Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative

BMC Geriatrics

Sylvia Wassertheil-Smoller⁷  Robert B Wallace⁴  Moritz Wyler von Ballmoos²  Judith K Ockene³  Ryan M Carnahan⁴  Jean Wactawski-Wende¹  Jennifer W Bea⁵  Mary Pettinger⁸  Bernhard Haring⁶ 

[1] Department of Social and Preventive Medicine, University at Buffalo, SUNY School of Public Health and Health Professions, Buffalo, NY, USA;Department of Surgery & Division of Cardiothoracic Surgery, Froedtert Memorial Hospital & Medical College of Wisconsin, Milwaukee, WI, USA;Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA;Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA;Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;Department of Internal Medicine I, Comprehensive Heart Failure Center, University of Würzburg, Oberdürrbacher Strasse 6, Würzburg, 97080, Germany;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA;Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

关键词: Aging;    Bone mineral density;    Fractures;    Falls;    Laxative use;   

Others  :  857744
DOI  :  10.1186/1471-2318-13-38

 received in 2012-08-14, accepted in 2013-04-22,  发布年份 2013

【 摘 要 】

Background

Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated.

Methods

This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (≥2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI.

Results

Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake.

Conclusion

These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use.

【 授权许可】

   
2013 Haring et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Consumer Health Care Association: OTC Sales by Category. 2011. [http://www.chpa-info.org/pressroom/Sales_Category.aspx webcite] (Last accessed 03-25-2013
• [2]Baker EH, Sandle GI: Complications of laxative abuse. Annu Rev Med 1996, 47:127-134.
• [3]Moriarty KJ, Silk DB: Laxative abuse. Dig Dis 1988, 6(1):15-29.
• [4]Roerig JL, Steffen KJ, Mitchell JE, Zunker C: Laxative abuse: epidemiology, diagnosis and management. Drugs 2010, 70(12):1487-1503.
• [5]Fleischer N, Brown H, Graham DY, Delena S: Chronic laxative-induced hyperaldosteronism and hypokalemia simulating Bartter's syndrome. Ann Intern Med 1969, 70(4):791-798.
• [6]Sankar NS, Donaldson D: Lessons to be learned: a case study approach diuretic therapy and a laxative causing electrolyte and water imbalance, loss of attention, a fall and subsequent fractures of the tibia and fibula in an elderly lady. J R Soc Promot Health 1998, 118(4):237-240.
• [7]Yakabowich M: Prescribe with care. The role of laxatives in the treatment of constipation. J Gerontol Nurs 1990, 16(7):4-11.
• [8]Decaux G: Is asymptomatic hyponatremia really asymptomatic? Am J Med 2006, 119(7 Suppl 1):S79-82.
• [9]Gankam Kengne F, Andres C, Sattar L, Melot C, Decaux G: Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM 2008, 101(7):583-588.
• [10]Kinsella S, Moran S, Sullivan MO, Molloy MG, Eustace JA: Hyponatremia independent of osteoporosis is associated with fracture occurrence. Clin J Am Soc Nephrol 2010, 5(2):275-280.
• [11]Sajadieh A, Binici Z, Mouridsen MR, Nielsen OW, Hansen JF, Haugaard SB: Mild hyponatremia carries a poor prognosis in community subjects. Am J Med 2009, 122(7):679-686.
• [12]Cranney A, Weiler HA, O'Donnell S, Puil L: Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr 2008, 88(2):513S-519S.
• [13]Janssen HC, Samson MM, Verhaar HJ: Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 2002, 75(4):611-615.
• [14]McCarroll KG, Robinson DJ, Coughlan A, Healy M, Kenny RA, Cunningham C: Vitamin D and orthostatic hypotension. Age Ageing 2012, 41(6):810-813.
• [15]Carbone LD, Johnson KC, Bush AJ, Robbins J, Larson JC, Thomas A, LaCroix AZ: Loop diuretic use and fracture in postmenopausal women: findings from the Women's Health Initiative. Arch Intern Med 2009, 169(2):132-140.
• [16]Carbone LD, Johnson KC, Robbins J, Larson JC, Curb JD, Watson K, Gass M, Lacroix AZ: Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: findings from the women's health initiative (WHI). J Bone Miner Res 2010, 25(4):873-881.
