Conducted by the agencys 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 Pagets disease for which surgery may be recommended.
Differential diagnosis
Treatment
Although initially diagnosed by a primary care physician, endocrinologists (internal medicine physicians who specialize in hormonal and metabolic disorders), rheumatologists (internal medicine physicians who specialize in joint and muscle disorders), orthopedic surgeons, neurosurgeons, neurologists, oral and maxillofacial surgeons, and otolaryngologists are generally knowledgeable about treating Pagets disease and may be called upon to evaluate specialized symptoms. It can sometimes be difficult to predict whether a person with Pagets disease, who otherwise has no signs or symptoms of the disorder, will develop symptoms or complications (such as a bone fracture) in the future. Medication
The goal of treatment is to relieve bone pain and prevent the progression of the disease. These medications are usually recommended for people with Pagets disease who:
have bone pain, headache, back pain, or a nerve-related symptom (such as "shooting" pains in the leg) that is directly associated with the disease;
have elevated levels of serum alkaline phosphatase (ALP) in their blood;
display evidence that a bone fracture will occur;
require pretreatment therapy for affected bones that require surgery;
have active symptoms in the skull, long bones, or vertebrae (spine);
have the disease in bones located next to major joints, placing them at risk of developing osteoarthritis;
develop hypercalcemia that occurs when a person, with several bones affected by Pagets disease and a high serum alkaline phosphatase level, is immobilized. Bisphosphonates
Five bisphosphonates are currently available. In general, the most commonly prescribed are risedronic acid, alendronic acid, and pamidronic acid. Etidronic acid and other bisphosphonates may be appropriate therapies for selected patients but are less commonly used.