Paget's Disease of Bone in The Netherlands: A Population-Based Radiological and Biochemical Survey—The Rotterdam Study

Authors

  • Marelise EMW Eekhoff,

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
    2. Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands
    3. Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
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  • Marjolein van der Klift,

    1. Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands
    2. Department of Epidemiology, Erasmus University, Rotterdam, The Netherlands
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  • Herman M Kroon,

    1. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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  • Cyrus Cooper,

    1. MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom
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  • Albert Hofman,

    1. Department of Epidemiology, Erasmus University, Rotterdam, The Netherlands
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  • Huibert AP Pols,

    1. Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands
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  • Socrates E Papapoulos

    Corresponding author
    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
    • Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
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  • The authors have no conflict of interest.

Abstract

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.

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