radiographic signs of axial osteoporosis, including osteopenia and vertebral collapse, have been detected in about 30% of women and 20 % of men between the ages of 45 and 95 years (Targovnik 1977). Fractures at other sites, especially in the proximal femur and distal radius, are common. The male-to-female distribution of osteoporosis is about 1:4 before the age of 80 years and tends to approach 1:1 after this age (Dunn 1967). In women after the menopause, the magnitude of cancellous bone loss with relative sparing of cortical bone is greater than in the premenopausal age, probably accounting for the increased incidence of vertebral collapse in postmenopausal women (Mazess 1982; Riggs et al. 1982; Firooznia et al. 1986a,b).Whether or not a fracture occurs in an osteoporotic patient depends upon a variety of factors. However, the single most important determinant is a decrease in bone mineral density to under a critical threshold (Genant et al. 1989). Moreover, the bone mineral density achieved during early adulthood is a major determinant of the overall risk of the development of osteoporosis in later years. Although the pathogenesis of senile and postmeno-pausal osteoporosis is unclear, different mechanisms are probably implicated. Bone formation, which seems to be preserved in postmenopausal osteoporosis (Carbonare et al. 2001; Lafferty and Fiske 1994), is likely to be deficient in senile osteoporosis, possibly as a result of impaired osteoblast function or recruitment (Jackson and Kleerekoper 1990; Rosenberg 1991). Increased bone resorption resulting from estrogen deficiency has been implicated in osteoporosis after the menopause, whether physiological or surgical (Jowsey 1966; Aloia et al. 1983). Despite the unequivocal contribution of hormonal factors to the process of osteoporosis, as supported by its occurrence in young oophorectomized women (Genant et al. 1982,2000; Dalen et al. 1974) and in hereditary gonadal dysgenesis syndromes (Elliott et al. 1959), it is possible that both postmenopausal and senile osteoporosis are involutional processes in which the diminished production of organic matrix has an essential role (Resnick and Niwayama 1995). There is compelling evidence implicating genetic factors (Seeman et al. 1989; Armamento-Villareal et al. 1992; Prockop 1998). Bone mass is lower in women than in men, and in Caucasians than in African Americans. Bone mineral density is a complex trait probably influenced by multiple genes, each with partial effects (Devoto et al. 1998). Up to 80% of the variance in bone mineral density is thought to be related to heritable factors. Defects in type I collagen similar to those encountered in osteogenesis imperfecta may give rise to a phenotype suggesting involutional osteoporosis. Polymorphisms in the type I collagen (COL1A1) gene, the type II collagen (COL1A2) gene, the estrogen receptor (ESR1) gene, the vitamin D receptor (VDR) gene, the calcitonin receptor (CALCR) gene, and the interleukin-6 gene have been correlated with decreased bone mineral density and the risk of os-teoporotic fractures (Grant et al. 1996; Uitterlinden et al. 1998; Becherini et al. 2000; Masi et al. 1998; Taboulet et al. 1998). Generalized osteoporosis can occur in association with a number of inherited or acquired disorders, including hyperparathyroidism (Perez and Pazianos 2001), hyperthyroidism (Ober-mayer-Pietsch et al. 2000; Liote and Orcel 2000), acromegaly (Bell and Bartter 1967; Longobardi et al. 1998), steroid therapy (van den Bergh et al. 2001; Kirchgatterer et al. 2000), heparin therapy (Javier et al. 1999), alcoholism (Dalen and Feldreich 1974), plasma cell myeloma (Bolzonella et al. 1984), nutritional deficiencies (Chase et al. 1980; Coin et al. 2000), diabetes mellitus (Campos Pastor et al. 2000), chronic liver disease (Heathcote 1999; McCaughan and Feller 1994), prolonged immobilization (Dalen and Olsson 1974), immunodeficiency states (Kirchner et al. 1985; Paton et al. 1997), Gaucher's disease (Katz et al. 1987), and glycogen storage disease (Lee et al. 1995).

