Randomized Control Trial of Bone Loading Exercises Versus Risedronate on Bone Health in Post-Menopausal Women
| Registry | NCT02186600, acronym HOPS |
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| Status | Completed |
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| Phase | Phase 3 |
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| Study type | Interventional; randomized, parallel, masking: none, treatment |
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| Enrollment | 276 (Actual) |
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| Sponsor | University of Nebraska (Other); collaborators: Creighton University Medical Center |
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| Conditions | Osteopenia |
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| Interventions | Calcium Carbonate, Vitamin D3, Risedronate, Bone-loading exercises (Drug, behavioral) |
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| Dates | start 2015-02-01, primary completion 2019-06-01, completion 2019-06-01, first posted 2014-07-10, last updated 2023-10-05 |
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| Locations | 1 site in United States |
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Related Papers Related Patents Related Grants Related Experts
All trials for Osteopenia All trials of Calcium Carbonate All trials of Vitamin D3
-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.
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+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.
+Arms and interventions
| Arm | Type | Interventions | Description |
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| Control | Active comparator | Drug: Calcium Carbonate; Drug: Vitamin D3 | 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. |
| Risedronate | Experimental | Drug: Calcium Carbonate; Drug: Vitamin D3; Drug: 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. |
| Exercise | Experimental | Drug: Calcium Carbonate; Drug: Vitamin D3; Behavioral: Bone-loading exercises | 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 (Drug), also known as generic: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
- Vitamin D3 (Drug), also known as generic: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.
- Risedronate (Drug), also known as Actonel: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.
- Bone-loading exercises (Behavioral): Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.
+Outcome measures
Primary outcomes
- 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 outcomes
- 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.
+Eligibility
Sex: Female, ages: 19 Years to any
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.
+Posted results
Participant flow
| Milestone | Control | Risedronate | Exercise |
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| Started | 93 | 91 | 92 |
| Completed | 77 | 78 | 72 |
| Not completed | 16 | 13 | 20 |
Outcome results
- Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. (Primary), Mean, mg^2/mm^4: Control 2098.7 +/- 334.7; Risedronate 1993.3 +/- 292.3; Exercise 2001 +/- 332.1 (p 0.7)
- Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. (Secondary), Mean, g/cm^2: Control 0.889 +/- 0.076; Risedronate 0.892 +/- 0.06; Exercise 0.886 +/- 0.064 (p 0.01)
- Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. (Secondary), Mean, nanoMolar Bone Collagen Equivalents/L: Control 13.99 +/- 4.22; Risedronate 14.31 +/- 4.44; Exercise 15.03 +/- 5.45 (p <0.007)
Adverse events
Time frame: 12 months for each participant
| Arm | Deaths | Serious adverse events | Other adverse events |
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| Control | 0/93 (0.0%) | 0/93 (0.0%) | 9/93 (9.7%) |
| Risedronate | 0/91 (0.0%) | 0/91 (0.0%) | 30/91 (33.0%) |
| Exercise | 0/92 (0.0%) | 0/92 (0.0%) | 4/92 (4.3%) |
Other adverse events by term
| Term | Organ system | Control | Risedronate | Exercise |
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| Constipation | Gastrointestinal disorders | 9/93 | 13/91 | 2/92 |
| Gi disturbances | Gastrointestinal disorders | 0/93 | 4/91 | 0/92 |
| muscle or joint pain | Musculoskeletal and connective tissue disorders | 0/93 | 11/91 | 2/92 |
| Chest Pain or Dizziness | Cardiac disorders | 0/93 | 2/91 | 0/92 |
+Locations (1)
| Facility | City | Country | Status |
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| University of Nebraska Medical Center | Omaha, Nebraska | United States | |
+Publications
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- Going S, Lohman T, Houtkooper L, Metcalfe L, Flint-Wagner H, Blew R, Stanford V, Cussler E, Martin J, Teixeira P, Harris M, Milliken L, Figueroa-Galvez A, Weber J. Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Osteoporos Int. 2003 Aug;14(8):637-43. doi: 10.1007/s00198-003-1436-x. Epub 2003 Jul 3. PMID 12844212
- Kemmler W, Engelke K, Lauber D, Weineck J, Hensen J, Kalender WA. Exercise effects on fitness and bone mineral density in early postmenopausal women: 1-year EFOPS results. Med Sci Sports Exerc. 2002 Dec;34(12):2115-23. doi: 10.1097/00005768-200212000-00038. PMID 12471325
- Vainionpaa A, Korpelainen R, Vaananen HK, Haapalahti J, Jamsa T, Leppaluoto J. Effect of impact exercise on bone metabolism. Osteoporos Int. 2009 Oct;20(10):1725-33. doi: 10.1007/s00198-009-0881-6. Epub 2009 Mar 5. PMID 19262975
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- Prentice RL, Pettinger MB, Jackson RD, Wactawski-Wende J, Lacroix AZ, Anderson GL, Chlebowski RT, Manson JE, Van Horn L, Vitolins MZ, Datta M, LeBlanc ES, Cauley JA, Rossouw JE. Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study. Osteoporos Int. 2013 Feb;24(2):567-80. doi: 10.1007/s00198-012-2224-2. Epub 2012 Dec 4. PMID 23208074
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- Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64. doi: 10.1001/jama.293.18.2257. PMID 15886381
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- Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD. Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone. 2004 Apr;34(4):736-46. doi: 10.1016/j.bone.2003.12.013. PMID 15050906
- Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Dawson-Hughes B, El-Hajj Fuleihan G, Johansson H, Leslie WD, Lewiecki EM, Luckey M, Oden A, Papapoulos SE, Poiana C, Rizzoli R, Wahl DA, McCloskey EV; Task Force of the FRAX Initiative. Interpretation and use of FRAX in clinical practice. Osteoporos Int. 2011 Sep;22(9):2395-411. doi: 10.1007/s00198-011-1713-z. Epub 2011 Jul 21. PMID 21779818
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- Results publication: Waltman N, Kupzyk KA, Flores LE, Mack LR, Lappe JM, Bilek LD. Bone-loading exercises versus risedronate for the prevention of osteoporosis in postmenopausal women with low bone mass: a randomized controlled trial. Osteoporos Int. 2022 Feb;33(2):475-486. doi: 10.1007/s00198-021-06083-2. Epub 2021 Sep 14. PMID 34519832
- Results publication: Bilek LD, Waltman NL, Lappe JM, Kupzyk KA, Mack LR, Cullen DM, Berg K, Langel M, Meisinger M, Portelli-Trinidad A, Lang M. Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women. BMC Womens Health. 2016 Aug 30;16(1):59. doi: 10.1186/s12905-016-0339-x. PMID 27576310
+Study documents
+Investigators