- Email: [email protected]
Osteoporosis: New Treatments
JAMDA 16 (2015) 265e267
JAMDA journal homepage: www.jamda.com
Editorial
Osteoporosis: New Treatments John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St Louis, MO
Approximately 70% to 80% of residents in nursing homes have osteoporosis.1e3 In this issue of the Journal, Zarowitz et al4 point out that 10.8% of residents in US nursing homes have a hip fracture and 15.8% have other fractures. In persons with hip fracture, the risk of a second hip fracture is 10%.5 This is associated with a marked increased risk in mortality. Residents receiving bisphosphonates had a significantly reduced risk of mortality. Residents with dementia are at a higher risk of hip fracture than other residents.6 Pelvic fracture rates are also high in nursing homes.7 Fractures markedly increase costs of care mainly due to hospitalization costs8,9 and lead to a deterioration in functional status.10,11 Orthogeriatric models have reduced the need for nursing home placement.12 Curtis et al13 found that the 5-year risk of a second fracture was not as high as the risk of death from other causes, but nevertheless felt that as the number needed to treat to prevent a second hip fracture approximated 1, it was reasonable to use prevention approaches to reduce a second fracture.13 The feasibility of treating osteoporosis in nursing homes was demonstrated by the Vitamin D and Osteoporosis Study (ViDOS).14 Despite this evidence, only one-third of nursing home residents at risk for hip fracture were treated.4 In addition, a number of these patients were receiving calcitonin or raloxifene, which are not as efficacious as alendronate or zolendronic acid.15,16 There is a large amount of evidence that vitamin D levels in nursing home residents is low and a combination of calcium and vitamin D can reduce hip fractures in nursing home residents.11,17e19 Vitamin D deficiency is pandemic in nursing homes.20,21 Vitamin D should be limited to 1000 IU daily and calcium or yogurt should be given just before bed for optimum replacement.22,23 Too high a calcium replacement is associated with cardiovascular disease.24,25 There is an epidemic of sarcopenia among older persons.26e36 This increases the propensity of older persons to fall.37e44 Resistance exercise has been shown to improve strength40,45e51 and in patients with hip fracture to remarkably improve outcomes.52 Loss of muscle reduces mechanical loading, thus reducing bone formation.53 This has led to the concept of osteosarcopenia being doubly hazardous for the development of fractures.54e59 A major risk factor for osteosarcopenia in older persons is weight loss and malnutrition.60e69 The SARC-F questionnaire has been shown to be an excellent screening tool for sarcopenia.70
* Address correspondence to John E. Morley, MB, BCh, Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, M238, St Louis, MO 63104. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jamda.2015.02.001 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
In preventing further bone loss, it is important to avoid selective serotonin reuptake inhibitors (SSRIs),71e73 thiazolidinediones,74,75 and proton pump inhibitors (PPIs).76 These 3 drugs are all associated with calcium loss from bone, which leads to hip fractures. Two of these drugs produce hyponatremia: SSRIs and PPIs. There is evidence that hyponatremia increases hip fracture and osteoporosis. 