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

• ClinicalTrials.gov Identifier: NCT00424619
• Recruitment Status: Completed
• First Posted: January 19, 2007
• Results First Posted: June 14, 2012
• Last Update Posted: June 14, 2012
• Sponsor: Hamilton Health Sciences Corporation
• Collaborator: Merck Frosst Canada Ltd.
• Information provided by (Responsible Party): Alexandra Papaioannou, McMaster University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hip Fracture	Drug: Vitamin D2; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomised, Controlled Comparison of Vitamin D Strategies is Acute Hip Fracture Patients
• Study Start Date: October 2007
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 25-hydroxyvitamin D3 (25-OHD) [ Time Frame: 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).
2. Parathyroid Hormone (PTH) [ Time Frame: Baseline ]
   Baseline blood samples were drawn in-hospital. In additional PTH was accessed at baseline.
3. Calcium [ Time Frame: Baseline, 4 weeks ]
   Baseline blood samples were drawn in-hospital. In additional Calcium was accessed at baseline and approximately 4 weeks.
4. Phosphate [ Time Frame: Baseline ]
   Baseline blood samples were drawn in-hospital. In additional phosphate was accessed at baseline.
5. Alkaline Phosphatase [ Time Frame: Baseline ]
   Baseline blood samples were drawn in-hospital. In additional Alkaline Phosphatase was accessed at baseline.
6. Hemoglobin [ Time Frame: Baseline ]
   Baseline blood samples were drawn in-hospital. In additional hemoglobin was accessed at baseline.
7. Creatinine [ Time Frame: Baseline ]
   Baseline blood samples were drawn in-hospital. In additional creatinine was accessed at baseline.

Secondary Outcome Measures :

1. Functional Assessment Using the Timed Up and Go (TUG) Test After 3 Months [ Time Frame: 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.
2. Functional Assessment Using the Two Minute Walk Test (2MWT)After 3 Months [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Hamilton Health Sciences Corporation

Merck Frosst Canada Ltd.

Investigators

• Principal Investigator: Alexandra Papaioannou, M.D., M.Sc.; McMaster University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Alexandra Papaioannou, Dr. Alexandra Papaioannou, McMaster University
• ClinicalTrials.gov Identifier: NCT00424619
• Other Study ID Numbers: 06-449; P1975
• First Posted: January 19, 2007
• Results First Posted: June 14, 2012
• Last Update Posted: June 14, 2012
• Last Verified: May 2012

Keywords provided by Alexandra Papaioannou, McMaster University:

Vitamin D; Hip fracture; Optimal level; Deficiency; Functional muscle strength

Additional relevant MeSH terms:

Fractures, Bone; Hip Fractures; Wounds and Injuries; Femoral Fractures; Hip Injuries; Leg Injuries; Vitamin D; Ergocalciferols; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents