Is clinical expressiveness of Paget's disease of bone decreasing?

Recent data have suggested secular changes implying a current trend toward decreased clinical severity of Paget's disease of bone (PD). To test this hypothesis, we conducted a study comparing the characteristics of two groups of PD patients, as disclosed from a sample assessed systematically. The investigation was a hospital-based study of all cases followed up at our unit since 1980. Throughout the follow-up period, diagnosis was based on standard X-ray criteria and the same clinical assessment was applied. Group I (n = 124) represented patients born before 1926, whereas group II (n = 109) included those born after that year. A bone scan performed with 99mTc-EHDP was available for all patients. X-rays of the pelvis and spine, and views of any hot spot observed on the scintigraphy scans were reviewed. The skeletal extent of PD, based on bone scan uptake, was determined by using the index proposed by Coutris. Alkaline phosphatase and hydroxyproline excretion levels were determined in blood and urine, respectively. Baseline characteristics were recorded on a purpose-designed computerized database. The proportion of males (47% in group I vs. 65% in group II; p = 0.007) and the mean (+/-SD) age at diagnosis (69.0 +/- 8.15 vs. 54.3 +/-9.14; p < 0.001) differed significantly between groups. The year of birth showed a strong negative correlation with age at diagnosis (r = -0.83, p < 0.0001) and a weak, but significant, negative correlation with extent of bone lesion (r = -0.20; p = 0.002). Likewise, subjects born prior to 1926 showed a greater percentage of affected skeleton cases (9.6 plus minus 8.01 vs. 7.06 +/- 5.79; p = 0.001). Group I individuals who had pelvic and/or femoral bone lesions were more prone to suffer "pagetic coxopathy" (65% vs. 40%; p = 0.003) with "protrusio acetabuli" (32% vs. 17%; p = 0.01), and the percentage of patients showing radiographic Monckeberg-type vascular calcifications (36% vs. 14%; p = 0.0006) was higher than in those born after 1926. No other epidemiologically clinically, or biochemically relevant differences were seen in the crude analysis. Multivariate analysis identified extent of skeletal lesions (OR = 0.76; p = 0.01), age at diagnosis (OR = 0.79; p = 0.008), number of bones involved (OR = 1.53; p = 0.03), and occupation (p < 0.0001) as the predictive variables linked to year of birth. Our data are consistent with a temporal tendency toward a smaller number of bone lesions and a decreased percentage of instances of affected skeleton. An earlier age at recent diagnosis times and absence of any relevant clinical or biochemical differences seems more likely linked to recent changes in referral and sociological patterns.

Assessment of cardiac function by echocardiography in Paget's disease of bone.

OBJECTIVE: To identify the mechanisms which influence the development of cardiac insufficiency in Paget's disease of bone (PD). METHODS: In this hospital-based case-control study 23 consecutive, recently diagnosed and untreated PD patients were compared against 23 controls frequency-matched by sex, age and body index. All subjects underwent non-invasive assessment of cardiac function by two-dimensional Doppler echocardiography. Calcium, phosphate, and creatinine were determined in the serum and urine, along with alkaline phosphatase and hydroxyproline excretion, two biochemical parameters of PD activity. RESULTS: Peripheral vascular resistance proved lower (1604.9 +/- 390.1 vs 1801.2 +/- 421.0) and the stroke volume higher in PD patients (67.2 +/- 14.4 vs 56.0 +/- 8.6; p = 0.07) compared with controls. These differences were greater (1504.7 +/- 289.9 and 71.0 +/- 6.2) and attained statistical significance (p = 0.008) when the subgroup with more extensive skeletal disease only was considered. A moderate correlation was observed between hydroxyproline excretion and the E/A ratio (r = 0.45; p = 0.03), peripheral vascular resistance (r = -0.42; p = 0.04), and diastolic arterial pressure (r = -0.42; p = 0.04). The final model obtained via multivariate analysis identified both urinary hydroxyproline and age as predictive variables linked to peripheral vascular resistance. CONCLUSION: In the early phases of PD there is a trend towards a reduction in peripheral vascular resistance. If this persists, it may lead progressively to increased cardiac output, which is mainly influenced by the degree of turnover impairment and the age of the individual.

Frequency and characteristics of familial aggregation of Paget's disease of bone.

The cause of Paget's disease of bone (PDB) is unknown. In an attempt to ascertain the proportion of familial cases and evaluate the influence of genetic factors on the occurrence of the disease, a study was undertaken based on 35 PDB patients from our Unit. Their families were investigated, with the participation of a total of 128 first-degree relatives. Fourteen (40%) of these 35 index cases had at least one other first-degree relative affected with PDB and were defined as "familial." The remaining 21 (60%) were considered "sporadic." The frequency of males in the familial cases (79%) was significantly higher than among the sporadics (29%; p < or = 0.01). Mean age at diagnosis (63.1 +/- 12.6 vs. 71.3 +/- 8.7; p < or = 0.02), proportion of polyostotic cases (85.7% vs. 52.4%, p < or = 0.05), and mean number of involved bones per patient (4.36 +/- 2.50 vs. 2.33 +/- 1.93, p < or = 0.01) differ significantly in the familial and sporadic groups. The disease appears to be transmitted via both paternal and maternal sides, and pedigree analysis suggested an autosomal dominant inheritance or multifactorial mechanism. Apart from green-and-blue eye color, which was clearly associated with familial grouping (OR 6.25, 95% CI 1.15-37.16, p < or = 0.01), crude analysis on several genetically based traits and environmental variables revealed no other significant differences between the groups. The adjusted odds ratio estimated for green-and-blue eye color was 2.92 (95% CI 0.38-22.74).(ABSTRACT TRUNCATED AT 250 WORDS)