Scurvy, a metabolic disorder caused by long-term deficiency of dietary vitamin C (ascorbic acid),man-ifests in infants and children (infantile scurvy) with characteristic skeletal changes related to impaired osteoblastic and osteoclastic cellular function, with preserved noncellular activities, including calcium deposition. The skeletal alterations are most prominent at the end of tubular bones and at costochon-dral junctions; they include a transverse band of diminished density on the metaphyseal side of provisional zone of calcification (the 'scurvy' line) and thickening and sclerosis of its epiphyseal side. Despite heavy calcification, the provisional zone of calcification is brittle and often presents subepiphyseal clefts and fractures. Small beaklike marginal outgrowths of the metaphyses and periosteal elevation with new bone formation due to subperiosteal hemorrhage are also typical (Fig. 9.1 a,b). Similar changes in the epiphyses produce a radiodense shell around the ossification center (thickening of provisional zone), with central rarefaction owing to atrophy of spongiosa. In the diaphyses, generalized atrophy of the cortex and spongiosa produces a radiolucent or "ground glass" appearance. Subperiosteal hemorrhage and periosteal elevation can be striking and are usually most frequent in the large tubular bones, such as the femur, tibia, and humerus. The adult form of scurvy can be observed in severely malnourished persons, especially the elderly, and is marked by the hemorrhagic manifestations, with hemarthrosis, bleeding at synchondroses, and skin petechiae and ecchymoses (Bevelaque et al. 1976; Haslock 2002). Osteoporosis is prominent in the axial skeleton, especially the spine, and in the tubular bones of the appendicular skeleton.

Several bone dysplasias and syndromes exhibit osteoporosis on a generalized basis. A reduced bony

Bone Dysplasia Pictures

Fig. 9.1 a, b. Scurvy in a female newborn. a Anteroposterior and b lateral projection of the left femur, showing the classic features of scurvy: osteoporosis, a sclerotic metaphyseal line with a radiolucent line ('scurvy line') below it, metaphyseal irregularities, and subperiosteal hemorrhage with periostitis. (From Dammeier et al. 1999)

Fig. 9.1 a, b. Scurvy in a female newborn. a Anteroposterior and b lateral projection of the left femur, showing the classic features of scurvy: osteoporosis, a sclerotic metaphyseal line with a radiolucent line ('scurvy line') below it, metaphyseal irregularities, and subperiosteal hemorrhage with periostitis. (From Dammeier et al. 1999)

Scruvy Radiolucent Line

Fig. 9.2. Bruck syndrome in a 5.5-month-old baby girl. Note healing diaphyseal fracture at the mid-diaphysis of radius and ulna, prominent osteoporosis, and flexion contraction of the elbow due to mild pterygia. Fixed contractures were also found at several other joint locations, including the fingers, hip, knee, and feet (not shown). (From Leroy et al. 1998)

Fig. 9.2. Bruck syndrome in a 5.5-month-old baby girl. Note healing diaphyseal fracture at the mid-diaphysis of radius and ulna, prominent osteoporosis, and flexion contraction of the elbow due to mild pterygia. Fixed contractures were also found at several other joint locations, including the fingers, hip, knee, and feet (not shown). (From Leroy et al. 1998)

