Any bone or bones can be affected, but Pagets disease occurs most frequently in the spine, skull, pelvis, femur, and lower legs. Osteogenic sarcoma, a form of bone cancer, is a rare complication of Pagets disease occurring in less than one percent of those affected. The development of osteosarcoma may be suggested by the sudden onset or worsening pain. Epidemiology
Pagets disease of bone is the second most common metabolic bone disorder, after osteoporosis. The overall prevalence and severity of Pagets disease are decreasing; the cause for these changes is unclear. Pagets disease is rare in people less than 55 years of age, and the prevalence increases with age. Evidence from studies of autopsy results have demonstrated Pagets disease in about 3 percent of people older than 40 years of age. Pagets disease is more common in males than females. Rates of Pagets disease are about 50 percent higher in men than in women. About 15 percent of people with Pagets disease also have a family member with the disease. In cases where the disease is familial, it is inherited in an autosomal dominant fashion, although not all people that inherit the affected version of the genes will express the disease (incomplete penetrance).The incidence of Pagets disease varies considerably with geographic location. Pagets predominantly affects people of European descent, whereas people of African, Asian, or Indian descent are less commonly affected. Pagets disease is less common in Switzerland and Scandinavia than in the rest of Western Europe.
Cardiotoxicity is a major problem with people treated with higher dose regimens.High-dose intravenous cyclophosphamide can cause the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a potentially fatal hyponatremia when compounded by intravenous fluids administered to prevent drug-induced cystitis. While SIADH has been described primarily with higher doses of cyclophosphamide, it can also occur with the lower doses used in the management of inflammatory disorders. Bladder bleeding
Acrolein is toxic to the bladder epithelium and can lead to hemorrhagic cystitis, which is associated with microscopic or gross hematuria and occasionally dysuria. Risks of hemorrhagic cystitis can be minimized with adequate fluid intake, avoidance of nighttime dosage and mesna (sodium 2-mercaptoethane sulfonate), a sulfhydryl donor which binds and detoxifies acrolein. Intermittent dosing of cyclophosphamide decreases cumulative drug dose, reduces bladder exposure to acrolein and has equal efficacy to daily treatment in the management of lupus nephritis. Infection
Neutropenia or lymphopenia arising secondary to cyclophosphamide usage can predispose people to a variety of bacterial, fungal and opportunistic infections. No published guidelines cover PCP prophylaxis for people with rheumatological diseases receiving immunosuppressive drugs, but some advocate its use when receiving high-dose medication. Infertility
Cyclophosphamide has been found to significantly increase the risk of premature menopause in females and of infertility in males and females, the likelihood of which increases with cumulative drug dose and increasing patient age. Such infertility is usually temporary, but can be permanent. The use of leuprorelin in women of reproductive age before administration of intermittently dosed cyclophosphamide may diminish the risks of premature menopause and infertility.