Superiority of alfacalcidol over plain vitamin D for glucocorticoid-induced osteoporosis
Alfacalcidol for glucocorticoid-induced osteoporosis. This interesting German study by Ringe JD and others compared 1,000 IU plain (vitamin D3) vitamin D or 1 microg alfacalcidol, each used with 500 mg calcium daily, to treat glucocorticoid-induced osteoporosis (GIOP). All patients had been on long-term glucocorticoid (GC) therapy. Lumbar spine BMD at baseline for each group was -3.26 and -3.25 for the alfacalcidol and vitamin D3 groups, respectively. At the femoral neck it was -2.81 and -2.84 respectively via T-score. After the 3-year study there was a highly statistically significant increase in BMD at the lumbar spine and femoral neck of the alfacalcidol group compared to the vitamin D3 group. There was also a statistically significant decrease in fractures and back pain when comparing the alfacalcidol group to the vitamin D3 group. The authors note: "We conclude that alfacalcidol plus calcium is highly superior to plain vitamin D3 plus calcium in the treatment of established GIOP." There are several interesting elements in this study:
1. The very significant osteoporosis in this patient group, yet only some form of vitamin D plus calcium was used to treat the osteoporosis rather than a bisphosphonate or other approved osteoporosis medication.
2. There is a combination of statistical mean and median analyses used in the study. This is unusual with most studies comparing all results using the mean, or average of the group. The median is "The middle most measurement when values are arranged in order of size." Generally, the mean is used when a distribution of the data is fairly symmetrical and the median is used when the distribution of data is highly skewed. I'm not a statistician, but just point out that the use of the median is rare in studies I have evaluated. Whether it taints the results or is perfectly normal, I can't say. My guess is that if you compare mean to mean or median to median, you are O.K. But, comparing mean to median would be flawed. In this study they compared mean starting BMD between pairs, and then compared median final BMD between pairs, so the results should be alright.
3. There was only a median percentage increase of 2.4% in the lumbar spine in the alfacalcidol group after three years of therapy. One would expect that much, or even greater improvement, within one year of therapy on risedronate or alendronate. Three-year rates of fracture of any kind were 19.4% among those treated in the alfacalcidol group compared to 40.65% in the vitamin D3 group, basically a 50% reduction. Yet, the 40% rate of fracture in the vitamin D3 group makes it hard to justify using this therapy when known effective methods of treating osteoporosis existed when the study started. In fact, the 20% fracture rate seems high, too.
4. Note that the authors say that alfacalcidol is superior to vitamin D3, but don't necessarily say it is a superior therapy for osteoporosis. So, let's examine that issue.
Comparison of alfacalcidol with alendronate to treat osteoporosis
Alendronate to treat men with osteoporosis. This German study is also by Ringe JD and others. It is not an exact comparison to the above study because the men didn't have GIOP, they just had osteoporosis. Thus, the results may not be directly comparable, but should be close enough for comfort. What is important in this study is that after three years of therapy, 24.2% of the men on alfacalcidol had fractures (a similar rate to the above study) while only 10.2% of those on alendronate had fractures. This is over a 50% reduction in fractures for the alendronate group compared to the alfacalcidol group. But, what is really significant is that the alendronate group's fracture rate in this study is 50% less than that of the alfacalcidol group in the study above. What that means is that there could be no justification for using alfacalcidol to treat established osteoporosis due to the significant superiority of alendronate when comparing fracture rate reduction.
Discussion. What might be an important finding from the first study is that alfacalcidol could be an important preventive measure for patients on glucocorticoid therapy. Obviously, the goal would be to start therapy before extensive loss of BMD has occurred. With the ability to improve BMD over three years in the osteoporosis group, as noted above, one would expect a similar result would prevent the loss of BMD in patients starting glucocorticoid therapy. As luck would have it there is a study that shows just this result.
Alfacalcidol to prevent glucocorticoid-induced osteoporosis
Prevention rather than treatment of osteoporosis with alfacalcidol. This is a study done in Belgium by Reginster JY and others, and one which I have discussed in a Newsletter previously. In a one-year study with patients who started taking glucocorticosteroids when the study began, the authors found a slight increase (less than 1%) in BMD in the alfacalcidol group and 5.67% decrease in BMD in the placebo group. Thus, alfacalcidol is effective to prevent osteoporosis in patients on glucocorticosteroid therapy. And, although alfacalcidol is also more effective than vitamin D3 over a three-year period, alendronate, or other bisphosphonates, are more effective for treating frank osteoporosis.
Note: For an excellent overview of vitamin D see this University of California, Riverside Website.