mass may result from an inherent bone defect, with deficient production of woven bone and deficient mineralization, or to decreased in-utero mobility. In patients with all types of osteogenesis imperfecta (OMIM 166210, 166200, 259420, 166220, 166240, 166260), osteoporosis results from defective synthesis of collagen matrix, coupled with deficient mineralization of the matrix. The degree of osteoporosis is highly variable, ranging from bones with a normal appearance on standard radiograms to severe osteo-penia with multiple fractures. Decrease in osseous density involves equally the axial and the appendicular skeleton (McKusick 1972). Cole-Carpenter dysplasia (OMIM 112240) is a disorder similar to osteogen-esis imperfecta in which multiple fractures and bone deformities occur in association with orbital hypo-plasia and ocular proptosis, hydrocephalus, and distinctive facial features (Cole and Carpenter 1987). Osteopenia, pathologic fractures, discolored teeth, blue sclerae, and easy skin bruising suggest a connective tissue disorder, but type I collagen is normal (MacDermot et al. 1995; Amor et al. 2000). The features of Bruck syndrome (osteogenesis imperfecta with congenital joint contractures, OMIM 259450) include those of osteogenesis imperfecta plus symmetrical contractures of the knees, ankles, and feet that are reminiscent of arthrogryposis multiplex congenita (Fig. 9.2) (Viljoen et al. 1989). The bones are osteoporotic and fragile, and multiple fractures resulting in long bone deformities occur following trivial trauma. Vertebral collapses can produce spinal malalignment. Wormian skull bones are additional findings, while blue sclerae, dentinogenesis imperfecta, clubfeet, and pterygia are sometimes but not uniformly present (Sharma and Anand 1964; Brenner et al. 1993). The collagen abnormality in Bruck syndrome is different from that occurring in osteogene-sis imperfecta, being related to deficiency of bone-specific telopeptide lysyl hydroxylase resulting in aberrant crosslinking of bone collagen (Bank et al. 1999). The defect, caused by mutation at chromosome location 17p12, is unique to bones, cartilage and ligaments showing unaltered telopeptide hydroxylation and normal crosslinking. Singleton-Merten syndrome (OMIM 182250) is an early lethal, autosomal recessive condition characterized by dental dysplasia, progressive aorta calcification, aortic stenosis, generalized osteoporosis, and expansion of the marrow cavities in metacarpals and phalanges. Generalized muscle weakness and atrophy may also be observed (Singleton and Merten 1973; Gay and Kuhn 1976). In geroder-ma osteodysplastica hereditaria (OMIM 231070), an autosomal recessive condition of premature aging, osteoporosis, and susceptibility to fractures are cardinal features (Bamatter et al. 1950). The bones show multiple lines like the growth rings of trees. The skin is lax, although it is not hyperelastic as it is in the Ehlers-Danlos syndromes. The face has been described as peculiar, with a "droopy, jowled, prematurely aged appearance" (Hunter et al. 1978). This condition is phenotypically similar to the progeroid syndrome of De Barsy (OMIM 219150) and cutis laxa with bone dystrophy (OMIM 219200). A peculiar type of generalized osteoporosis due to excessive bone resorption is that seen in prepubertal children and referred to as idiopathic juvenile osteoporosis (OMIM 259750) (Teotia et al. 1979). This is a self-limiting condition characterized by axial osteoporosis, sometimes combined with vertebral collapse resulting in spinal kyphosis. The appendicular skeleton can also be affected, with thin cortices and fracture lines along the shafts of the tubular bones or, most typically, at the metaphyses of the knees and ankles (Resnick and Ni-wayama 1995). The differential diagnosis against osteogenesis imperfecta tarda can be difficult, although the metaphyseal changes described can help in the identification of idiopathic juvenile osteoporosis (Krassas 2000; Smith 1995). Osteoporosis pseudo-glioma syndrome (OMIM 259770) is an autosomal recessive disorder (gene map locus at 11q12-q13) (Gong et al. 1996) due to mutation of LDL receptor-related protein 5 (LRP5) (Gong et al. 2001) and characterized by diffuse osteoporosis starting in childhood. It is possible that this recessive gene is clinically expressed in heterozygotes (Superti-Furga et al. 1986). Affected children show musculoskeletal (osteoporosis, wormi-an bones, platyspondyly, bowing deformity of long bones, vertebral collapse, multiple fractures, muscular hypotonia, joint hypermobility) and ocular (mi-crophthalmos, vitreoretinal abnormalities, cataracts, iris and lens abnormalities, ocular calcifications) abnormalities (Bianchine et al. 1972; Briard and Frezal 1976). Differentiation from osteogenesis imperfecta is possible by means of biopsy examination of the iliac crest (McDowell and Moore 1992). Interestingly, two additional mendelian disorders involving changes in the bone mineral density have been linked to 11q12-q13: osteopetrosis, infantile type (OMIM 259700) and a disorder with isolated increase in bone mass (OMIM 601884) in the absence of other clinical features or sequelae (Johnson et al. 1997). It may be that the same chromosomal region, 11q12-q13, has a key role in the development of osteoporosis in the general population (Koller et al. 1998).

