Osteopenia
Conditions
Keywords
Low bone mass, Post-menopausal women, Bone mineral density, Bone structure, Bone turnover, Bone-loading exercises, calcium and vitamin D, risedronate
Brief summary
The purpose of this study is to identify the best way to prevent bone loss in the first years after menopause. The HOPS study will compare bone loss at 12 months in women: 1) who take calcium and vitamin D only; 2) who take calcium and vitamin D plus the medication risedronate; or 3) who take calcium and vitamin D plus participate in bone-loading exercises. Our central hypothesis is that improvements in bone health will be greater in women randomized to bone-loading exercises with calcium and vitamin D compared to women who take calcium and vitamin D only or women who take calcium and vitamin D plus risedronate.
Detailed description
This randomized controlled trial (RCT) will compare changes after 12 months in bone structure, bone mineral density (BMD), and bone turnover in women with low bone mass who are within 5 years of menopause. Women will be randomized to one control and 2 treatment groups (n =103 per group): 1) calcium + vitamin D (CaD) alone (Control); 2) Bisphosphonate (BP) plus optimal CaD (Risedronate); and 3) a bone loading exercise program plus optimal CaD (Exercise). Our central hypothesis is that improvements in bone health will be greater in subjects randomized to the exercise group compared to subjects in either the control or risedronate groups. Specific Aims: Aims 1, 2, and 3 are to compare control, risedronate, and exercise group subjects on changes in bone structure at the tibia and hip (measured by pQCT and Hip Structural Analysis) (Aim 1) ; on changes in BMD at the total hip, femoral neck, and spine (Aim 2); and on changes in serum markers of bone formation and resorption (Aim 3). In addition, Aim 4 will explore relationships between adherence to exercise (% sessions attended) or adherence to risedronate (% pills taken) and changes in bone structure.
Interventions
DRUGCalcium Carbonate
Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
DRUGVitamin D3
Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.
DRUGRisedronate
Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.
BEHAVIORALBone-loading exercises
Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.
Sponsors
Creighton University Medical Center
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized to 3 treatment groups: Calcium + vitamin D only; risedronate and calcium + vitamin D; bone building exercises and calcium + vitamin D
Eligibility
Sex/Gender
FEMALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women who are in their first 5 years of menopause * Have a T score between -1 and -2.49 at the femoral neck, total hip, or L1-L4 spine * Be 19 years of age or older * Have their health care provider's permission to enroll in the study.
Exclusion criteria
* Have osteoporosis * Have a 10 yr probability of hip fracture \>3% or major fracture \>20% based on results of the fracture risk assessment (FRAX) tool * Currently take bisphosphonates, estrogen replacement therapy, glucocorticosteroids, or other drugs affecting bone * Currently participate in a resistance training or high impact weight bearing exercise program three or more times weekly * Weigh \>300 lbs * Have abnormal results for the following laboratory tests: serum 25(OH)D; serum creatinine; serum calcium; parathyroid hormone (PTH); thyroid stimulating hormone (TSH). * Have Paget's disease, heart disease, uncontrolled hypertension, renal disease, or other concomitant conditions that prohibit participation in exercises, risedronate therapy, or use of CaD supplements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline, 6, and 12 months | Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group. BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline,6, and 12 months | Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA). |
| Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline, 6, 12 months | Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (\ 5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have \
1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml. | 93 |
| Risedronate Subjects in the risedronate group will take 35 mg of the bisphosphonate risedronate weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group. | 91 |
| Exercise Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs. | 92 |
| Total | 276 |
Baseline characteristics
| Characteristic | Control | Risedronate | Exercise | Total |
|---|---|---|---|---|
| Age, Continuous | 54.34 years STANDARD_DEVIATION 3.3 | 54.53 years STANDARD_DEVIATION 3.07 | 54.47 years STANDARD_DEVIATION 3.11 | 54.4 years STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 12 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 80 Participants | 80 Participants | 245 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Family History of Low Bone Mass or Osteoporosis | 57 Participants | 52 Participants | 53 Participants | 162 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 89 Participants | 84 Participants | 88 Participants | 261 Participants |
| Sex: Female, Male Female | 93 Participants | 91 Participants | 92 Participants | 276 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 91 | 0 / 92 |
| other Total, other adverse events | 9 / 93 | 30 / 91 | 4 / 92 |
| serious Total, serious adverse events | 0 / 93 | 0 / 91 | 0 / 92 |
Outcome results
Primary
Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.
Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group. BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT).
Time frame: Baseline, 6, and 12 months
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 2105.89 mg^2/mm^4 | Standard Deviation 322.822 |
| Control | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 2098.7 mg^2/mm^4 | Standard Deviation 334.7 |
| Control | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 2107.2 mg^2/mm^4 | Standard Deviation 326.4 |
| Risedronate | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 1997.32 mg^2/mm^4 | Standard Deviation 307.103 |
| Risedronate | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 1993.3 mg^2/mm^4 | Standard Deviation 292.3 |
| Risedronate | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 2014.2 mg^2/mm^4 | Standard Deviation 306.7 |
| Exercise | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 2001 mg^2/mm^4 | Standard Deviation 332.1 |
| Exercise | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 2009.2 mg^2/mm^4 | Standard Deviation 280.4 |
| Exercise | Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 1987.42 mg^2/mm^4 | Standard Deviation 300.136 |
p-value: 0.7hierarchical linear modeling
Secondary
Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.
Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA).
Time frame: Baseline,6, and 12 months
Population: Intent to treat analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 0.885 g/cm^2 | Standard Deviation 0.07 |
| Control | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | .887 g/cm^2 | Standard Deviation 0.0755 |
| Control | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 0.889 g/cm^2 | Standard Deviation 0.076 |
| Risedronate | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 0.911 g/cm^2 | Standard Deviation 0.07 |
| Risedronate | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 0.892 g/cm^2 | Standard Deviation 0.06 |
| Risedronate | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | .907 g/cm^2 | Standard Deviation 0.0666 |
| Exercise | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | .878 g/cm^2 | Standard Deviation 0.0619 |
| Exercise | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 0.886 g/cm^2 | Standard Deviation 0.064 |
| Exercise | Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 0.885 g/cm^2 | Standard Deviation 0.065 |
p-value: 0.01hierarchical linear modeling
Secondary
Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.
Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (\ 5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx.
Time frame: Baseline, 6, 12 months
Population: Intention to treat for persons who had valid data at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 12.16 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 3.84 |
| Control | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 13.99 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 4.22 |
| Control | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 12.36 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 3.48 |
| Risedronate | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 10.30 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 3.93 |
| Risedronate | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 14.31 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 4.44 |
| Risedronate | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 11.42 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 4.71 |
| Exercise | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | Baseline | 15.03 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 5.45 |
| Exercise | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 12 Months | 13.92 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 5.84 |
| Exercise | Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | 6 Months | 13.36 nanoMolar Bone Collagen Equivalents/L | Standard Deviation 5.83 |
p-value: <0.007hierarchical linear modeling