Clinical trial NCT02047864: Effect of Creatine Supplementation and Exercise on Bone Health
Official title: Long-term Effects of Creatine Supplementation and Exercise Training on Bone Mineral Density and Bone Strength in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoporosis
Sarcopenia
Keywords: Osteoporosis
Sarcopenia
Strength
Bone
Muscle
Creatine
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2014-01-28
Enrollment: 237
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Osteoporosis is an important health problem, costing the Canadian health care system over $2 billion per year. Loss of bone mineral and bone fragility is especially prevalent in postmenopausal women. Of all osteoporotic fractures, hip fractures are the most traumatic. Creatine monohydrate is a nutritional supplement that is often combined with strength training to increase strength and muscle mass. The investigators recently completed a pilot study in a small number of postmenopausal women (n=33) that showed that creatine monohydrate significantly improved hip bone mineral density during a 1-year resistance training program. In our current proposal the investigators want to determine whether creatine combined with strength training can have an even larger effect on bone mineral density at the hip if given over 2 years in a large group of postmenopausal women (n=240). The investigators also want to determine whether this leads to reduced fractures in these women for up to a year after completing the creatine and strength training program.

Detailed description: Age-related bone and muscle loss is a major risk factor for falls, injuries, and fracture and, as Canada's population is aging, prevalence of such health concerns is escalating. Osteoporosis alone is estimated to cost the Canadian health care system $2.3 billion per year or 1.3%, of Canada's total healthcare budget. Postmenopausal women are at high risk of osteoporosis and experience the highest rate of hip fracture, resulting in disability, loss of physical function and premature death. The investigators' study aims to improve bone mass and bone strength at the most clinically relevant bone site, the femoral neck, in order to reduce the risk of hip fracture. Specifically, it will determine the effects of a nutritional supplement (creatine monohydrate) combined with exercise training on bone mineral density (BMD) at the proximal femur in postmenopausal women. .

Creatine monohydrate is found in small amounts in meats and fish and, when taken as a nutritional supplement, increases muscle mass and strength. The investigators have conducted a number of preliminary studies showing that when a creatine supplement is taken during a resistance training program, urinary markers of bone resorption (i.e. bone catabolism) are reduced compared to placebo. The investigators recently completed a small 12-month randomized controlled trial in 33 postmenopausal women who either supplemented with creatine monohydrate (10 g/d) or placebo during a resistance training program. Bone mineral density of the femoral neck decreased by 0.5% in the creatine group, and 3.9% in the placebo group (p\<0.05 between groups). This proposed randomized controlled trial will replicate the investigators' pilot design for longer duration (i.e. 2 years) to determine if sustained supplementation with creatine monohydrate combined with exercise training can induce a clinically significant difference in bone mineral density at the femoral neck (the investigators estimate a 5% difference between creatine and placebo groups capable of predicting a significant reduction in fracture risk).

This trial will use a randomized, double blind, placebo controlled, parallel group, repeated measures design, performed at the Universities of Saskatchewan and Regina. Post-menopausal women (n=240) will be randomized to creatine (10g/d) or placebo groups while participating in an exercise program (resistance training and walking) three times per week for 24 months. The investigators' main dependent variable is femoral neck bone mineral density, which will be assessed at baseline, 12, and 24 months. Secondary variables to be assessed at the same time points include geometric properties of the proximal femur (predictors of bone strength), lumbar spine bone mineral density, ultrasound measurements of bone at the distal radius and tibia (predictive of the architectural integrity of bone), lean tissue mass, muscular strength, dynamic balance, and gait speed. The investigators will assess incidence of falls and fractures at the same time points and also at 12 months post-intervention (i.e. at 36 months). The results of this study have clinical potential, providing physicians and health-care professionals evidence-based advice to give to postmenopausal women interested in taking creatine as a novel strategy to increase bone mineral density and prevent osteoporosis.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women
* Low or moderate risk of fracture

Exclusion Criteria:

* High risk of fracture
* Have taken any bone-altering drugs within the previous 12 months
* Have taken creatine monohydrate in the previous 12 months
* Currently taking systemic corticosteroids
* Have Crohn's Disease or Cushings Disease
* Have severe osteoarthritis

Primary outcomes:
measure: Change from baseline in femoral neck bone mineral density
timeFrame: baseline, 12 months, 24 months
Secondary outcomes:
measure: Change from baseline in total hip bone mineral density
timeFrame: baseline, 12 months, 24 month
measure: Change from baseline in trochanter bone mineral density
timeFrame: baseline, 12 months, 24 month
measure: Change from baseline in Wards bone mineral density
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline in lumbar spine bone mineral density
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline in whole body bone mineral density
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline in hip geometric properties
timeFrame: baseline, 12 months, 24 months
measure: Change in radius speed of sound
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline in tibial speed of sound
timeFrame: Baseline, 12 months, 24 months
measure: Change from baseline in lean tissue mass
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline in squat maximal strength
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline for chest press strength
timeFrame: baseline, 12 months, 24 months
measure: Change from baseline for dynamic balance
timeFrame: Baseline, 12 months, 24 months
measure: Change from baseline for walking speed
timeFrame: Baseline, 12 months, 24 months
measure: Number of falls
timeFrame: 12, 24, and 36 months
measure: Number of fractures
timeFrame: 12, 24, and 36 months
measure: Changes from baseline in blood markers of liver and kidney function and complete blood cell count
timeFrame: baseline, 12 months, 24 months
measure: Changes in diet from baseline
timeFrame: Baseline, 12 months, 24 months
measure: Changes in physical activity from baseline
timeFrame: Baseline, 12 months, 24 months
measure: Changes from baseline in adverse events
timeFrame: Baseline, 12 months, 24 months
Other outcomes:
Locations:
city: Regina
country: Canada
facility: University of Regina
state: Saskatchewan
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Philip D Chilibeck, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Regina
name: Darren Candow, PhD
role: PRINCIPAL_INVESTIGATOR
References: