Bone Resorption, Osteoporosis
Conditions
Keywords
Dietary protein, Calcium, Parathyroid hormone, Bone markers, Bone mineral density, IGF-1, Urine Calcium
Brief summary
Women and men consuming a low protein diet may be at risk for bone loss. The purpose of this study is to determine whether a daily protein supplement will improve bone health among healthy older adults.
Detailed description
Dietary protein plays an important role in maintaining balanced calcium levels in the body. Protein's impact on skeletal health remains unclear. It is well accepted that increasing dietary protein results in greater excretion of calcium through urine. The excreted calcium is thought to come in part from bone, which would suggest a negative effect on bone health. However, recent studies have found that higher protein intake is, in fact, associated with higher bone mineral density and lower rates of bone loss. The purpose of this study is to determine if a daily protein supplement will improve bone health and hormonal measures of bone metabolism among healthy older men and women who consume low-to-normal levels of dietary protein. This study will last 18 months. For the duration of the study, participants will be randomly assigned to receive either a 40-gram protein supplement or placebo daily. There will be a total of nine study visits that will occur at screening, study entry, Month 1.5, and every three months thereafter. Dietary records, nutritional counseling, glucose finger stick tests, and questionnaires related to falls, physical activity, habits, and study satisfaction will occur at all study visits. Blood and urine collection, functional testing, and bone mineral density (BMD) testing will occur at selected visits. At Months 0 and 18, half of the participants will undergo a quantitative computed tomography (CT) scan to determine bone mineral density.
Interventions
DIETARY_SUPPLEMENTWhey protein supplement
40-g whey protein supplement daily for 18 months
DIETARY_SUPPLEMENTPlacebo
Placebo supplement daily for 18 months
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Office of Dietary Supplements (ODS)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Willing to travel to one of the study sites * Women age 60 years or greater, men age 70 years or greater * Dietary protein intake level between 0.6 g/kg and 1.0 g/kg at baseline
Exclusion criteria
* Active Paget's disease * Primary hyperparathyroidism or unexplained hypercalcemia * Untreated hyperthyroidism or hyperthyroidism that has resulted from medical treatment * Diabetes mellitus type 1 * Cancer diagnosis for solid malignancies (e.g., cancer of the colon, breast,prostate, lungs, lymphocytes) within the 18 months prior to study entry * Long-term use of chemotherapeutic drugs, aromatase inhibitors, or tamoxifen * Active treatment for leukemia or multiple myeloma * Active inflammatory bowel disease * Life expectancy of less than 2 years * Current and ongoing use of methotrexate, phenytoin, phenobarbital, or inhaled corticosteroids at a dose of greater than 800 mcg/day * Use of raloxifene, estrogen, androgen, progesterone, soy isoflavones, oral glucocorticoids, or herbal supplements with estrogenic activity OR a change in dosage of thyroid medications within the 1 year prior to study entry if unwilling to avoid such agents during the duration of the study * Current use of antiresorptive agents (e.g., calcitonin or bisphosphonates). More information about this criterion can be found in the protocol. * serum creatinine greater than 1.2 mg/dl * History of chronic liver disease or evidence of liver disease at screening * Bilateral hip replacement * women who have a bone mineral density T-score \< -2.5 at either the hip or spine unless they have decided to decline treatment with conventional anti-osteoporotic medications * Body mass index (BMI) greater than 32 or less than 19 * Use of proton-pump inhibitors taken twice daily * Fasting glucose level greater than 110 mg/dl * Serum albumin level less than 3.0 mg/dl * Kidney stones or history of kidney stones within the 3 years prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anterior-posterior Spine Bone Mass Density Measured by Dual Energy X-ray Absorptiometry (DXA) Compared to Baseline | Measured at baseline and 18 months | There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass. |
| Change in Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) Compared to Baseline | Measured at baseline and 18 months | There is no normative data for quantitative computed tomography it is based on local experience. |
| Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at Baseline | Measured at 0 months | There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass. |
| Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 9 Months | Measured at 9 months | There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass. |
| Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 18 Months | Measured at 18 months | There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass. |
| Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at Baseline | Measured at 0 months | There is no normative data for quantitative computed tomography it is based on local experience. |
| Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at 18 Months | Measured at 18 months | There is no normative data for quantitative computed tomography it is based on local experience. |
Countries
United States
Participant flow
Recruitment details
Recruitment started in June 2007 and the last participant was screened in October 2010. Subjects were recruited to the Yale Center for Clinical Investigation in New Haven, CT or the University of Connecticut Health Center in Farmington, CT.
Pre-assignment details
Subjects were randomized 1 month after screening if they were found eligible after screening. Between screening and randomization their calcium and vitamin D intake was stabilized for baseline measurements.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months Participants will receive a placebo supplement daily (40 g maltodextrin).
Placebo : Placebo supplement daily for 18 months | 102 |
| Protein Powder 40 g Daily for 18 Months Participants will receive a protein supplement daily (40 g whey protein supplement).
Whey protein supplement : 40-g whey protein supplement daily for 18 months | 106 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discountinued from treatment/ f/u cont. | 12 | 25 |
| Overall Study | Lost to Follow-up | 30 | 20 |
Baseline characteristics
| Characteristic | Placebo Carbohydrate 40 g Daily for 18 Months | Protein Powder 40 g Daily for 18 Months | Total |
|---|---|---|---|
| Age, Continuous | 70.5 years STANDARD_DEVIATION 6.4 | 69.9 years STANDARD_DEVIATION 6.1 | 70.2 years STANDARD_DEVIATION 6.2 |
| Region of Enrollment United States | 102 participants | 106 participants | 208 participants |
| Sex: Female, Male Female | 89 Participants | 89 Participants | 178 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 102 | 56 / 106 |
| serious Total, serious adverse events | 14 / 102 | 4 / 106 |
Outcome results
Primary
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 18 Months
There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass.
Time frame: Measured at 18 months
Population: All participants were analyzed using the mixed models method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 18 Months | 1.14 g/cm^2 | Standard Error 0.02 |
| Protein Powder 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 18 Months | 1.12 g/cm^2 | Standard Error 0.01 |
Primary
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 9 Months
There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass.
Time frame: Measured at 9 months
Population: All participants were analyzed using the mixed models method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 9 Months | 1.14 g/cm^2 | Standard Error 0.02 |
| Protein Powder 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 9 Months | 1.12 g/cm^2 | Standard Error 0.01 |
Primary
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at Baseline
There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass.
Time frame: Measured at 0 months
Population: All participants were analyzed using the mixed models method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at Baseline | 1.10 g/cm^2 | Standard Error 0.01 |
| Protein Powder 40 g Daily for 18 Months | Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at Baseline | 1.13 g/cm^2 | Standard Error 0.01 |
Primary
Change in Anterior-posterior Spine Bone Mass Density Measured by Dual Energy X-ray Absorptiometry (DXA) Compared to Baseline
There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass.
Time frame: Measured at baseline and 18 months
Population: Only participants with data at the baseline and 18 month timeframe were used in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Change in Anterior-posterior Spine Bone Mass Density Measured by Dual Energy X-ray Absorptiometry (DXA) Compared to Baseline | 0.51 percentage change | Standard Error 0.38 |
| Protein Powder 40 g Daily for 18 Months | Change in Anterior-posterior Spine Bone Mass Density Measured by Dual Energy X-ray Absorptiometry (DXA) Compared to Baseline | 0.51 percentage change | Standard Error 0.38 |
Primary
Change in Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) Compared to Baseline
There is no normative data for quantitative computed tomography it is based on local experience.
Time frame: Measured at baseline and 18 months
Population: Only participants with data at the baseline and 18 month timeframe were used in the analysis. Only half of the study partipants were randomized to receive Quantitative Computed Tomography testing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Change in Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) Compared to Baseline | -0.07 percent change | Standard Error 1.08 |
| Protein Powder 40 g Daily for 18 Months | Change in Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) Compared to Baseline | -2.64 percent change | Standard Error 1.81 |
Primary
Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at 18 Months
There is no normative data for quantitative computed tomography it is based on local experience.
Time frame: Measured at 18 months
Population: All participants were analyzed using the mixed models method. For the Quantitative Computed Tomography (QCT) test only half of the participants were randomized to receive it.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at 18 Months | 106 mg/cm^3 | Standard Error 4.07 |
| Protein Powder 40 g Daily for 18 Months | Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at 18 Months | 99.3 mg/cm^3 | Standard Error 4.29 |
Primary
Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at Baseline
There is no normative data for quantitative computed tomography it is based on local experience.
Time frame: Measured at 0 months
Population: All participants were analyzed using the mixed models method. For the Quantitative Computed Tomography (QCT) test only half of the participants were randomized to receive it.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Carbohydrate 40 g Daily for 18 Months | Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at Baseline | 106 mg/cm^3 | Standard Error 3.72 |
| Protein Powder 40 g Daily for 18 Months | Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at Baseline | 103 mg/cm^3 | Standard Error 4.51 |