Hip Fracture
Conditions
Keywords
Vitamin D, Hip fracture, Optimal level, Deficiency, Functional muscle strength
Brief summary
The purpose of the study is to determine the best dose of Vitamin D to give to hip fracture patients to achieve the optimal therapeutic level.
Detailed description
Low Vitamin D levels can cause faster bone loss and increase the risk of having a fracture. Patients who experience a hip fracture have low levels of Vitamin D. It is not clear how much Vitamin D must be taken in order to reach this optimal level. Serum 25-hydroxyvitamin D3 (25-OHD) concentrations are the recognized functional status indicator for vitamin D. Although there is no clear consensus, vitamin D 'insufficiency' has been considered in the range of 25- 75/80 nmol/L. Patients with acute hip fracture are at high risk for a recurrent hip fracture or other fragility fractures (and falls) and are a group who should be targeted for osteoporosis treatment (i.e. Bisphosphonate or other antiresorptive). Before fracture patients start on a bisphosphonate, however, an important consideration is whether 25-OHD levels are at a therapeutic level (\>75 nmol/l and less than 150-200 nmol/L). Case-control studies indicate that older people who experience a hip fracture have lower serum concentrations of 25-OHD than do those without a fracture. In cross-sectional studies, the majority of patients with hip fracture are considered to have insufficient vitamin D levels. Although the benefits of supplementing patients with at least 800 to 1000 IU/day Vitamin D3 may be recognized, there is little information available to guide physicians regarding the appropriate management of hip fracture patients who may be severely Vitamin D deficient, particularly in acute hip fracture patients. Few studies have examined whether high dose vitamin D (i.e. 50,000 IU or greater/week) offers an advantage over smaller, routinely prescribed doses (i.e. 800 or 1000 IU), particularly in hip fracture patients. The purpose of this study is to determine the number of hip fracture patients reaching an optimal level of vitamin D comparing between three different Vitamin D dose strategies: A. 50,000 D2 oral bolus followed by 800 IU D3 daily B. 100,000 D2 oral bolus followed by 800 IU D3 daily C. 800 IU D3 daily The Vitamin D strategies will be administered over 3-months in acute hip fracture patients. The proportion of patients reaching an optimal level of 25-OHD (\>75 nmol/L) will be determined. Secondary measures include the Timed Up and Go test, and 2 Minute Walk Test to compare the effects of the Vitamin D supplementation strategies on functional and muscle strength scales.
Interventions
DRUGVitamin D2
50 000 IU vitamin D2, one time bolus dose
DRUGPlacebo
Placebo, 1 time bolus dose
Sponsors
Merck Frosst Canada Ltd.
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fragility hip fracture patient * Previous Vitamin D supplementation is okay.
Exclusion criteria
* Patients with pathological fracture secondary to malignancy or intrinsic bone disease (eg. Paget's disease) * Cancer in the past 10 years likely to metastasize to bone * Renal insufficiency (creatinine \<30 mls/min) * Hypercalcemia (primary hyperparathyroidism; granulomatous diseases; drug-induced such as lithium, thiazides), hypocalcemia, hypercalciuria, fracture or stroke within the last 3 months * Hormone replacement therapy, calcitonin, fluoride, or bisphosphonates during the previous 24 months * Pre-existing bone abnormality * Renal stones in past 10 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Creatinine | Baseline | Baseline blood samples were drawn in-hospital. In additional creatinine was accessed at baseline. |
| Alkaline Phosphatase | Baseline | Baseline blood samples were drawn in-hospital. In additional Alkaline Phosphatase was accessed at baseline. |
| Hemoglobin | Baseline | Baseline blood samples were drawn in-hospital. In additional hemoglobin was accessed at baseline. |
| 25-hydroxyvitamin D3 (25-OHD) | Baseline, 4 weeks and 3 months | Serum 25-hydroxyvitamin D3 (25-OHD) was measured at baseline, at discharge from hospital (approximately 4-weeks), and at a follow-up study visit at approximately 3-months.Baseline and 4-week blood samples were drawn in-hospital; venipunctures performed at 3-months were either in-hospital (if patient remained in acute care or rehabilitation) or at the out-patient clinic visit.Serum 25-OHD was analyzed with the DiaSorin, 25-hydroxyvitamin D radioimmunoassay (Stillwater, Minnesota 55082-0285, U.S.A) at the central laboratory with the exception of 3 patients (data analyzed at other laboratories). |
| Parathyroid Hormone (PTH) | Baseline | Baseline blood samples were drawn in-hospital. In additional PTH was accessed at baseline. |
| Calcium | Baseline, 4 weeks | Baseline blood samples were drawn in-hospital. In additional Calcium was accessed at baseline and approximately 4 weeks. |
| Phosphate | Baseline | Baseline blood samples were drawn in-hospital. In additional phosphate was accessed at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months | 3 months | The 2MWT was collected for patients who attended the 3-month clinic appointment by study coordinators or for patients who attended rehabilitation, it was abstracted from their charts. The 2MWT test was given in a carpeted corridor and the subject was instructed to wear regular footwear and to use their customary walking aid. The distance the participant could comfortably walk in two-minutes (without physical assistance) was measured in metres. |
| Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months | 3 months | The Timed Up and Go (TUG) was collected for patients who attended the 3-month clinic appointment by study coordinators or for patients who attended the rehabilitation unit this is routinely collected and was abstracted from chart. The TUG was conducted using a standard armchair and a line marked 3-metres from the chair. Participants were given the following instructions (no physical assistance was given): Rise from the chair, walk to the line on the floor, turn, return to the chair and sit down again. Scores are measured as time in seconds to complete the task. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 000 IU Vitamin D2 50 000 IU Vitamin D2 at beginning of study and 1000IU vitamin D3 for 90 days | 22 |
| 100 000 IU Vitamin D2 100 000 IU Vitamin D2 at beginning of study and 1000IU vitamin D3 for 90 days | 22 |
| Placebo Placebo at beginning of study and 1000IU vitamin D3 for 90 days | 20 |
| Total | 64 |
Baseline characteristics
| Characteristic | 50 000 IU Vitamin D2 | 100 000 IU Vitamin D2 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 82.9 years STANDARD_DEVIATION 8.7 | 73.9 years STANDARD_DEVIATION 12.4 | 78.5 years STANDARD_DEVIATION 10.3 | 78.43 years STANDARD_DEVIATION 11.09 |
| Region of Enrollment Canada | 22 participants | 22 participants | 20 participants | 64 participants |
| Sex: Female, Male Female | 15 Participants | 8 Participants | 13 Participants | 36 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 22 | 0 / 22 | 2 / 20 |
| serious Total, serious adverse events | 1 / 22 | 3 / 22 | 1 / 20 |
Outcome results
Primary
25-hydroxyvitamin D3 (25-OHD)
Serum 25-hydroxyvitamin D3 (25-OHD) was measured at baseline, at discharge from hospital (approximately 4-weeks), and at a follow-up study visit at approximately 3-months.Baseline and 4-week blood samples were drawn in-hospital; venipunctures performed at 3-months were either in-hospital (if patient remained in acute care or rehabilitation) or at the out-patient clinic visit.Serum 25-OHD was analyzed with the DiaSorin, 25-hydroxyvitamin D radioimmunoassay (Stillwater, Minnesota 55082-0285, U.S.A) at the central laboratory with the exception of 3 patients (data analyzed at other laboratories).
Time frame: Baseline, 4 weeks and 3 months
Population: Baseline data (n=59) was missing for two participants, and four outliers with 25-OHD taken at 6, 10 or 12 days were not included. 4-week data (n=50) was missing for 13 participants, and two outliers with 25-OHD taken at \<13 days were not included. 3-month data (n=47) was missing for 18 participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 50 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | 3-month | 84.2 nmol/L |
| 50 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | 4-week | 84.5 nmol/L |
| 50 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | Baseline | 53.5 nmol/L |
| 100 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | 3-month | 73.3 nmol/L |
| 100 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | Baseline | 58.4 nmol/L |
| 100 000 IU Vitamin D2 | 25-hydroxyvitamin D3 (25-OHD) | 4-week | 75.6 nmol/L |
| Placebo | 25-hydroxyvitamin D3 (25-OHD) | 4-week | 69.3 nmol/L |
| Placebo | 25-hydroxyvitamin D3 (25-OHD) | Baseline | 46.7 nmol/L |
| Placebo | 25-hydroxyvitamin D3 (25-OHD) | 3-month | 86.7 nmol/L |
Primary
Alkaline Phosphatase
Baseline blood samples were drawn in-hospital. In additional Alkaline Phosphatase was accessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 000 IU Vitamin D2 | Alkaline Phosphatase | 98.6 U/L | Standard Deviation 3.78 |
| 100 000 IU Vitamin D2 | Alkaline Phosphatase | 78.7 U/L | Standard Deviation 26.2 |