Regional osteoporosis is seen most commonly in association with limb immobilization or disuse from any cause, including fractures, amputation, motor paralysis, and bone or joint inflammation. Osteoporosis of immobilized individuals is associated with increased bone resorption (Akeson et al. 1987), as evidenced by increased urinary and fecal calcium excretion. Hypercalciuria can lead to renal calculi (Clouston and Lloyd 1987). A more diffuse pattern of bone involvement, which is somewhat reminiscent of senile osteoporosis, is observed in individuals who are totally paralyzed. However, the predominant involvement of the appendicular skeleton with relative sparing of the axial skeleton clearly differentiates these cases from those of generalized osteoporosis of the elderly. In regional osteoporosis the radiographic appearance is usually one of uniformly diminished cortical and trabecular bone. Round or bandlike areas of radiolucency in the periarticular or subchondral regions of the involved skeletal segment are less common findings (Jones 1969). Insufficiency fractures are frequent complications. Regional osteoporosis is a typical feature of reflex sympathetic dystrophy (OMIM 604335), a condition occurring in association with a number of pathologic conditions, notably trauma, myocardial infarction, stroke, degenerative cervical spine disease and disc herniation, surgery, vasculitis, and neoplasms. Middle-aged individuals are most commonly affected, with no male or female predominance. The pathogenesis is not known, but hyperactivity of the sympathetic nervous system and local hyperemia seem to play a major part in it, which is the reason for the designation. Sympathetic fibers located in the periosteum and capable of inducing both local vasodilatation and bone resorption are likely to mediate a reflex response initiated by painful stimuli (Hohmann et al. 1986; Davis et al. 1987). Characteristic sites of involvement are the shoulder and the hand, but others, including the lower extremities and the spine, can also be involved (Franck et al. 1982). Distribution is commonly bilateral and asymmetrical in terms of the degree of involvement. Pain, swelling, tenderness, and restricted movement are common presenting symptoms. In the late stages (months after onset), trophic skin changes, such as pigmentary abnormalities, skin atrophy, and hypertrichosis, are observed (Birklein et al. 2000; van der Laan et al. 1998). Clinical symptoms can either subside or persist for years. Radiographic manifestations include soft tissue swelling and regional osteoporosis, the latter presenting with a metaphyseal, subperiosteal, intracortical, endosteal, or juxta-articular pattern of bone resorption (Genant et al. 1975). The designation transient regional osteoporosis refers to a self-limiting form of regional osteoporosis characterized by acute onset, peculiar involvement of the periarticular regions, and absence of any identifiable cause (Resnick and Niwayama 1995). There are two well-recognized forms of transient regional osteoporosis, one involving the hip and the other with a characteristic migratory pattern. Whether these two forms of osteoporosis represent related but distinct disorders, or different manifestations of the same disease, is not known (Rosen 1970; Corbett et al. 1977). Certainly, both forms share the same clinical picture of pain, swelling, and restriction of joint motion at the involved site, and also an identical radiographic appearance showing periarticular osteoporosis with unchanged articular joint spaces. In addition, such mechanisms as incomplete ischemic necrosis and neurogenic reflexes similar to those of reflex sympathetic dystrophy have been implicated in the pathogenesis of both forms (Resnick and Niwayama 1995; Dihlmann and Delling 1985). Uncertainty also surrounds the relationship between transient regional osteoporosis and reflex sympathetic dystrophy, as a positive history of trauma and similarities in the pattern of skeletal involvement are features common to both disorders (Resnick and Niwayama 1995). Transient osteoporosis of the hip affects young and middle-aged adults, especially pregnant women, in a strictly unilateral distribution. Interestingly, the left hip is almost always the location in women, while either hip can be involved in men. Clinical symptoms (hip pain, limp, limitation of joint motion) usually subside within a few months without sequelae. Occa-sionally,femoral neck fracture may be a complication. Radiographic manifestations, with osteoporosis involving the femoral head (Fig. 9.3 a, b) and, to a lesser extent, the acetabulum, usually become apparent several weeks after symptom onset. Familial cases have been described (Albert and Ott 1983). In regional migratory osteoporosis the knee, ankle, and foot are most commonly involved, while the hip and the spine are usually spared (Duncan et al. 1969; Mavichak et al. 1986; Banas et al. 1990). Men are affected more frequently than women. A migratory unpredictable pattern of joint involvement is typical, with clinical exacerbations alternating with periods of quiescence.

Localized osteoporosis accompanies various focal lesions of the skeleton, including arthritis, infections, and several neoplasms. A discussion of these entities is beyond the scope of this book.

Regional Migratory Osteoporosis

Fig. 9.3 a,b. Transient osteoporosis of the hip in a 33-year-old pregnant woman with a 2-month history of left hip pain. a Note circumscribed area of decreased radiodensity in the superolateral portion of the femoral head (arrowheads), with normally preserved joint space. b At the 8-month radiographic follow-up, the osteoporotic area is no longer visible. (From Yamamoto et al. 1999)

Fig. 9.3 a,b. Transient osteoporosis of the hip in a 33-year-old pregnant woman with a 2-month history of left hip pain. a Note circumscribed area of decreased radiodensity in the superolateral portion of the femoral head (arrowheads), with normally preserved joint space. b At the 8-month radiographic follow-up, the osteoporotic area is no longer visible. (From Yamamoto et al. 1999)

Was this article helpful?

0 0
Hearing Aids Inside Out

Hearing Aids Inside Out

Have you recently experienced hearing loss? Most probably you need hearing aids, but don't know much about them. To learn everything you need to know about hearing aids, read the eBook, Hearing Aids Inside Out. The book comprises 113 pages of excellent content utterly free of technical jargon, written in simple language, and in a flowing style that can easily be read and understood by all.

Get My Free Ebook


Post a comment