77,78 Hyponatremia also increases the chance of developing delirium and poor mobility, further increasing the chance of falls and hip fracture.79e83 Diabetic individuals have poor-quality bone and sarcopenia and also often have hyponatremia, placing them at high risk for developing osteosarcoma.84e87 Although bisphosphonates have been the cornerstone of treatment for osteoporosis, a number of newer drugs are now becoming available.88 The first of these was denosumab.89 It is as effective as alendronate and can be given as an injection twice a year. As such, it competes with zolendronic acid, which can be given as an intravenous injection yearly. Zolendronic acid is cheaper than denosumab. The side effects of denosumab are osteonecrosis of the jaw, pancreatitis, skin rashes, and serious infections. In the original studies, it was shown to have a borderline increase in malignancies. Strontium ranelate is available in Europe and at some health food stores. It reduces nonvertebral fractures by 19% and vertebral fractures by 41%.90,91 However, in postmarketing surveillance, it increases myocardial infarction and stroke. Teriparatide (PTH1-34) decreases fractures and is recommended when the bone mineral density is less than 3.0.92 It is very expensive and can only be taken for a maximum of 2 years because it produces osteosarcoma in rodents. The most exciting drug on the horizon is romosozumab (an antibody to sclerostin). Sclerostin blocks the formation of osteoblasts. Romosozumab increases bone mineral density at the hip and lumbar spine much more than any other drug.93 A caution about long-term use is the adults who lack sclerostin (Von Buchern disease) developed very distorted facial features. Merck has developed odanacatib, a cathepsin K inhibitor. Cathepsin causes bone matrix degradation.94 Odanacatib increases bone mineral density at lumbar spine and hip. Its potential side effects are morphea and some cardiovascular side effects. Testosterone has been shown to increase bone mineral density and also increases muscle strength.95,96 Recent studies have questioned whether it increases cardiovascular disease. Despite this, it would seem to have a potential role in some older persons with muscle loss and a high propensity to fracture.97 Overall, it would appear that there is a need to increase the awareness and treatment of osteosarcopenia in nursing homes
266
Editorial / JAMDA 16 (2015) 265e267
Table 1 Drugs to Treat Osteoporosis: Past, Present, and Future
Calcium/yogurt Vitamin D (Estrogen)/Raloxifene Bisphosphonates - Alendronate - Risedronate - Ibandronate - Zoledronic acid Denosumab Teriparatide Strontium ranelate Romosozumab (sclerostin antibody) Odanacatib (cathepsin K inhibitor)
(Table 1). As recommended by the International Association of Gerontology and Geriatrics, there is a need to increase research in nursing homes on falls and fractures and their prevention.98,99 References 1. Zimmerman SI, Girman CJ, Buie VC, et al. The prevalence of osteoporosis in nursing home residents. Osteoporosis Int 1999;9:151e157. 2. Chandler JM, Zimmerman SI, Girman C, et al. Low bone mineral density and risk of fracture in white female nursing home residents. JAMA 2000;284: 972e977. 3. Gloth FM 3rd, Simonson W. Osteoporosis is underdiagnosed in skilled nursing facilities: A large-scale heel BMD screening study. J Am Med Dir Assoc 2008;9: 190e193. 4. Zarowitz BJ, Cheng LI, Allen C, et al. Osteoporosis prevalence and characteristics of treated and untreated nursing home residents with osteoporosis. J Am Med Dir Assoc 2015;16:341e348. 5. Shen SH, Huang KC, Tsai YH, et al. Risk analysis for second hip fracture in patients after hip fracture surgery: A nationwide population-based study. J Am Med Dir Assoc 2014;15:725e731. 6. Toot S, Devine M, Akporobaro A, Orrell M. Causes of hospital admission for people with dementia: A systematic review and meta-analysis. J Am Med Dir Assoc 2013;14:463e470. 7. Benzinger P, Becker C, Kerse N, et al. Pelvic fracture rates in community-living people with and without disability and in residents of nursing homes. J Am Med Dir Assoc 2013;14:673e678. 8. Zimmerman S, Chandler JM, Hawkes W, et al. Effect of fracture on the health care use of nursing home residents. Arch Intern Med 2002;162:1502e1508. 9. Singer A, Spangler L, O’Malley CD, et al. Hospitalization burden for osteoporotic fracture and other serious disease in older US women. Osteoporosis Int 2014; 25:S505. 