european medicines agency (ema) recommended that calcitonin be used only on a short-term basis for 3 conditions for which it had previously been approved in the european union: paget's disease, acute bone loss resulting from sudden immobilization, and hypercalcemia caused by cancer. as a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat paget's disease, the ema said. the agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer. the ema based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. conducted by the agency's committee for medicinal products for human use (chmp), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources. in 2014, the fda noted the risk imbalances in the prescribing information for miacalcin but declined to label this product with a boxed warning as a causal association was not identified. a more recent meta-analysis determined that a causal link between calcitonin and cancer is both unlikely and antithetical to known biology, although a weak association was not definitively excluded. the available studies for analysis were inconsistent and nonspecific, with one study noting an increased risk of liver cancer and decreased risk of breast cancer. this was not replicated in any other study. additionally, there is question of the overall efficacy of calcitonin-containing nasal sprays. a phase iii trial found no difference between placebo and nasal calcitonin sprays on lumbar bone mineral density in osteoporosis. it did find a significant increase in bone mineral density with oral calcitonin. this result was replicated in another study, but this study found that the bone mineral density increase did not significantly impact fracture risk. however, these studies were only inclusive of osteoporosis. surgery medical therapy prior to surgery helps to decrease bleeding and other complications. patients who are having surgery should discuss treatment with their physician. there are generally three major complications of paget's disease for which surgery may be recommended. fractures — surgery may allow fractures to heal in a better position. severe degenerative arthritis — if disability is severe and medication and physical therapy are no longer helpful, joint replacement of the hips and knees may be considered. bone deformity — cutting and realignment of pagetic bone (osteotomy) may help painful weight bearing joints, especially the knees. complications resulting from enlargement of the skull or spine may injure the nervous system. however, most neurologic symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery. diet and exercise in general, patients with paget's disease should receive 1000–1500 mg of calcium, adequate sunshine, and at least 400 units of vitamin d daily. this is especially important in patients being treated with bisphosphonates; however, taking oral bisphosphonates should be separated from taking calcium by at least two hours, because the calcium can inhibit the absorption of the bisphosphonate. patients with a history of kidney stones should discuss calcium and vitamin d intake with their physicians. exercise is very important in maintaining skeletal health, avoiding weight gain, and maintaining joint mobility. since undue stress on affected bones should be avoided, people with paget's disease of bone should discuss any exercise program with their physicians or physical therapists before beginning. prognosis the disease is progressive and slowly worsens with time, although people may remain minimally symptomatic. treatment is aimed at controlling symptoms, but there is no cure. any bone or bones can be affected, but paget's 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 paget's 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 paget's disease of bone is the second most common metabolic bone disorder, after osteoporosis. the overall prevalence and severity of paget's disease are decreasing; the cause for these changes is unclear. paget's 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 paget's disease in about 3 percent of people older than 40 years of age. paget's disease is more common in males than females. rates of paget's disease are about 50 percent higher in men than in women. about 15 percent of people with paget's 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 paget's disease varies considerably with geographic location. paget's predominantly affects people of european descent, whereas people of african, asian, or indian descent are less commonly affected. paget's disease is less common in switzerland and scandinavia than in the rest of western europe. paget's disease is uncommon in the native populations of north and south america, africa, asia, and the middle east. when an individual from these regions does develop paget's disease, there is typically some european ancestry present. history the condition was initially described by dr. james paget. in a paper published in 1877, paget told of five patients with "a rare disease of bones" which presented with slowly progressive bone deformities in the 4th and 5th decades of age. strikingly, the first patient was described to have many of the classic complications of the disease, including arthritis related to abnormal bone mechanics, cranial nerve palsies associated with an enlarging skull, and malignant transformation of a tumor of the radius which ultimately proved fatal. paget's post-mortem autopsy evaluation showed "bones of the vault of this skull were in every part increased to about four times the normal thickness," and microscopic evaluation showed evidence of both bone erosion and abnormal remodeling. although he incorrectly attributed the findings to a process of chronic inflammation, having ruled out tumor and hypertrophy as alternative etiologies, these prescient observations of a mixed destructive/regenerative process correspond to the modern understanding of the disease. holding, then, the disease to be an inflammation of bones, i would suggest that, for brief reference, and for the present, it may be called, after its most striking character, osteitis deformans. a better name may be given when more is known of it.— james paget, paget j. on a form of chronic inflammation of bone (osteitis deformans). medico-cirurgical transactions of london 1887;60:37-63. paget's disease of bone was originally termed osteitis deformans, because it was thought to involve an inflammatory process, which is implied by the suffix -itis. now, that term is considered technically incorrect, and the preferred term is osteodystrophia deformans. society and culture ludwig van beethoven is speculated to have had paget's disease based on autopsy description, and which may have contributed to his well-known deafness. retired boston red sox center fielder dom dimaggio had paget's disease and served as a member of the board of directors of the paget foundation.