Falls: To D or Not to D—That Is Not the (Only) Question!

In their current Annals article, Appel and colleagues (1) report the impact of vitamin D supplementation on falls in community-dwelling older adults. This interesting, innovative trial reinforces some of what we know, highlights what we still do not know, and underscores what we need to learn. Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams. As many as one third of persons aged 65 years and older fall each year, and the consequences may be dire, leading to fractures and other injuries, hospitalization, nursing home admission, and even death. Several studies reported associations between vitamin D status and falls, yet the results of clinical trials of vitamin D supplementation are mixed (2). Appel and colleagues' trial for the STURDY (Study to Understand Fall Reduction and Vitamin D in You) Collaborative Research Group is a National Institutes of Health–funded, multiyear endeavor to determine whether vitamin D₃ supplementation reduces falls in community-dwelling adults aged 70 years and older who are at elevated risk for falls and have serum 25-hydroxyvitamin D [25-(OH)D] levels of 25 to 72.5 nmol/L (1).

In 687 trial participants, just over 70% had either prefrail or frail status (59.4% and 11.8%, respectively) and 55.6% scored 9 points or less on the Short Physical Performance Battery (SPPB), indicating a substantial degree of functional impairment. Falls were recorded in 61.5% of the participants, which—although a very high percentage—is consistent with expected elevated risk given that the trial eligibility criteria required previous falls, gait or balance problems, or use of an assistive device while walking. The dose-finding phase of the study compared 200 versus 1000, 2000, and 4000 IU of vitamin D₃ per day. Participants assigned to the 2000- and 4000-IU groups had a statistically significantly greater risk for hospitalization or death than the 200-IU group (hazard ratios, 2.69 and 1.68, respectively). Those participants were then switched to 1000 IU/d. The 1000-IU group had fewer falls than both the 2000- and 4000-IU groups (hazard ratios, 0.65 and 0.71, respectively), but ultimately the researchers found no difference between the 1000- and 200-IU groups. These data reveal no benefit from higher-dose vitamin D supplementation and even raise concerns that high doses may have deleterious effects (1).

Several limitations of the trial warrant consideration. First, control group participants received 200 IU of vitamin D₃ to ensure that their average total daily vitamin D intake (dietary plus supplementary) reached the recommended daily allowance of approximately 800 IU. Over the time of the study, serum 25-(OH)D levels increased in all groups, including the 200 IU control population, which exhibited an average of 55.4 nmol/L at baseline and 70.4 nmol/L at 24 months. Intervention groups exhibited an average of 55 to 57 nmol/L at baseline and approximately 89 to 99 nmol/L at end point. It appears that 25-(OH)D measurements were obtained in only approximately half the participants at end point. Participants with lower baseline 25-(OH)D levels (25 to 48.5 nmol/L) who received vitamin D supplementation experienced no greater amount of falls than those with higher initial serum levels. However, both groups were compared against the 200 IU control, which—as noted earlier—exhibited increases in serum 25-(OH)D levels. Overall, the trial was a well-executed effort to determine whether high-dose vitamin D supplementation prevents falls. The investigators' commitment to “first do no harm” by providing the control group with 200 IU of vitamin D per day is commendable, but does this strategy prevent the modeling of real-world scenarios—such as frank vitamin D deficiency—in which community-dwelling older adults might realize benefits? The answer is important because older adults with greater insufficiency or frank deficiency, particularly those with 25-(OH)D levels of 25 nmol/L or less (2), may be those most likely to benefit from vitamin D supplementation.

We also lack information on participants' comorbid medical conditions, medications that increase fall risk, and the methods used to assess cognitive impairment and frailty. Analyses of patient subgroups on the basis of these characteristics, as well as the SPPB score, might provide insight into the possible detrimental effects of the higher vitamin D doses. However, there were no statistically significant differences in the lack of benefit of supplementation between the subgroups. Furthermore, the 2-year timeframe may have been inadequate to observe longer-term benefit (3). An animal model of vitamin D insufficiency revealed declines in physical performance over the human equivalent of 30 years or longer (4).

What do we still need to know? Although other studies have also suggested that higher-dose supplementation does not provide benefit and might actually be harmful (5-7), the doses used in this study are within the safety recommendations of the National Academy of Medicine. Many adults are consuming 2000 or 4000 IU daily. Are these amounts truly harmful? The VITAL (Vitamin D and Omega-3 Trial) investigators found no reduction in falls with 2000 lU/d over 5 years in community-dwelling older adults who were not, on average, vitamin D insuf-ficient, but supplementation did not result in harms (8). The remaining question is, how can we prevent falls? The answer almost certainly will entail multicomponent approaches that include medication management, assessment of cognition and orthostatic blood pressure, exercise or physical therapy, disease management, vision care, home safety modifications, and possibly even vitamin D supplementation for certain patients. Disappointingly, several recent community-based trials that sought to reduce falls in the primary care setting have come up short (9, 10). We also need to know more about whether and to what extent vitamin D status and exercise interact.

So, to D or not to D? That may still be a question. But perchance ‘tis nobler to embrace the slings and arrows of falls and subsequent injuries by taking arms against a sea of contributing risk factors. In other words, we still need additional creative clinical trials using interdisciplinary strategies to oppose the major burden that falls place on older adults and the health care system and better strive to enhance functional capacity, healthspan, and quality of life.