10. Osnes EK, Lofthus CM, Meyer HE, et al. Consequences of hip fracture on activities of daily life and residential needs. Osteoporos Int 2004;15:567e574. 11. Morley JE. Hip fractures. J Am Med Dir Assoc 2010;11:81e83. 12. Martinez-Reig M, Ahmad L, Duque G. The orthogeriatric model of care: Systematic review of predictors of institutionalization and mortality in post-hip fracture patients and evidence for interventions. J Am Med Dir Assoc 2012; 13:770e777. 13. Curtis JR, Arora T, Matthews RS, et al. Is withholding osteoporosis medication after fracture sometimes rational? A comparison of the risk for second fracture versus death. J Am Med Dir Assoc 2010;11:584e591. 14. Kennedy CC, Thabane L, Ioannidis G, et al. Implementing a knowledge translation intervention in long-term care: Feasibility results from the Vitamin D and Osteoporosis Study (ViDOS). J Am Med Dir Assoc 2014;15:943e945. 15. Morley JE. Osteoporosis and fragility fractures. J Am Med Dir Assoc 2011;12: 389e392. 16. Duque G, Mallet L, Roberts A, et al. To treat or not to treat, that is the question: Proceedings of the Quebec symposium for the treatment of osteoporosis in long-term care institutions, Saint-Hyacinthe, Quebec, November 5, 2004. J Am Med Dir Assoc 2007;8:e67ee73. 17. Janssen HC, Emmelot-Vonk MH, Verhaar HJ, van der Schouw YT. Vitamin D and muscle function: Is there a threshold in the relation? J Am Med Dir Assoc 2013; 14:627.e13e627.e18. 18. Islam T, Peiris P, Copeland RJ, et al. Vitamin D: Lessons from the veterans population. J Am Med Dir Assoc 2011;12:257e262. 19. Faulhaber GA, Schulz LF, Furlanetto TW. Vitamin D status and ICU outcomes: Potential confounders. J Am Med Dir Assoc 2011;12:e1ee2. 20. Demontiero O, Herrmann M, Duque G. Supplementation with vitamin D and calcium in long-term care residents. J Am Med Dir Assoc 2011;12:190e194. 21. Hamid Z, Riggs A, Spencer T, et al. Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D. J Am Med Dir Assoc 2007;8:71e75.
22. Morley JE. Vitamin D redux. J Am Med Dir Assoc 2009;10:591e592. 23. Morley JE. Should all long-term care residents receive vitamin D? J Am Med Dir Assoc 2007;8:69e70. 24. Michaëlsson K, Melhus H, Warensjö Lemming E, et al. Long term calcium intake and rates of all cause and cardiovascular mortality: Community based prospective longitudinal cohort study. BMJ 2013;346:f228. 25. Reid IR, Bristow SM, Bolland MJ. Cardiovascular complications of calcium supplements. J Cell Biochem 2015;116:494e501. 26. Cao L, Chen S, Zou C, et al. A pilot study of the SARC-F scale on screening sarcopenia and physical disability in the Chinese older people. J Nutr Health Aging 2014;18:277e283. 27. Morley JE. Sarcopenia: Diagnosis and treatment. J Nutr Health Aging 2008;12: 452e456. 28. Rossi AP, Fantin F, Micciolo R, et al. Identifying sarcopenia in acute care setting patients. J Am Med Dir Assoc 2014;15:303.e7e303.e12. 29. Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 2014;15:95e101. 30. Yamada M, Nishiguchi S, Fukutani N, et al. Prevalence of sarcopenia in community-dwelling Japanese older adults. J Am Med Dir Assoc 2013;14: 911e915. 31. Woo J, Leung J, Morley JE. Defining sarcopenia in terms of incident adverse outcomes. J Am Med Dir Assoc 2015;16:247e252. 32. Kim H, Suzuki T, Kim M, et al. Incidence and predictors of sarcopenia onset in community-dwelling elderly Japanese women: 4-year follow-up study. J Am Med Dir Assoc 2015;16:85.e1e85.e8. 33. Landi F, Martone AM, Calvani R, Marzetti E. Sarcopenia risk screening tool: A new strategy for clinical practice. J Am Med Dir Assoc 2014;15:613e614. 34. Lee WJ, Liu LK, Peng LN, et al, ILAS Research Group. Comparisons of sarcopenia defined by IWGS and EWGSOP criteria among older people: Results from the I-Lan longitudinal aging study. J Am Med Dir Assoc 2013;14:528.e1e528.e7. 35. Coin A, Sarti S, Ruggiero E, et al. Prevalence of sarcopenia based on different diagnostic criteria using DEXAS and appendicular skeletal muscle mass reference values in an Italian population aged 20 to 80. J Am Med Dir Assoc 2013; 14:507e512. 