Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study.

Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. INTRODUCTION: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. MATERIALS AND METHODS: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. RESULTS AND CONCLUSIONS: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.     

Circulating 1,25-Dihydroxycholecalciferol After Intravenous Injections of l{alpha}-Hydroxycholecalciferol in Patients on Regular Haemodialysis

The formation of 1.25-dihydroxycholecalciferol (1.25-(OH)₂D₃after single intravenous injections of 1-hydroxycholecalciferol(1-OHD₃) was examined in four patients with chronic renal failureon regular haemodialysis. Following 1–3µg 1-OHD₃administered at weekly intervals, 1.25-(OH)₂D₃ appeared in thecirculation within 1 h, and peak concentrations were reachedbetween 2 h and 5 h. By 8 h serum 1.25-(OH)₂D₃ concentrationshad started declining and by 44 h they had returned to baselineafter 1µg 1-OHD₃ but they were still above basal after2 and 3 µg by an average of 30 pmol/l. One week afterinjections, concentrations were back to basal in all patientsstudied. The serum 1,25-(OH)₂D₃ dose response to injected la-OHDwas linear, indicating ample capacity of the liver 25-hydroxylaseto further hydroxylate 1-OHD. However, examination of the individualresponses revealed lower increments in serum 1.25-(OH)₃ concentrationsin the patients with the highest basal serum 25-hydroxyvitaminD concen trations. Intravenous 1-OHD₃ may be useful in the furtherstudy of the interactions between 1.25-(OH)₂₃ calcium and PTHin chronic renal failure, as well as of the hepatic metabolismof vitamin D.     

SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development.

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or beta-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression.     

The relationship between phalangeal bone density and vertebral deformities

Radiographic absorptiometry (RA) of the phalanges is a convenient and reliable technique for measuring bone mineral density (BMD). It needs only a radiograph of the hand, which can be sent for evaluation to a central facility, whereas other techniques require specialized equipment. We assessed the relationship between RA measurements and the presence of vertebral deformities in a population-based cohort of postmenopausal women, and to compare the results with simultaneously obtained BMD of the hip by dual-energy X-ray absorptiometry (DXA). A total of 389 women aged 55–84 (mean age 67.2 years, SD 8.7) were randomly selected from a large general practice. RA, DXA of the hip, and vertebral deformities in the lateral spine X-rays by vertebral morphometry were assessed. Thirty-eight women (9.8%) had severe (grade II) vertebral deformities, and their BMD at the phalanges and femoral neck was significantly lower than that of women without severe vertebral deformities. Odds ratios for the presence of severe vertebral deformities of 1.5 (95% CI: 1.1–2.1) for RA and 1.3 (95% CI: 0.9–1.9) for DXA, together with similar receiver operating characteristics curves, were found using age-adjusted logistic regression. Phalangeal BMD is related to vertebral deformities at least as closely as BMD of the femoral neck BMD. RA may therefore help to evaluate fracture risk, especially if no DXA equipment is available. Received: 21 July 1998 / Accepted: 1 July 1999     

Who will benefit from antiresorptive treatment (bisphosphonates)?

Bisphosphonates are very effective treatments of postmenopausal osteoporosis. They suppress bone turnover, increase bone mineral density (BMD), and maintain or improve structural and material properties of bone, thereby decreasing the risk of fractures. All patients selected for treatment according to current international guidelines can benefit from bisphosphonate therapy independently of their prevalent rate of bone turnover. Long-term extensions (up to 10 years) of pivotal clinical trials with daily bisphosphonate administration showed sustained efficacy with no evidence of adverse effects on bone metabolism and skeletal fragility. Recent studies focus on the resolution of the effects of bisphosphonates on bone metabolism and fracture risk following cessation of long-term treatment. Such studies may help to formulate treatment recommendations according to the risk of the individual patient.     

Three-dimensional analysis of the left anterior descending coronary artery: comparison with conventional coronary angiograms

OBJECTIVE: This study aimed at comparing three-dimensional (3-D) reconstruction with two-dimensional coronary angiograms with respect to anatomical parameters that might affect plaque formation and rupture. METHODS: Sixty patients with stable left anterior descending (LAD) lesions and 60 patients with an anteroseptal myocardial infarction and recanalized LAD were studied. RESULTS: Conventional angiography significantly underestimated the distance of the stenosis from the ostium of the LAD, 29.4+/-14.5 versus 35.3+/-18.5 mm, P<0.001. Vessel curvature at the site of the lesion was overestimated by conventional angiography compared with 3-D reconstruction, 147.6+/-30.6 degrees versus 162.3+/-11.2 degrees , P<0.001, as was axial bending of the LAD owing to ventricular contraction (17.8+/-7.78 degrees vs. 8.9+/-8.9 degrees , P<0.001). No agreement was observed between two-dimensional and 3-D analysis for either curvature on lesion or axial bending assessment, with intraclass correlation coefficient values 0.155 (-0.009, 0.315) and -0.022 (-0.183, 0.174), respectively. No significant agreement was found between the two methods in the detection of on-stenosis bifurcations (1.7%, kappa=0.086, P=0.349). CONCLUSION: Conventional coronary angiography cannot provide accurate estimates of anatomical parameters, such as distance of a coronary stenosis from the ostium of the vessel, coronary artery curvature at the site of stenosis, axial deformity and bending because of ventricular contraction, and classification of bifurcations. Reconstruction of the coronary tree in 3-D space is necessary for such estimations.     

Plasmodium vivax Pre-Erythrocytic-Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

Abstract. The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy- individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic-stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy- donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria.