Vitamin D supplementation following hip fracture: what is the best dosing strategy?
How to Cite
OrthoEvidence. Vitamin D supplementation following hip fracture: what is the best dosing strategy? . ACE Report. 2014;3(3):22. Available from: https://myorthoevidene.com/AceReport/Report/4659
A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementationBMC Musculoskelet Disord. 2011 Jun 20;12:135. doi: 10.1186/1471-2474-12-135
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65 patients who had recently suffered an acute hip fracture were randomized to determine the effect of a vitamin D2 loading dose on serum 25-hydroxyvitamin D3 (25-OHD) levels. Patients were allocated to receive one of three loading doses on top of vitamin D3 supplementation: either a high-loading dose (100000 IU), a low-loading dose (50000 IU), or a placebo loading dose. Results after 3 months indicated that there was no significant effect of either active loading dose on serum 25-OHD levels.
Was the allocation sequence adequately generated?
Was allocation adequately concealed?
Blinding Treatment Providers: Was knowledge of the allocated interventions adequately prevented?
Blinding Outcome Assessors: Was knowledge of the allocated interventions adequately prevented?
Blinding Patients: Was knowledge of the allocated interventions adequately prevented?
Was loss to follow-up (missing outcome data) infrequent?
Are reports of the study free of suggestion of selective outcome reporting?
Were outcomes objective, patient-important and assessed in a manner to limit bias (ie. duplicate assessors, Independent assessors)?
Was the sample size sufficiently large to assure a balance of prognosis and sufficiently large number of outcome events?
Was investigator expertise/experience with both treatment and control techniques likely the same (ie.were criteria for surgeon participation/expertise provided)?
Yes = 1
Uncertain = 0.5
Not Relevant = 0
No = 0
The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.
Inclusion / Exclusion
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65
The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.
Why was this study needed now?
Hip fracture patients are usually found to have insufficient levels of 25-hydroxyvitamin D3 (25-OHD), which has been demonstrated to have important implications in falls and fractures. A number of analyses have suggested that 800 to 1000 IU/day vitamin D3 supplementation can reduce falls and fractures, and are also consistently reduced when 25-OHD levels are at least 75nmol/L; however there has yet to be consensus on the optimal dosing strategy in these patients. This study aimed to evaluate the change in 25-OHD levels with a loading dose of vitamin D2 on top of daily supplementation with vitamin D3.
What was the principal research question?
Was there a difference in serum 25-OHD levels of acute hip fracture patients who received either a high, low or placebo loading dose of vitamin D2, combined with daily vitamin D3 supplementation, when measured over 3 months?
What were the important findings?
- Some baseline measurements of 25-OHD levels were taken after bolus administration of vitamin D2 or placebo; 25 patients (n=11, 6, and 8 for placebo, 50 000, and 100 000 groups, respectively) had serum collection 1-3 days after bolus. Measurements of 25-OHD levels in this time frame were 41.6nmol/L in the placebo group, 59.0nmol/L in the 50 000 IU group, and 76.0nmol/L in the 100 000 IU group (p=0.03), resulting in significant difference between the placebo and 100 000 group (post-hoc).
- Baseline measurement of 25-OHD levels in 34 patients (n=7, 14, and 13 for placebo, 50 000 IU, and 100 000 IU groups, respectively) prior to bolus were 58.7nmol/L in the placebo, 52.3nmol/L in the 50 000 IU, and 44.3nmol/L in the 100 000 IU group (p=0.39).
- Adjustment for time between bolus dose and 25-OHD measurement resulted in non-significant difference between groups (46.7nmol/L placebo, 53.5nmol/L 50 000 IU, 58.4nmol/L 100 000 IU; p=0.37).
- Mean 25-OHD levels at 4-week follow up were 69.3nmol/L in the placebo group, 84.5nmol/L in the 50 000 IU group, and 75.6nmol/L in the 100 00 IU group (p=0.15), with proportion of patients above 75nmol/L level at 47.1%, 58.8%, and 50.0% in the groups, respectively (p=0.76).
- No significant difference was observed between groups at 3 months, with 25-OHD levels at 86.7nmol/L in the placebo group, 84.2nmol/L in the 50 000 IU group, and 73.3nmol/L in the 100 000 IU group (p=0.09). Proportion of patients above 75nmol/L level in the 100 000 IU was 44.4%, compared to 76.5% and 75.0% in the placebo and 50 000 IU groups, respectively. This difference, however, was found to be not statistically significant (p=0.09).
- A total of 5 serious adverse events were reported: 2 deaths, 1 fractured hip, 1 pulmonary edema and myocardial infarction, and 1 gangrenous foot (which was amputated). One occurred in the placebo group and 2 each in the 50 000 IU and 100 000 IU groups. All were deemed not related to the study treatments.
What should I remember most?
One-time bolus loading-doses of either 50 000 IU and 100 000 IU vitamin D2 prior to 90-day supplementation of 1000 IU/day vitamin D3 did not significantly increase 25-OHD levels over 3 months, nor the proportion of patients who presented with 25-OHD levels above 75nmol/L.
How will this affect the care of my patients?
The findings of this study suggest that an additional loading-dose of vitamin D2 does not increase 25-OHD levels compared to daily supplementation of vitamin D3 alone. It would be worthwhile to conduct an investigation into the effect of a vitamin D3 loading-dose along with daily supplementation, as it has been suggested that vitamin D3 is more efficiently metabolized in human physiology. Nonetheless, supplementation should be complimented with a safety analysis considering incidence of hypercalcemia.
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