Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial

Reid, Ian R.; Horne, Anne; Mihov, Borislav; Gamble, Gregory D.; Al-Abuwsi, F.; Singh, Manisha; Taylor, Lynne; Fenwick, Sheryl; Camargo, Carlos A.; Stewart, Alistair; Scragg, Robert

doi:10.1111/joim.12651

Cited by 106 publications

(91 citation statements)

References 23 publications

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“…I agree with the authors that the study is highly valuable towards a trial-based definition of vitamin D deficiency regarding bone health in generally healthy older adults [1] and would also like to discuss their important findings from a different point of view to clarify the current confusion over the use of vitamin D and/or calcium supplements.High-dose vitamin D supplementation partially prevented an age-related decrease in areal BMD but did not result in an increase in areal BMD; mean baseline levels of circulating 25-hydroxyvitamin D in the placebo and vitamin D groups were 56 and 55 nmol L …”

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confidence: 67%

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confidence: 67%

“…, respectively, and significant treatment effects were detected in the total hip and femoral neck (both less than 1%) but not the lumbar spine or total body [1]. This is consistent with a recent meta-analysis of a total of 33 randomized clinical trials including more than 50 000 community-dwelling men and women older than 50 years that investigated the effects of calcium, vitamin D or calcium plus vitamin D supplements versus a placebo or no treatment on fracture risk [2].…”

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confidence: 93%

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Vitamin D and bone health: key involvement of physical activity

Sugiyama

2018

J Intern Med

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In a recent substudy of the randomized, doubleblind, placebo-controlled ViDA trial that included a total of 452 community-dwelling older adults (placebo group: n = 224, mean age 68.6 years, 65% male; vitamin D group: n = 228, mean age 69.0 years, 62% male), Reid et al.[1] investigated effects of monthly high-dose (100 000 IU) vitamin D 3 supplementation for 2 years on areal bone mineral density (BMD) in the lumbar spine, total hip, femoral neck and total body. I agree with the authors that the study is highly valuable towards a trial-based definition of vitamin D deficiency regarding bone health in generally healthy older adults [1] and would also like to discuss their important findings from a different point of view to clarify the current confusion over the use of vitamin D and/or calcium supplements.High-dose vitamin D supplementation partially prevented an age-related decrease in areal BMD but did not result in an increase in areal BMD; mean baseline levels of circulating 25-hydroxyvitamin D in the placebo and vitamin D groups were 56 and 55 nmol L À1, respectively, and significant treatment effects were detected in the total hip and femoral neck (both less than 1%) but not the lumbar spine or total body [1]. This is consistent with a recent meta-analysis of a total of 33 randomized clinical trials including more than 50 000 community-dwelling men and women older than 50 years that investigated the effects of calcium, vitamin D or calcium plus vitamin D supplements versus a placebo or no treatment on fracture risk [2]. The meta-analysis showed no significant associations between the use of these supplements and the incidence of hip fracture as well as nonvertebral, vertebral or total fractures, even in subgroups with lower than 50 nmol L À1 of serum 25-hydroxyvitamin D levels at baseline, dietary intake with lower than 900 mg day À1 of calcium or supplementation with higher than 800 IU day À1 of vitamin D and higher than 1000 mg day À1 of calcium. Consequently, in generally healthy older adults, there seems to be little causal relationship of vitamin D status with musculoskeletal outcomes such as areal BMD in contrast to the results from many observational studies. Areal BMD in the hip was, for example, more than 10% lower in older women with serum 25-hydroxyvitamin D levels below 30 nmol L À1 versus above 80 nmol L À1 during the sunny summer season in a population-based cohort [3], whereas high-dose vitamin D supplementation only prevented the age-related decrease in areal BMD in the hip by around 2% in older adults with less than 30 nmol L À1 of serum 25-hydroxyvitamin D levels at baseline although its levels during the supplementation were over 80 nmol L À1 [1]. Accumulating experimental evidence indicates that vitamin D affects the skeleton mainly by controlling calcium absorption in the intestine, which is unlikely to support further cumulative effects with vitamin D supplementation longer than two years because a meta-analysis suggests that calcium supplements or increasing calcium intake can have smal...

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Vitamin D and bone health: key involvement of physical activity

Sugiyama

2018

J Intern Med

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“…The Vitamin D Assessment study (ViDA) in 5100 healthy subjects, aged > 50 years, recently reported that 100,000 IU oral vitamin D 3 monthly was neutral for the prevention of CV disease [49,50], with a low rate of 25[OH]D deficiency in participants (25%), a lower than expected endpoint rate and monthly doses cited as possible reasons [51]. Metaanalysis and data from ViDA and other studies describe that benefits on clinical outcomes are greatest in the most deficient, and in studies using daily dosing regimens (as in VINDICATE) rather than monthly [52][53][54][55].…”

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Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

et al. 2018

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“…calcium intake) and individual bioavailability of 25-hydroxyvitamin D by genetically determined concentrations of vitamin D-binding protein [4,10,11]. Dr Sugiyama mentioned the ViDA study (a randomized clinical trial) as evidence of absence of vitamin D effect, but a recent publication from that trial indicated that there exist beneficial effects on BMD with vitamin D supplementation if S-25OHD is below 30 nmol L À1 measured by the gold standard method LC-MS/MS [12]. This might be an accurately determined threshold, but more such studies are needed.…”

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Response to ‘Letter to the Editor’ regarding the article ‘The seasonal importance of serum 25‐hydroxyvitamin D for bone mineral density in older women’

Michaëlsson

Melhus

2017

J Intern Med

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Response to 'Letter to the Editor' regarding the article 'The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women' Dear Sir, We thank Dr Sugiyama for his thoughts regarding our publication [1]. These comments mainly deal with differences in physical activity as an underlying explanation for our findings and a null effect on BMD with vitamin D supplementation in metaanalyses of RCTs. We agree that a more accurate definition of true vitamin D deficiency is needed. At what concentrations of serum 25-hydroxyvitamin D (S-25OHD) should physicians recommend supplementation?The response from Dr Sugiyama indicates a conservative approach but very low concentrations of S-25OHD inevitably do lead to rickets and osteomalacia. The dramatic effects of vitamin D treatment on BMD in these (vitamin D deficiency) diseases cannot be explained by physical activity. On the other hand, without stringent indications, that is supplementing those without true deficiency, there is a legitimate fear that vitamin D supplementation might actually cause net harm [2,3]. The report from the Institute of Medicine [4] also emphasized that there may be risks from both low and high levels of vitamin D and that there may be a Ushaped curve of risk, 'which has been seen with many other nutrients as well ' [4]. We showed a clear seasonal variation for the importance of S-25OHD on bone mineral density (BMD) in women [5]. Our results are in agreement with at least 40 nmol/L measured by LC-MS/MS for optimal bone health if the blood sample is drawn during summer whilst those with a low S-25OHD during winter were not, on average, at higher risk of osteoporosis. Our observational design is indeed a major limitation, but differences in leisure time physical activity are nonetheless unlikely to have distorted our results. We did, in fact, adjust our results for differences in reported physical activity levels without major influences on our estimates. Have they existed, as an explanation, such differences in physical activity would also be observed in women during winter time, but during that season, we did not find any major difference in BMD dependent on S-25OHD status. Nota bene, differences in risk factor patterns between those with low and those with higher S-25OHD were similar during summer and during winter (including no major dissimilarities in physical activity). Moreover, physical exercise in older women provides only modest positive effects on bone accrual [6-8] -effects on BMD much smaller than those observed by us.A thorough meta-analysis from Ian Reid's research group displayed on average no major effect of vitamin D supplementation on bone mineral density [9]. No effect modification by higher dose, duration of treatment or low baseline 25-hydroxyvitamin D levels (<50 nmol L À1 as suggested by Institute of Medicine [4]) was noted. The problem is, however, differences in assay performances of the studies included in the meta-analysis, seasonal variation, fat mass, nutritional status (e.g. calcium intake) and ...

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Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial

Cited by 106 publications

References 23 publications

Vitamin D and bone health: key involvement of physical activity

Vitamin D and bone health: key involvement of physical activity

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

Response to ‘Letter to the Editor’ regarding the article ‘The seasonal importance of serum 25‐hydroxyvitamin D for bone mineral density in older women’

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