| Placebo | Alkaline Phosphatase | 79.4 U/L | Standard Deviation 51.1 |
Primary
Calcium
Baseline blood samples were drawn in-hospital. In additional Calcium was accessed at baseline and approximately 4 weeks.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 50 000 IU Vitamin D2 | Calcium | Baseline | 2.10 mmol/L | Standard Deviation 0.14 |
| 50 000 IU Vitamin D2 | Calcium | 4 Weeks | 2.26 mmol/L | Standard Deviation 0.17 |
| 100 000 IU Vitamin D2 | Calcium | Baseline | 2.12 mmol/L | Standard Deviation 0.11 |
| 100 000 IU Vitamin D2 | Calcium | 4 Weeks | 2.31 mmol/L | Standard Deviation 0.11 |
| Placebo | Calcium | Baseline | 2.08 mmol/L | Standard Deviation 0.14 |
| Placebo | Calcium | 4 Weeks | 2.28 mmol/L | Standard Deviation 0.15 |
Primary
Creatinine
Baseline blood samples were drawn in-hospital. In additional creatinine was accessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 000 IU Vitamin D2 | Creatinine | 70.5 µmol/L | Standard Deviation 23.8 |
| 100 000 IU Vitamin D2 | Creatinine | 77.4 µmol/L | Standard Deviation 26.1 |
| Placebo | Creatinine | 73.7 µmol/L | Standard Deviation 37 |
Primary
Hemoglobin
Baseline blood samples were drawn in-hospital. In additional hemoglobin was accessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 000 IU Vitamin D2 | Hemoglobin | 102.2 g/L | Standard Deviation 14.3 |
| 100 000 IU Vitamin D2 | Hemoglobin | 107.9 g/L | Standard Deviation 17.4 |
| Placebo | Hemoglobin | 108.6 g/L | Standard Deviation 15.2 |
Primary
Parathyroid Hormone (PTH)
Baseline blood samples were drawn in-hospital. In additional PTH was accessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 000 IU Vitamin D2 | Parathyroid Hormone (PTH) | 5.35 pmol/L | Standard Deviation 3.01 |
| 100 000 IU Vitamin D2 | Parathyroid Hormone (PTH) | 5.10 pmol/L | Standard Deviation 3.91 |
| Placebo | Parathyroid Hormone (PTH) | 4.2 pmol/L | Standard Deviation 2.12 |
Primary
Phosphate
Baseline blood samples were drawn in-hospital. In additional phosphate was accessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 000 IU Vitamin D2 | Phosphate | 0.86 mmol/L | Standard Deviation 0.22 |
| 100 000 IU Vitamin D2 | Phosphate | 0.97 mmol/L | Standard Deviation 0.24 |
| Placebo | Phosphate | 0.94 mmol/L | Standard Deviation 0.27 |
Secondary
Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months
The Timed Up and Go (TUG) was collected for patients who attended the 3-month clinic appointment by study coordinators or for patients who attended the rehabilitation unit this is routinely collected and was abstracted from chart. The TUG was conducted using a standard armchair and a line marked 3-metres from the chair. Participants were given the following instructions (no physical assistance was given): Rise from the chair, walk to the line on the floor, turn, return to the chair and sit down again. Scores are measured as time in seconds to complete the task.
Time frame: 3 months
Population: The number of participants who completed the TUG test is lower than the number of participants who completed the primary outcome at this time point. Not everyone chose to complete the functional TUG test at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 000 IU Vitamin D2 | Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months | 26.2 seconds |
| 100 000 IU Vitamin D2 | Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months | 19.1 seconds |
| Placebo | Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months | 18.1 seconds |
Secondary
Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months
The 2MWT was collected for patients who attended the 3-month clinic appointment by study coordinators or for patients who attended rehabilitation, it was abstracted from their charts. The 2MWT test was given in a carpeted corridor and the subject was instructed to wear regular footwear and to use their customary walking aid. The distance the participant could comfortably walk in two-minutes (without physical assistance) was measured in metres.
Time frame: 3 months
Population: The number of participants who completed the 2WT is lower than the number of participants who completed the primary outcome at this time point. Not everyone chose to complete the functional 2WT test at this time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 000 IU Vitamin D2 | Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months | 60.2 meters |
| 100 000 IU Vitamin D2 | Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months | 80.3 meters |
| Placebo | Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months | 63.4 meters |