• [17]Hix JK, Silver S, Sterns RH: Diuretic-associated hyponatremia. Semin Nephrol 2011, 31(6):553-566.
• [18]Rastogi D, Pelter MA, Deamer RL: Evaluations of hospitalizations associated with thiazide-associated hyponatremia. J Clin Hypertens (Greenwich) 2012, 14(3):158-164.
• [19]Sonnenblick M, Friedlander Y, Rosin AJ: Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. Chest 1993, 103(2):601-606.
• [20]Kallin K, Gustafson Y, Sandman PO, Karlsson S: Drugs and falls in older people in geriatric care settings. Aging Clin Exp Res 2004, 16(4):270-276.
• [21]Kallin K, Gustafson Y, Sandman PO, Karlsson S: Factors associated with falls among older, cognitively impaired people in geriatric care settings: a population-based study. Am J Geriatr Psychiatry 2005, 13(6):501-509.
• [22]Lundin-Olsson L, Jensen J, Nyberg L, Gustafson Y: Predicting falls in residential care by a risk assessment tool, staff judgement, and history of falls. Aging Clin Exp Res 2003, 15(1):51-59.
• [23]Luukinen H, Koski K, Laippala P, Kivela SL: Predictors for recurrent falls among the home-dwelling elderly. Scand J Prim Health Care 1995, 13(4):294-299.
• [24]Luukinen H, Koski K, Laippala P, Kivela SL: Risk factors for recurrent falls in the elderly in long-term institutional care. Public Health 1995, 109(1):57-65.
• [25]Ryynanen OP, Kivela SL, Honkanen R, Laippala P, Saano V: Medications and chronic diseases as risk factors for falling injuries in the elderly. Scand J Soc Med 1993, 21(4):264-271.
• [26]Spector W, Shaffer T, Potter DE, Correa-de-Araujo R, Rhona Limcangco M: Risk factors associated with the occurrence of fractures in U.S. nursing homes: resident and facility characteristics and prescription medications. J Am Geriatr Soc 2007, 55(3):327-333.
• [27]Svensson ML, Rundgren A, Landahl S: Falls in 84- to 85-year-old people living at home. Accid Anal Prev 1992, 24(5):527-537.
• [28]Bloch F, Thibaud M, Dugue B, Breque C, Rigaud AS, Kemoun G: Laxatives as a risk factor for iatrogenic falls in elderly subjects: myth or reality? Drugs Aging 2010, 27(11):895-901.
• [29]von Heideken WP, Gustafson Y, Kallin K, Jensen J, Lundin-Olsson L: Falls in very old people: the population-based Umea 85+ study in Sweden. Arch Gerontol Geriatr 2009, 49(3):390-396.
• [30]McPherson E, Dunsmuir RA: Hyponatraemia in hip fracture patients. Scott Med J 2002, 47(5):115-116.
• [31]Ayus JC, Moritz ML: Bone disease as a new complication of hyponatremia: moving beyond brain injury. Clin J Am Soc Nephrol 2010, 5(2):167-168.
• [32]Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB: Effect of Vitamin D on falls: a meta-analysis. JAMA 2004, 291(16):1999-2006.
• [33]Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY: Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 2006, 78(5):257-270.
• [34]Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP: A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc 2007, 55(2):234-239.
• [35]Gennari C: Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutr 2001, 4(2B):547-559.
• [36]Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S: Reducing fracture risk with calcium and vitamin D. Clin Endocrinol (Oxf) 2010, 73(3):277-285.
• [37]Malabanan AO, Holick MF: Vitamin D and bone health in postmenopausal women. J Womens Health (Larchmt) 2003, 12(2):151-156.
• [38]Rodriguez-Martinez MA, Garcia-Cohen EC: Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis. Pharmacol Ther 2002, 93(1):37-49.
• [39]Edwards MH, Jameson K, Denison H, Harvey NC, Sayer AA, Dennison EM, Cooper C: Clinical risk factors, bone density and fall history in the prediction of incident fracture among men and women. Bone 2013, 52(2):541-547.
• [40]Pryor T, Wiederman MW, McGilley B: Laxative abuse among women with eating disorders: an indication of psychopathology? Int J Eat Disord 1996, 20(1):13-18.
• [41]Vanin JR, Saylor KE: Laxative abuse: a hazardous habit for weight control. J Am Coll Health 1989, 37(5):227-230.
• [42]Campbell AJ, Busby WJ, Horwath CC: Factors associated with constipation in a community based sample of people aged 70 years and over. J Epidemiol Community Health 1993, 47(1):23-26.
• [43]Everhart JE, Go VL, Johannes RS, Fitzsimmons SC, Roth HP, White LR: A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989, 34(8):1153-1162.
• [44]Koch T, Hudson S: Older people and laxative use: literature review and pilot study report. J Clin Nurs 2000, 9(4):516-525.
• [45]McCrea GL, Miaskowski C, Stotts NA, Macera L, Paul SM, Varma MG: Gender differences in self-reported constipation characteristics, symptoms, and bowel and dietary habits among patients attending a specialty clinic for constipation. Gend Med 2009, 6(1):259-271.
• [46]Design of the Women's Health Initiative clinical trial and observational study: The Women's Health Initiative Study Group. Control Clin Trials 1998, 19(1):61-109.
• [47]Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006, 354(7):669-683.
• [48]Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M: The Women's Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol 2003, 13(9 Suppl):S107-121.
• [49]Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM: Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006, 295(6):629-642.
• [50]Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002, 288(3):321-333.
• [51]Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE: The Women's Health Initiative recruitment methods and results. Ann Epidemiol 2003, 13(9 Suppl):S18-77.
• [52]Masud T, Morris RO: Epidemiology of falls. Age Ageing 2001, 30(Suppl 4):3-7.
• [53]Stalenhoef PA, Diederiks JP, Knottnerus JA, Kester AD, Crebolder HF: A risk model for the prediction of recurrent falls in community-dwelling elderly: a prospective cohort study. J Clin Epidemiol 2002, 55(11):1088-1094.
• [54]Ainsworth BE, Haskell WL, Leon AS, Jacobs DR Jr, Montoye HJ, Sallis JF, Paffenbarger RS Jr: Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 1993, 25(1):71-80.
• [55]Kristal AR, Feng Z, Coates RJ, Oberman A, George V: Associations of race/ethnicity, education, and dietary intervention with the validity and reliability of a food frequency questionnaire: the Women's Health Trial Feasibility Study in Minority Populations. Am J Epidemiol 1997, 146(10):856-869.
• [56]Ware JE Jr, Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992, 30(6):473-483.
• [57]Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z: Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative. Arch Intern Med 2010, 170(9):765-771.
• [58]LaCroix AZ, Cauley JA, Pettinger M, Hsia J, Bauer DC, McGowan J, Chen Z, Lewis CE, McNeeley SG, Passaro MD: Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women's Health Initiative Observational Study. Ann Intern Med 2003, 139(2):97-104.
• [59]Cumming RG, Miller JP, Kelsey JL, Davis P, Arfken CL, Birge SJ, Peck WA: Medications and multiple falls in elderly people: the St Louis OASIS study. Age Ageing 1991, 20(6):455-461.
• [60]Lavsa SM, Fabian TJ, Saul MI, Corman SL, Coley KC: Influence of medications and diagnoses on fall risk in psychiatric inpatients. Am J Health Syst Pharm 2010, 67(15):1274-1280.
• [61]Sandhu HS, Gilles E, DeVita MV, Panagopoulos G, Michelis MF: Hyponatremia associated with large-bone fracture in elderly patients. Int Urol Nephrol 2009, 41(3):733-737.
• [62]Gross P: Treatment of hyponatremia. Intern Med 2008, 47(10):885-891.
• [63]Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G: Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006, 119(1):71 e71-78.
• [64]Shumway-Cook A, Ciol MA, Hoffman J, Dudgeon BJ, Yorkston K, Chan L: Falls in the Medicare population: incidence, associated factors, and impact on health care. Phys Ther 2009, 89(4):324-332.
• [65]Robbins J, Aragaki AK, Kooperberg C, Watts N, Wactawski-Wende J, Jackson RD, LeBoff MS, Lewis CE, Chen Z, Stefanick ML: Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA 2007, 298(20):2389-2398.
• [66]Bea JW, Zhao Q, Cauley JA, LaCroix AZ, Bassford T, Lewis CE, Jackson RD, Tylavsky FA, Chen Z: Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women's Health Initiative hormone trials. Menopause 2011, 18(1):44-52.