Drug Induced Osteoporosis

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Steroids, heparin, and methotrexate are well-known osteoporosis-inducing drugs. Of these, steroids cause osteoporosis by decreasing bone formation through the inhibition of osteoblast formation and by increasing bone resorption through either direct stimulation of osteoclasts or increasing parathormone release (Sambrook and Jones 1995). The hypercortisonism of Cushing's disease (endogenous and exogenous) also causes systemic osteoporosis. The daily administration of heparin in doses larger than 15,000 units has been reported to lead to osteoporosis in patients with myocardial infarction, thrombophlebitis, pulmonary emboli, or cerebral thrombosis (Griffith et al. 1965). A pathological study of biopsied bone from heparin-induced osteoporosis by Megard et al. (1982) demonstrated severe osteoporosis with rarefied spongy bone and increased osteoclasts and decreased osteoblasts. Unfractionated heparin causes symptomatic spinal fractures in up to 3% of patients on long-term treatment and osteopenia in 30% (Hawkins and Evans 2005). In addition, these authors reported that low molecular weight heparin reduces the risk of osteoporosis and spinal fractures. Methotrexate is another medicine that may lead to iatrogenic osteoporosis (Mazanec and Grisanti 1989). It is used for the therapy of a wide variety of diseases including breast carcinoma, acute lym-phocytic leukemia in children (Schwartz and Leonidas 1984), rheumatoid arthritis (Maenaut et al. 1997), systemic lupus erythematosus, psoriasis, and scleroderma (Singwe et al. 1998).

Women With Scleroderma

Fig. 15.16A, B Methotrexate-induced osteoporosis. A Lateral radiograph of the skull in a 50-year-old woman post-operatively treated with methotrexate for breast cancer shows diffuse porosis with white pencil-line cranial tables and washed-out sella (arrow). B Lateral pinhole scinti-graph reveals diffusely increased tracer accumulation in the cranium and skull base with the salt-and-pepper sign

Fig. 15.16A, B Methotrexate-induced osteoporosis. A Lateral radiograph of the skull in a 50-year-old woman post-operatively treated with methotrexate for breast cancer shows diffuse porosis with white pencil-line cranial tables and washed-out sella (arrow). B Lateral pinhole scinti-graph reveals diffusely increased tracer accumulation in the cranium and skull base with the salt-and-pepper sign

Osteonecrosis The Hip

Fig. 15.17A, B Steroid-induced porosis and avascular osteonecrosis. A Anteroposterior radiograph of the right hip in a 62-year-old man treated with steroids for Wegener's granuloma of the nose shows no abnormality (?). B Anterior pinhole scintigraph reveals intense tracer uptake in the femoral head with an ovoid photon defect denoting avascular necrosis (open arrow)

Fig. 15.17A, B Steroid-induced porosis and avascular osteonecrosis. A Anteroposterior radiograph of the right hip in a 62-year-old man treated with steroids for Wegener's granuloma of the nose shows no abnormality (?). B Anterior pinhole scintigraph reveals intense tracer uptake in the femoral head with an ovoid photon defect denoting avascular necrosis (open arrow)

Radiographic changes of drug-induced osteoporosis are not dissimilar to those of osteoporosis of other etiologies. Thus, the fundamental feature is generalized graying of cancellous bones with cortical accentuation. The skull presents the pencil-line sign of the thinned outer and inner tables with graying of the squamosal portions (Fig. 15.16A). The hip is one of the most common sites of steroid-induced osteoporosis and avascular osteonecro-sis, showing coarsened trabeculae (Fig. 15.17A).

Insufficiency fractures of the spine and sacrum and infractions of the ribs are other important features. Frequently, fractures and infractions are not detected because of profound osteopenia. Calluses in insufficiency fractures tend to be extensive, clearly standing out against gray bones in the background.

Scintigraphic features include a generalized increase in bone uptake, especially in young patients, with more intense tracer uptake in fractures and infractions. In the skull, drug-in-

Exogenous Cushing Syndrome
Fig. 15.18 Exogenous Cushing's disease. Posterior whole-body bone scintigraphy in a 68-year-old woman under long-term treatment with steroids for rheumatoid arthritis shows tracer uptake in the skull, facial bones, ribs, spine, and pelvis (arrows) as well as polyarthritis (arrowheads)

duced osteoporosis is indicated by markedly increased uptake in the entire cranial vault seen tangentially and by coarse granular uptake in the squamosal portion seen en face (Fig. 15.16B). Bone scanning is extremely useful for detecting avascular necrosis, which often accompanies steroid-induced osteoporosis (Fig. 15.17B). Osteonecrosis is painful, but may often pass undetected by radiography in the early stages (Fig. 15.17A). Exogenous Cushing's disease manifests as increased tracer uptake in the skull, facial bones, ribs, spine, and pelvis as well as arthropathy for which steroids are prescribed (Kingsley and Hickling 1986) (Fig. 15.18).

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