A Randomised, Controlled Comparison of Vitamin D Strategies is Acute Hip Fracture Patients

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.

Study Overview

• Status: Completed
• Conditions: Hip Fracture
• Intervention / Treatment: Drug: Vitamin D2; Drug: Vitamin D2; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; Placebo	Drug: Placebo; Placebo, 1 time bolus dose
Active Comparator: 1; 50 000 IU Vitamin D2	Drug: Vitamin D2; 50 000 IU vitamin D2, one time bolus dose; Other Names: Ostoforte; Drug: Vitamin D2; 100 000 IU vitamin D2, one time bolus dose; Other Names: Ostoforte
Active Comparator: 2; 100 000 IU Vitamin D2	Drug: Vitamin D2; 50 000 IU vitamin D2, one time bolus dose; Other Names: Ostoforte; Drug: Vitamin D2; 100 000 IU vitamin D2, one time bolus dose; Other Names: Ostoforte

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline, 4 weeks and 3 months
Parathyroid Hormone (PTH)	Baseline blood samples were drawn in-hospital. In additional PTH was accessed at baseline.	Baseline
Calcium	Baseline blood samples were drawn in-hospital. In additional Calcium was accessed at baseline and approximately 4 weeks.	Baseline, 4 weeks
Phosphate	Baseline blood samples were drawn in-hospital. In additional phosphate was accessed at baseline.	Baseline
Alkaline Phosphatase	Baseline blood samples were drawn in-hospital. In additional Alkaline Phosphatase was accessed at baseline.	Baseline
Hemoglobin	Baseline blood samples were drawn in-hospital. In additional hemoglobin was accessed at baseline.	Baseline
Creatinine	Baseline blood samples were drawn in-hospital. In additional creatinine was accessed at baseline.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months
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.	3 months

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Merck Frosst Canada Ltd.
• Investigators: Principal Investigator: Alexandra Papaioannou, M.D., M.Sc., McMaster University

Publications and helpful links

General Publications

• Papaioannou A, Kennedy CC, Giangregorio L, Ioannidis G, Pritchard J, Hanley DA, Farrauto L, DeBeer J, Adachi JD. A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementation. BMC Musculoskelet Disord. 2011 Jun 20;12:135. doi: 10.1186/1471-2474-12-135.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (Estimate): January 19, 2007

Study Record Updates

• Last Update Posted (Estimate): June 14, 2012
• Last Update Submitted That Met QC Criteria: May 11, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin D; Deficiency; Hip fracture; Optimal level; Functional muscle strength
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 06-449; P1975