Vitamin D in elderly and BMD

A trial of monthly high-dose vitamin D in community-dwelling older adults found that there were meaningful benefits in bone mineral density in those who had a baseline low vitamin D level (see doi: 10.1111/joim.12651).

Details:
-- a 2 year substudy of a trial in older community-dwelling adults in New Zealand assessed the influence of vitamin D on bone mineral density (BMD) overall, as well as in those with a low 25-OH vitamin D level
-- 452 people were randomized to monthly high-dose vitamin D supplementation (100,000 IU of vitamin D3) vs placebo
-- the primary endpoint was a change in the lumbar spine BMD, with exploratory analyses to see if there was a threshold of baseline 25-OH vitamin D level affecting the BMD

Results:
-- overall, vitamin D supplementation had no significant treatment effect on the lumbar spine or total body, but BMD loss at the hips was significantly attenuated by -1/2% over 2 years in the vitamin D group (?clinical significance of this 1/2% change)
-- there was a significant interaction between baseline 25-OH vitamin D and treatment effect (p=0.04)

    -- in those with baseline 25-OH vitamin D <30 nmol/L (12 ng/ml), there was essentially no change in BMD in the spine and femoral sites in those on vitamin D vs 2-3% worse in those on placebo.

    --when 25-OH vitamin D levels were > 30 mmol/, the difference was about 1/2% (much less than those <30 nmol/L) and significant only at the hip

    --there was no effect on total body BMD (which reflects more cortical bone: this is less likely to change since it is less metabolically responsive than trabecular bone; trabecular bone is more prominent in the spine and hip). 

Commentary:
-- several prior vitamin D supplementation studies did not find benefit on bone density, but some of the large ones did not have baseline 25-OH vitamin D levels checked or they were not so low. This study, not surprisingly, did find those with more severe vitamin D deficiency realized benefit: we know that vitamin D is essential to bone health and that patients with osteomalacia do clearly benefit from vitamin D supplementation, so not so surprising that there is some cutpoint below which repleting vitamin D has real benefit for bones.
--there are vitamin D receptors throughout the body, not just bone. For example, there are receptors affecting the immune system, associations with cancer, hypertension/heart disease..... For example, a small study (see http://gmodestmedblogs.blogspot.com/2012/09/vitamin-d-and-tb-treatment.html ) found that in patients with active TB infection, high dose vitamin D led to faster sputum smear conversion by 2 weeks and faster resolution of inflammatory cytokines/ improvement in markers of immune function. Another small study in India found similar results (see Nursyam EW. Acta Med Indones. 2006; 38(1):3). I will also be sending out a vitamin D blog soon on the pretty strong, consistent relationship between vitamin D and multiple sclerosis tomorrow.
--so, one concern about the current study is that they are looking at the effect of vitamin D only on bone health (which is the effect most uniformly accepted as being clinically related to vitamin D deficiency). But there are a slew of other conditions associated with vitamin D, as noted above, and if there is indeed a causal relationship, there may be a different cutpoint for clinical benefit of 25(OH) D levels than the 30 nmol/L found here for bone. For more details on the non-bone relationships with vitamin D, see Endocrine Society Clinical Practice Guideline: doi: 10.1210/jc.2011-0385, or a 2014 BMJ review: https://doi.org/10.1136/bmj.g2035)

so, this study adds the following to our understanding of the effects of vitamin D deficiency:

--it is likely that there is no overall bone benefit to just asking everyone to take vitamin D, though targeting those with low vitamin D baseline levels seems to be useful (and adherence to taking vitamin D may also be higher if the individual patient is told that they specifically have vitamin D deficiency vs just a broadcast message to all)

--it is clear that profound vitamin D deficiency, leading to high levels of PTH and osteomalacia, does respond to vitamin D replacement (though the BMD may not return to normal levels)

--doing targeted screening of individuals does make sense, eg those at higher risk (little sunlight exposure, especially in northern climates with less effective sunlight to produce vitamin D), as well as in darker skin patients or older ones (both do not make as much vitamin D as lighter skin or younger people).  But, for what it's worth, my own experience is that I have been a pretty poor predictor as to which of my patients have really low vs okay vitamin d levels just based on my sense of their risk (eg, i have actually been testing 25(OH) D levels pretty regularly for 15-20  years, and some patients I thought were at pretty low risk of vitamin D deficiency actually had undetectable levels....). 

so, this study above confirms that there is a threshold effect here (at least for bone), which in their assessment was a 25-OH vitamin D level of about 30 nmol/L (12 ng/ml). It should be pointed out that the USPSTF in their document of 2014 does not feel that there is sufficient evidence "to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults", and specifically community-dwelling, nonpregnant adults >18yo. But, unlike other micronutrients, vitamin D depends not so much on foods (other than some specifically supplemented) but more on sun exposure and the ability of the skin to produce vitamin D. so, eating healthfully and exercising regularly indoors does not help so much. and, if there really is some benefit, checking a blood level and giving this really cheap supplement has little harm and potentially significant benefit....

prior blogs: (there are lots; go to http://blogs.bmj.com/bmjebmspotlight/?s=vitamin+d&submit=Search . will list a few below which had some unexpected results:

http://blogs.bmj.com/bmjebmspotlight/2017/05/01/primary-care-corner-with-geoffrey-modest-md-statin-myopathy-and-vitamin-d-deficiency/​ found that statin myopathy was more common in those vitamin D deficient, and that in most cases it resolved by repleting vitamin D

http://blogs.bmj.com/bmjebmspotlight/2016/01/06/primary-care-corner-with-geoffrey-modest-md-migraine-prophylaxis-with-simvastatinvitamin-d/ found that simvastatin plus vitamin D decreased migraine frequency

http://blogs.bmj.com/bmjebmspotlight/2015/05/12/primary-care-corner-with-geoffrey-modest-md-vitamin-d-and-atopic-dermatitis-in-kids/​  found that repleting vitamin D levels in kids who are deficient led to improvement in atopic dermatitis