Paget's disease and sensori-neural deafness: temporal bone histopathology of Paget's disease

Four cases with Paget's disease of the temporal bone are presented to illustrate the pathogenesis of the associated deafness. One case illustrates the combination of severe deafness due to bilateral otosclerosis with probably asymptomatic bilateral Paget's disease. One case with advanced Paget's disease presents features to explain early stages of sensori-neural deafness before actual cellular invasion of the inner ear. One case of profound deafness due to Paget's disease presents a different stage of cellular invasion of the inner ear by the disease on each side. One case illustrates invasion of the internal auditory meatus by Paget's disease with infiltration of the acoustic division of the nerve and profound deafness.     

Quantitative bone scintigraphy in the management of monostotic Paget's disease of bone

OBJECTIVE: To assess the use of quantitative bone scanning (QBS) in the monitoring of patients with intravenous pamidronate-treated symptomatic monostotic Paget's disease of bone in whom biochemical markers of bone turnover are relatively normal. METHODS: QBS was performed in 9 patients and the results were expressed as a ratio, obtained by comparing isotope uptake at an affected and a control (unaffected) site. RESULTS: Serum alkaline phosphatase levels were normal in 7 of the 9 patients and changed minimally with treatment. The median QBS ratio was 2.72 (range 1.69-24.6) at baseline and 1.49 (range 0.63-4.18) posttreatment (P = 0.008). The median symptom score decreased with treatment, but QBS ratios provided the only objective measure of disease activity by which response to pamidronate therapy could be judged. CONCLUSION: QBS may be a useful technique for evaluating the effects of treatment in patients with Paget's disease of bone.     

Paget's disease of bone complicated by giant cell tumor

Paget's disease is uncommon in patients younger than 50 years of age. Multifocal giant cell tumors arising in bone affected by Paget's disease have been described previously in 37 cases. A case of a 38-year-old man with polyostotic Paget's disease and multifocal giant cell tumors responsive to steroid therapy is presented.     

Significance of renal visualization during bone scanning in Paget's disease

In 17 of 26 patients with extensive, symptomatic Paget's disease poor renal visualization was noted on bone scanning with 99mTc-diphosphonate. Renal function was normal in all patients. The intensity of the renal image proved to be inversely related to the extent and metabolic activity of the Pagetic process. This finding supports the hypothesis that in Paget's disease the balance between skeletal and renal extraction of circulating tracer amy be displaced in favor of the former.     

Intermittent treatment of Paget's disease of bone with calcitonin: histological study

The authors report the results of a semi-quantitative histological study of bone carried out in 6 patients with Paget's disease treated with salmon calcitonin (about thirty injections of an average of 50 MRC units) over 8 to 14 weeks. The treatment led to a decrease in the resorption surfaces, in the number and the nucleation of the osteoclasts, and in the level of hydroxyprolinuria. Cessation of treatment led to an increase in these parameters, but starting from the fifth month after the cessation renewed improvement was noted, concerning in particular the hydroxyprolinuria and the nucleation of the osteoclasts and this lasted until the tenth month. The possibility of a prolonged action of calcitonin indicates that discontinuous therapy of Paget's disease should be considered (4 months per year, for example).     

Pamidronate is effective for Paget's disease of bone refractory to conventional therapy

Paget's disease of bone is characterized by primary osteoclastic dysfunction and prolonged treatment with conventional medications including calcitonin and etidronate, results in a number of patients becoming refractory to treatment. We have evaluated the effectiveness of three dosage regimes of aminohydroxypropylidene bisphosphonate (pamidronate) in 15 patients with extensive Paget's disease who had become refractory to conventional therapy. Nine patients had pamidronate (intravenous infusion of 30 mg over 4-5 hours at monthly intervals) for 6 months. A further four patients received 30 mg of pamidronate infusion daily for 6 consecutive days and another two patients, 60 mg on 3 consecutive days (total dose of 180 mg/patient). In all three groups the bone-specific alkaline phosphatase and urinary hydroxyproline excretion both fell by 75% (P < 0.001). All but one patient showed a marked improvement in clinical symptomatology (pain and mobility) and biochemical parameters indicating decreased bone turnover. Remissions achieved (> 12 months) with all three regimens were comparable. The pagetic bone pain was reduced and the mobility was significantly improved after 3 months of therapy and was continued for up to 1 year. Currently, it may be difficult to justify the use of intravenous bisphosphonate as the first line of therapy for Paget's disease, but it does seem to have a definite place in patients with severe Paget's disease who do not respond to other therapeutic agents. Here we demonstrate that pamidronate is highly effective in patients with extensive Paget's disease who became refractory to conventional treatment. Further studies are necessary to optimize the dosage and frequency of administration of pamidronate.     

Diphosphonate treatment of Paget's disease

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.     

Risedronate in the treatment of Paget's disease of bone: an open label, multicenter study

An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by > or = 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile.     

Ulnar nerve palsy in Paget's disease

A 73-year-old housewife with enlargement of her distal right humerus and especially the medial epicondyle due to Paget's disease developed an ulnar nerve palsy. Transposition of her ulnar nerve anterior to her elbow completely relieved her symptoms. A similar case of ulnar nerve palsy associated with expansion of the distal humerus due to Paget's disease seems not to have been previously reported.     

Anesthetic management of a Paget's disease patient complicated with Parkinson disease

Paget's disease is a metabolic disorder of unknown etiology characterized by excessively rapid remolding of bone. We report a case of Paget's disease complicated with Parkinson syndrome. A 69-year-old female patient was scheduled for ventriculo-peritoneostomy due to hydrocephalus. Her manifestations included disability to walk, slight deafness and muscular rigidity of limbs, without symptom of intracranial hypertension. After induction of anesthesia with thiopental and vecuronium, tracheal intubation with Macintosh laryngoscope was attempted but failed because mouth opening was restricted to only 3 cm. Again with Bullard laryngoscope, she was successfully intubated. During neurosurgical operation, the anesthesia was maintained with low concentration of isoflurane (under 0.3%), nitrous oxide and oxygen. The surgery was completed without adverse events such as disorder of autonomic nervous system. However 6-days after operation, ventilatory arrest occurred due to bronchial obstruction with sputum. Immediately, re-intubation was performed without any sequela and tracheostomy was also performed. In conclusion, as reported previously, intubation and postoperative pulmonary dysfunction should be carefully taken care of, and Bullard laryngoscope was useful for this patient.