ENDOCRINE NEWS

Vitamin D & Bone Health

By Cathy Kristiansen, Endocrine News November 2006

Dr. Bikle, Professor in Residence, Medicine, at the University of California, San Francisco, has a wealth of experience in the basic and clinical aspects of vitamin D metabolism and function. His session was titled, "Screening for & Treating Vitamin D Deficiency." In 50 minutes, his talk could not be a comprehensive analysis of vitamin D insufficiency and deficiency, so he focused his comments on audience questions. Here are some highlights:

Target Range


There is no single target level of serum 25-hydroxyvitamin D [25(OH)D] acceptable to all physicians, but Dr. Bikle defends the target of 80 nmol/L or the equivalent of 32 ng/mL. "I believe about 30 ng/mL is a decent number, and-this is controversial and I'll have vitamin D zealots on my head for what I'm about to say-probably the juice is not worth the squeeze to get much above!" He noted that in Scandinavia and the Netherlands, a target of 20 ng/mL might be regarded as acceptable, given that the typical diet is calcium rich with cheese and bony fish, but a higher target is appropriate in the United States.

Best for Bones


  • On the benefit to bone mineral density of raising serum 25(OH)D levels in different ethnic populations, Dr. Bikle cited a study showing that African Americans and Hispanics gained density until their 25(OH)D reached about 30 ng/mL, although Caucasians continued to gain density as far as the study went.
  • A study on intestinal calcium absorption in females also showed a steady increase until 25(OH)D edged above about 30 ng/mL.
  • A study measuring falls and fractures found that individuals treated with 700-800 units (IU) of vitamin D had significantly lower rates of falling and fractures, but other studies using only 400 IU or recording poor compliance were less successful at preventing falls and fractures, Dr. Bikle said.
  • Also suggesting a 30 ng/mL 25(OH)D level was a study on proximal muscle weakness, which relates to a patient's stability and predisposition to fall if the muscles are weak. One test measured how long a patient took to sit down in a chair and stand up 3 times and another how long it took to walk 400 meters. "Obviously, the longer it takes you to do these tests, the worse your muscle strength," Dr. Bikle said.

Measuring Vitamin D


It is helpful to measure both 25(OH)D2 and 25(OH)D3 to monitor the full effect of vitamin D2 supplementation on total vitamin D levels. One widely used assay is the DiaSorin radioimmunoassay, but lab results have tended to vary greatly. However, labs are standardizing more now, Dr. Bikle said. An excellent test used in the past was the quantitative high performance liquid chromatography (HPLC) method, but it is too labor intensive to be used much today. New tests in development are based on mass spectrometry.

Whom to Screen


Vitamin D3 comes from diet or is formed in the skin after ultraviolet irradiation. It is further hydroxylated in the liver to 25(OH)D3 as the first step of its conversion. Dr. Bikle noted that as a person ages, the skin becomes less effective in this function, so an older person needs more sunlight exposure. There are no data to suggest that 25(OH)D absorption or conversion in the liver declines with age. However, the kidney is less effective at making dihydroxyvitamin D [1,25(OH)2D]) for any given parathyroid hormone (PTH) level, so PTH production rises to compensate. Additionally, the PTH level negatively correlates with 25(OH)D levels at least until 25(OH)D rises above 30 ng/mL, suggesting that 25(OH)D itself or its conversion to 1,25(OH)2D in the parathyroid gland might be a controlling factor. In an ideal world, all patients of any age would be tested for vitamin D during routine medical visits. But physicians typically measure those who are most at risk, including:

  • Patients more than 60 years old, particularly women, because skin as it ages becomes less effective at making vitamin D, so an older person needs more sunlight. "If you are dealing with this young college athlete who is out there on her bicycle, going up and down mountains, 8 hours a day, chances are that she is getting enough sunlight," he mused.
  • People with more pigment in their skin, such as some African Americans: "The more pigment in the skin, the less vitamin D is going to be made for any given level of sunlight," he noted.
  • Heavy users of sunscreen: "If your patients say they avoid the sun with a passion, everyone knows that the sun is a killer, that you're going to break out with cancer all over your skin just walking to the drug store, you'll want to screen them."
  • People who have any history of malabsorption or who have had GI operations.
  • Anyone who has lactase deficiency who says "I haven't touched milk for 20 years, can't stand the stuff, it makes me sick."
  • Patients under treatment for osteoporosis. Dr. Bikle added that season is an important factor to bear in mind when screening, because vitamin D levels are typically lower in months with less light or sunshine.

Treatment


The main treatment is vitamin D, provided the patient does not have hypercalciuria that would be revealed in urine calcium testing. To urgently raise a patient's 25(OH)D level from near 15 ng/mL to 30 ng/mL, Dr. Bikle said he uses 50,000 IU of D2 weekly and continues for a month before checking the urine calcium to determine the next step. For someone deficient-at 10 ng/mL or less-he would continue that dose for at least 6 to 8 weeks. Although not readily available in high doses, D3 should be given in preference to D2 because it is more biologically active, in part because it is less rapidly cleared. But either form of vitamin D will work. When asked about the benefit of giving mega doses every 3 months, he recommended against it, although the data are scant for this means of administration. Because of its quicker clearance, if D2 is given only every 3 months, during much of that time the vitamin D levels may not be in the desired range. He added that taking a dose of 800 IU daily is not toxic, given that it translates into 25(OH)D increments of only 8 ng/mL, and substantially higher doses (e.g., 2,000 IU daily) are probably safe for most individuals.

During wintertime, with less sunlight, routine vitamin D supplementation should be greater than in summer. "Unless you are very fair and very sensitive to sunlight, a moderate amount of exposure to sun is the best way to get your vitamin D during the time you can make it, but you can't make it all year long," he said. "Skin is the best source of vitamin D in my humble opinion," he elaborated. "I can't prove to you that the vitamin D made in the skin is any better than the vitamin D you can buy at the drugstore—hopefully, one day I will."