36. Roman D, Mahoney K, Mohamadi A. Sarcopenia: What’s in a name? J Am Med Dir Assoc 2013;14:80e82. 37. Buchele G, Becker C, Cameron ID, et al. Predictors of serious consequences of falls in residential aged care: Analysis of more than 70,000 falls from residents of Bavarian nursing homes. J Am Med Dir Assoc 2014;15:559e563. 38. Morley JE. Falls and fractures. J Am Med Dir Assoc 2007;8:276e278. 39. Morley JE. Frailty, falls, and fractures. J Am Med Dir Assoc 2013;14:149e151. 40. Silva RB, Eslick GD, Duque G. Exercise for falls and fracture prevention in long term care facilities: A systematic review and meta-analysis. J Am Med Dir Assoc 2013;14:685e689.e2. 41. Rochat S, Monod S, Seematter-Bagnoud L, et al. Fallers in postacute rehabilitation have worse functional recovery and increased health services use. J Am Med Dir Assoc 2013;14:832e836. 42. Kurita N, Horie S, Yamazaki S, et al. Low testosterone levels, depressive symptoms, and falls in older men: A cross-sectional study. J Am Med Dir Assoc 2014;15:30e35. 43. Ogama N, Sakurai T, Shimizu A, Toba K. Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and Alzheimer’s disease. J Am Med Dir Assoc 2014;15:36e41. 44. Morley JE, Rolland Y, Tolson D, Velals B. Increasing awareness of the factors producing falls: The mini falls assessment. J Am Med Dir Assoc 2012;13: 87e90. 45. Landi F, Onder G, Bernabei R. Sarcopenia and diabetes: Two sides of the same coin. J Am Med Dir Assoc 2013;14:540e541. 46. Gryson C, Ratel S, Rance M, et al. Four-month course of soluble milk proteins interacts with exercise to improve muscle strength and delay fatigue in elderly participants. J Am Med Dir Assoc 2014;15:958.e1e958.e9. 47. Valenzuela T. Efficacy of progressive resistance training interventions in older adults in nursing homes: A systematic review. J Am Med Dir Assoc 2012;13: 418e428. 48. Tieland M, Dirks ML, van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: A randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:713e719. 49. Paddon-Jones D. Perspective: Exercise and protein supplementation in frail elders. J Am Med Dir Assoc 2013;14:73e74. 50. Brienesse LA, Emerson MN. Effects of resistance training for people with Parkinson’s disease: A systematic review. J Am Med Dir Assoc 2013;14:236e241. 51. Cadore EL, Izquierdo M. New strategies for the concurrent strength-, power-, and endurance-training prescription in elderly individuals. J Am Med Dir Assoc 2013;14:623e624. 52. Singh NA, Quine S, Clemson LM, et al. Effects of high-intensity progressive resistance training and targeted multidisciplinary treatment of frailty on mortality and nursing home admissions after hip fracture: A randomized controlled trial. J Am Med Dir Assoc 2012;13:24e30. 53. Morse A, McDonald MM, Kelly NH, et al. Mechanical load increases in bone formation via a sclerostin-independent pathway. J Bone Miner Res 2014;29: 2456e2467. 54. Huo YR, Suriyaarachchi P, Gomez F, et al. Phenotype of osteosarcopenia in older individuals with a history of falling. J Am Med Dir Assoc 2015;16: 290e295.
Editorial / JAMDA 16 (2015) 265e267 55. Yu R, Leung J, Woo J. Incremental predictive value of sarcopenia for incident fracture in an elderly Chinese cohort: Results from the Osteoporotic Fractures in Men (MrOs) Study. J Am Med Dir Assoc 2014;15:551e558. 56. Yu R, Leung J, Woo J. Sarcopenia combined with FRAX probabilities improves fracture risk prediction in older Chinese men. J Am Med Dir Assoc 2014;15: 918e923. 57. Cederholm T, Morley JE. Sarcopenia: The new definitions. Curr Opin Clin Nutr Metab Care 2015;18:1e4. 58. Formiga F, Ferrer A, Padros G, et al. Diabetes mellitus as a risk factor for functional and cognitive decline in very old people: The Octabaix study. J Am Med Dir Assoc 2014;15:924e928. 59. Hita-Contreras F, Martinez-Amat A, Cruz-Diaz D, Perez-Lopez FR. Osteosarcopenia obesity and fall prevention strategies. Maturitas 2015;80: 126e132. 60. