Vitamin D Status in Males in Jerusalem Area and Its Correlation to Parathyroid Hormone (PTH) Level and Bone Mineral Density
Condition: Vitamin D Deficiency; Secondary Hyperparathyroidism; Osteomalacia
MeSH terms: Osteomalacia; Vitamin D Deficiency; Hyperparathyroidism; Hyperparathyroidism, Secondary
Study type: Interventional
Phase: Phase 4

Summary: 
      Because of its high sun exposure, Israel was traditionally supposed to be protected from
      vitamin D deficiency, and the country food products hardly contain vitamin D supplements.
      However the Jerusalem ultra-Orthodox population, which constitutes a significant fraction of
      the city population, is at risk of developing vitamin D deficiency due to low sun exposure,
      as consequence of its dressing code covering most of the body and very limited time of
      outside activities. The investigators aim is to check whether vitamin D deficiency is found
      more frequently in the ultra-Orthodox male population in comparison to a non-ultra-Orthodox
      male population, and to study its eventual consequences. Correlation between vitamin D levels
      and PTH levels will be examined, according to age and to creatinine levels. Bone mineral
      density (BMD) will be evaluated in 2 selected subgroups of subjects (with lowest and highest
      vitamin D levels), and re-evaluated after 6 months of vitamin D supplementation in vitamin
      D-deficient subjects. An increase in BMD within 6 months would suggest osteomalacia as the
      main cause of low BMD in these subjects.
    

Detailed description: 
      Subjects:

      The study will include 200 males aged 18-70, living in the Jerusalem area. Enrollment will be
      distributed among 8 clinics of the Clalit Health Services: 4 clinics located in predominantly
      ultra-Orthodox areas (group A) and 4 clinics located in mixed areas (Group B).

      Each group of clinics will enroll 100 subjects as sub-defined:

      Age 18-24: 30 patients (Groups A1 and B1) Age 25-39: 30 patients (Groups A2 and B2) Age
      40-54: 20 patients (Groups A3 and B3) Age 55-70: 20 patients (Groups A4 and B4)

      Study protocol:

      Enrollment will be performed by the physicians participating in the study and the nurses
      working in the corresponding clinics, after advertisement of the study in the clinics.

      Visit 1:

        1. The subjects will receive information about the study aims and protocol and will sign an
           informed consent form.

        2. Blood pressure, height and weight will be measured and BMI calculated.

        3. The subjects will fill a questionnaire concerning their personal habits: dressing code,
           degree of sun exposure, physical activity, smoking, alcohol consumption, muscular pains
           and general fatigue.

        4. The physician (co-investigator) signing the informed consent form will rule out subjects
           presenting pre-defined exclusion criteria.

        5. Blood samples will be drawn for: calcium, phosphorus, PTH, 25 OH Vitamin D, 1,25 OH
           Vitamin D, magnesium, creatinine, alkaline phosphatase, albumin.

        6. A urine sample will be collected for magnesium and calcium/creatinine ratio.

      The subjects will receive the lab results by mail, with a recommendation to consult their
      family physician in order to receive treatment in case of vitamin D deficiency. (Vitamin D
      levels <20 ng/ml)

      The subjects in the 18-39 age groups (Groups A1, A2, B1 and B2) will be classified according
      to their vitamin D levels. The 20 subjects presenting the highest vitamin D levels or with
      vitamin D level>30 ng/ml will constitute the "high D" group and the 40 subjects with the
      lowest vitamin D levels will constitute the "low D" group. (We expect the vitamin D levels to
      be above 30 ng/ml in the "high D" group and below 10 ng/ml in the "low D" groups, according
      to the results of our pilot study).

      Subjects with vitamin D level>30 ng/ml or <10 ng/ml can be enrolled to the 60 patients of the
      "high D" and "low D " groups and will proceed to visits 2 and 3.

      Visit 2:

      60 subjects (20 from the "high D" group and 40 from the "low D" group) will undergo a bone
      mineral density examination in the Osteoporosis Center of Mount-Scopus Hadassah Hospital. All
      subjects with low vitamin D levels will receive a 6-month vitamin D supplementation of 2000
      units per day for the first 12 weeks and of 1000 units per day for the next 12 weeks.

      Visit 3:

      The 60 subjects who underwent visit 2 will undergo visit 3 six months later.

        1. The subjects will fill a questionnaire similar to the first one and detail their degree
           of compliance with vitamin D supplementation

        2. Blood samples will be drawn for plasma levels of: calcium, phosphorus, magnesium, PTH,
           25 OH vitamin D, 1,25 (OH)2 vitamin D, creatinine, alkaline phosphatase, albumin

        3. A urine sample will be collected for magnesium and calcium/creatinine ratio.

        4. A repeat bone mineral density examination will be performed in the Osteoporosis Center
           Mount-Scopus Hadassah Hospital

      The subjects will receive their test results by mail with a recommendation to consult their
      family physician in case of persistent abnormal results.
    

Intervention name(s): 25 OH vitamin D
Intervention type(s): Drug
Intervention description(s): oral supplementation of 25 OH vitamin D at dose of 2000 units/d for 3 months then 1000 units/d for 3 months
Intervention MeSH terms: Vitamin D
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening