Extensive Paget's Disease Research Articles

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level—1971 IU/L [normal 31–110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7–10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12–72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8–38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.

Paget???s Sarcoma

Paget's sarcoma is a rare entity that principally occurs in elderly people with extensive Paget's disease. The primary sites of occurrence are the pelvis, proximal femur, proximal humerus, and calvarium. The lesions are highly malignant and the patients frequently are found to have metastases at the time of discovery. The survival rate reported in the literature generally is very poor. We were able to locate 16 patients with Paget's sarcoma in the Dr. Henry L. Jaffe Pathology Collection treated from 1942 to 1967. These were added to 27 patients treated for the disease by the Harvard Orthopaedic Oncology Group from 1972 to 2001. Three were giant cell tumors, which are occasionally found in patients with florid Paget's disease but are not malignant. Of the remaining 40 patients, outcome data were available on 35 patients. The rate of Musculoskeletal Tumor Society Stage III tumors was very high (35%) and the rate of survival was 14% at approximately 2.5 years, without differences between the two series. In view of the remarkable concordance in the poor survival figures for patients treated between 1946 and 1967 and those treated between 1972 and 2001 it appears that little progress has occurred in the treatment of Paget's sarcoma over the years, which is in sharp contrast with the current statistics for standard osteosarcoma. Prognostic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

The Articular Manifestations of Paget??s Disease of Bone

Disorders of joints are commonly associated with Paget's disease of bone but are often disregarded or attributed to the underlying Pagetic condition. The authors evaluated a 69-year-old man with extensive Paget's disease of bone, degenerative arthritis, calcific periarthritis, and gout. The degenerative arthritis and calcific periarthritis of the shoulders was originally mistaken for Paget's disease of the proximal humerus. The wrist arthritis was attributed to Paget's disease until evaluation of surgical pathology specimens showed intraarticular gouty granulomas. In evaluating and treating a patient with Paget's disease of bone, the orthopedic surgeon should be aware that the successful treatment of associated articular disorders may require therapeutic measures in addition to those used in treating the Paget's disease.

Benign giant cell tumor complicating extensive Paget's disease

Benign giant cell tumor complicating extensive Paget's disease

Paget's Disease of Bone

Publisher Summary This chapter discusses Paget's disease with special attention particularly on the experience gained in the Endocrine Unit of the Royal Postgraduate Medical School over the past 20 years. The overall incidence of Paget's disease in the United Kingdom, based on radiological surveys, is 5%. Comparisons have been made between the findings in Pagetic osteoclasts and those of nerve cells in subacute sclerosing panencephalitis, which represents a slow virus infection. Pagetic pain must be distinguished from arthritic pain, which is not uncommon in affected patients either coincidentally or in connection with the disease. Extensive Paget's disease may cause an increase in cardiac output, although true high-output failure is most rare. Bone formation and resorption are normally linked or coupled together, and this is the overall situation in Paget's disease. The interpretation of biochemical parameters in relation to focal disease activity in Paget's is not straightforward.

Osteomyelitis of the mandible as a complicating factor in paget's disease of bone

A case of osteomyelitis of the mandible in a patient with extensive Paget's disease of bone is presented. The changes in the bone with Paget's disease makes the diagnosis, clinical assessment and management of the osteomyelitis in such patients a difficult task.

Determination of hydroxyproline polypeptides in urine and blood serum by gel filtration

Hydroxyproline-containing polypeptides were isolated from urine by filtration on polyacrylamide gel Bio-Gel P-2. This fraction was quantitatively and qualitatively similar to the nondialysable hydroxyproline in urines of normal adult subjects, patients with chronic uremia, and with primary or secondary hyperparathyroidism. Hydroxyproline polypeptides isolated from urines of patients with extensive Paget's disease or from normal growing subjects contained a group of smaller polypeptides slightly retarded on Bio-Gel P-2 which were not retained by the dialysis membrane Spectrapor™. In these two groups of subjects the values of hydroxyproline polypeptides were 35–45 percent higher than those of dialysable hydroxyproline. Increased excretion of hydroxyproline polypeptides was found in chronic uremia, primary and secondary hyperparathyroidism, Paget's bone disease and in normal growing subjects. With the notable exception of chronic uremia the excretion of hydroxyproline polypeptides paralleled that of total and oligopeptidic hydroxyproline. In some cases of chronic uremia the polypeptidic hydroxyproline represented the predominant fraction. On long columns of Bio-Gel P-6 hydroxyproline polypeptides separated into several peaks. The chromatographic pattern was rather characteristic for chronic uremia, secondary hyperparathyroidism, Paget's bone disease and physiological growth. A hydroxyproline fraction of similar Chromatographic properties was isolated from blood serum after deproteinisation with heat or ethanol at pH 4.8. High serum levels of this hydroxyproline fraction were observed in pathological conditions with increased urinary excretion of polypeptidic and nondialysable hydroxyproline.

The cardiac output in paget's disease before and after treatment with cortisone

1. 1. Observations on the cardiac output have been made in six patients with extensive Paget's disease before and during treatment with large doses of cortisone. 2. 2. In all cases, cardiac output was elevated before treatment. High doses of cortisone for a sufficient duration, more than three days and less than nine days, produced a pronounced fall to normal levels. Serum alkaline phosphatase levels changed in the same direction as the cardiac output. 3. 3. Cortisone had no consistent effect on oxygen consumption, large vessel hematocrit, total blood volume, pulse pressure or mean arterial pressure. Cortisone therapy resulted in a pronounced drop in pulse rate in three of the six patients studied. 4. 4. The mechanism through which cortisone exerts its effect on cardiac output in Paget's disease was not elucidated by these studies.