Vitamin D supplements with or without calcium to prevent fractures

Abstract

Vitamin D deficiency is associated with fractures. This relationship is biologically plausible. The results of 19 randomized clinical trials with vitamin D with or without calcium show varying results: a decreased fracture incidence in 7, neutral in 10 trials, whereas 2 trials with a high dose of vitamin D once per year showed an increased fracture incidence. In three out of four well-powered trials that used recommended doses of vitamin D 700-1000 IU per day, vitamin D supplementation did not significantly influence fracture risk. In one of these trials, a statistically significant fracture reduction was observed in nursing home residents having severe vitamin D deficiency, low calcium intake and good compliance. Thirteen meta-analyses were done, and 11 of these showed a significantly decreased fracture incidence in the supplemented groups. Vitamin D alone was not effective, studies combining vitamin D and calcium showed inconsistent results. Analyses for vertebral fractures were negative in all cases. In conclusion, a vitamin D supplement of 800 IU per day in combination with calcium may decrease the incidence of non-vertebral fractures, especially in persons in the older age groups having low-baseline vitamin D status and low calcium intake and showing good compliance.

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…Numerous clinical trials and meta-analyses have therefore been performed to investigate the effect of vitamin D supplementation with or without calcium on fracture incidence. In general, the effect of vitamin D alone compared with placebo had no effect on fracture risk, whereas meta-analyses on the combination of vitamin D and calcium were inconclusive showing a 12-26% reduction in fracture risk in some meta-analyses, but no effect in others (264). Several factors may explain these inconsistencies.…”

“…Below 10 ng/ml 25OHD there is a deficit in substrate leading to lower serum1,25(OH) 2 D levels and a decrease in intestinal calcium absorption (325). Extensive clinical experience and some randomized control trials indicate that daily intake of 400 IU vitamin D 3 is sufficient to prevent this type of rickets in children (55,264). In adults, clinical vitamin D-related osteomalacia is usually found in individuals with low sun exposure or in patients with impaired intestinal vitamin D absorption as part of intestinal fat malabsorption, like after bariatric surgery or with inflammatory bowel disease (395).…”

Vitamin D signaling in calcium and bone homeostasis: A delicate balance

“…4). This conclusion is based on several cross-sectional and long-term observational studies as reviewed in more than 14 meta-analyses [6,43,55]. These data however do not prove causality as a low vitamin D status may also be related to osteoporosis and fractures due to unrelated confounding factors or "reverse causality", i.e.…”

“…In these children with vitamin D deficiency, the serum concentrations of 25-hydroxyvitamin D (25OHD) are usually well below 10 (and mostly below 5) ng/ml, in line with the threshold for 25OHD needed for active intestinal calcium absorption [6,42]. To prevent this type of rickets in children, it is generally accepted that daily intake of about 400 IU (10 ug) of vitamin D 3 is sufficient, as supported by extensive clinical experience and some randomized controlled trials (RCTs) [6,43]. There is less agreement on the use of vitamin D supplementation in pregnant or lactating mothers to prevent rickets in their offspring as only very high doses of vitamin D are able to increase the concentration of vitamin D in mother's milk [44].…”

Dairy products and bone health: how strong is the scientific evidence?

“…Most RCT compared vitamin D-fortified with unfortified dairy products in participants with a high vitamin D status, and therefore we cannot conclude whether vitamin D added to dairy products is more beneficial for bone health. However, several meta-analyses (71,72) that showed that the combination of Ca and vitamin D is better than either of them alone underscore the importance of dairy products as a vehicle for vitamin D fortification. In general, further study on bone health is needed in other ethnicities than Chinese and Caucasians, and in men.…”