Clinical trial NCT02186600: Heartland Osteoporosis Prevention Study
Official title: Randomized Control Trial of Bone Loading Exercises Versus Risedronate on Bone Health in Post-Menopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteopenia
Keywords: Low bone mass
Post-menopausal women
Bone mineral density
Bone structure
Bone turnover
Bone-loading exercises
calcium and vitamin D
risedronate
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Creighton University Medical Center
First posted: 2014-07-10
Enrollment: 276
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized to 3 treatment groups: Calcium + vitamin D only; risedronate and calcium + vitamin D; bone building exercises and calcium + vitamin D
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.
timeFrame: Baseline, 6, and 12 months
Secondary outcomes:
measure: Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.
timeFrame: Baseline,6, and 12 months
measure: Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.
timeFrame: Baseline, 6, 12 months
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Nancy L Waltman, PhD, APRN-NP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nebraska
name: Laura Bilek, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bocalini DS, Serra AJ, dos Santos L, Murad N, Levy RF. Strength training preserves the bone mineral density of postmenopausal women without hormone replacement therapy. J Aging Health. 2009 Jun;21(3):519-27. doi: 10.1177/0898264309332839. Epub 2009 Feb 27.
citation: Uusi-Rasi K, Kannus P, Cheng S, Sievanen H, Pasanen M, Heinonen A, Nenonen A, Halleen J, Fuerst T, Genant H, Vuori I. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone. 2003 Jul;33(1):132-43. doi: 10.1016/s8756-3282(03)00082-6.
citation: Bergstrom I, Landgren B, Brinck J, Freyschuss B. Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density. Osteoporos Int. 2008 Feb;19(2):177-83. doi: 10.1007/s00198-007-0445-6. Epub 2007 Sep 1.
citation: Dane C, Dane B, Cetin A, Erginbas M. Effect of risedronate on biochemical marker of bone resorption in postmenopausal women with osteoporosis or osteopenia. Gynecol Endocrinol. 2008 Apr;24(4):207-13. doi: 10.1080/09513590801895617.
citation: Cussler EC, Going SB, Houtkooper LB, Stanford VA, Blew RM, Flint-Wagner HG, Metcalfe LL, Choi JE, Lohman TG. Exercise frequency and calcium intake predict 4-year bone changes in postmenopausal women. Osteoporos Int. 2005 Dec;16(12):2129-41. doi: 10.1007/s00198-005-2014-1. Epub 2005 Nov 10.
citation: Elders PJ, Netelenbos JC, Lips P, van Ginkel FC, Khoe E, Leeuwenkamp OR, Hackeng WH, van der Stelt PF. Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. J Clin Endocrinol Metab. 1991 Sep;73(3):533-40. doi: 10.1210/jcem-73-3-533.
citation: Valimaki MJ, Farrerons-Minguella J, Halse J, Kroger H, Maroni M, Mulder H, Munoz-Torres M, Saaf M, Snorre Ofjord E. Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers in late-postmenopausal women with osteopenia: a multinational, 24-month, randomized, double-blind, placebo-controlled, parallel-group, phase III trial. Clin Ther. 2007 Sep;29(9):1937-49. doi: 10.1016/j.clinthera.2007.09.017.
citation: Vainionpaa A, Korpelainen R, Sievanen H, Vihriala E, Leppaluoto J, Jamsa T. Effect of impact exercise and its intensity on bone geometry at weight-bearing tibia and femur. Bone. 2007 Mar;40(3):604-11. doi: 10.1016/j.bone.2006.10.005. Epub 2006 Nov 30.
citation: Waltman NL, Twiss JJ, Ott CD, Gross GJ, Lindsey AM, Moore TE, Berg K, Kupzyk K. The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial. Osteoporos Int. 2010 Aug;21(8):1361-9. doi: 10.1007/s00198-009-1083-y. Epub 2009 Oct 3.
citation: Fogelman I, Ribot C, Smith R, Ethgen D, Sod E, Reginster JY. Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group. J Clin Endocrinol Metab. 2000 May;85(5):1895-900. doi: 10.1210/jcem.85.5.6603.
citation: 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.
citation: 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.
citation: 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.
citation: Klentrou P, Slack J, Roy B, Ladouceur M. Effects of exercise training with weighted vests on bone turnover and isokinetic strength in postmenopausal women. J Aging Phys Act. 2007 Jul;15(3):287-99. doi: 10.1123/japa.15.3.287.
citation: 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.
citation: Somford MP, Geurts GF, den Teuling JW, Thomassen BJ, Draijer WF. Long-Term Alendronate Use Not without Consequences? Int J Rheumatol. 2009;2009:253432. doi: 10.1155/2009/253432. Epub 2010 Jan 27.
citation: Whyte MP. Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res. 2009 Jun;24(6):1132-4. doi: 10.1359/jbmr.081253.
citation: Caulfield MP, Reitz RE. Biochemical markers of bone turnover and their utility in osteoporosis. MLO Med Lab Obs. 2004 Apr;36(4):34-7. No abstract available.
citation: Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. doi: 10.1093/ajcn/84.1.18.
citation: 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.
citation: Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab. 2005 Mar;90(3):1897-9. doi: 10.1210/jc.2005-0057. No abstract available.
citation: Schneider JP. Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics. 2006 Jan;61(1):31-3. No abstract available.
citation: Hamdy RC, Petak SM, Lenchik L; International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. Which central dual X-ray absorptiometry skeletal sites and regions of interest should be used to determine the diagnosis of osteoporosis? J Clin Densitom. 2002;5 Suppl:S11-8. doi: 10.1385/jcd:5:3s:s11.
citation: van der Linden JC, Weinans H. Effects of microarchitecture on bone strength. Curr Osteoporos Rep. 2007 Jun;5(2):56-61. doi: 10.1007/s11914-007-0003-3.
citation: Akhter MP, Lappe JM, Davies KM, Recker RR. Transmenopausal changes in the trabecular bone structure. Bone. 2007 Jul;41(1):111-6. doi: 10.1016/j.bone.2007.03.019. Epub 2007 Apr 10.
citation: Beck TJ. Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep. 2007 Jun;5(2):49-55. doi: 10.1007/s11914-007-0002-4.
citation: Twiss JJ, Waltman NL, Berg K, Ott CD, Gross GJ, Lindsey AM. An exercise intervention for breast cancer survivors with bone loss. J Nurs Scholarsh. 2009 Mar;41(1):20-7. doi: 10.1111/j.1547-5069.2009.01247.x.
citation: Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause. 2010 Jan-Feb;17(1):25-54; quiz 55-6. doi: 10.1097/gme.0b013e3181c617e6.
citation: Lappe JM, Davies KM, Travers-Gustafson D, Heaney RP. Vitamin D status in a rural postmenopausal female population. J Am Coll Nutr. 2006 Oct;25(5):395-402. doi: 10.1080/07315724.2006.10719551.
citation: 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.
citation: 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.
citation: Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, Nieman DC, Swain DP; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011 Jul;43(7):1334-59. doi: 10.1249/MSS.0b013e318213fefb.
citation: Maddalozzo GF, Widrick JJ, Cardinal BJ, Winters-Stone KM, Hoffman MA, Snow CM. The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women. Bone. 2007 May;40(5):1244-51. doi: 10.1016/j.bone.2006.12.059. Epub 2006 Dec 29.
citation: Ashe MC, Gorman E, Khan KM, Brasher PM, Cooper DM, McKay HA, Liu-Ambrose T. Does frequency of resistance training affect tibial cortical bone density in older women? A randomized controlled trial. Osteoporos Int. 2013 Feb;24(2):623-32. doi: 10.1007/s00198-012-2000-3. Epub 2012 May 12.
citation: 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.
citation: 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.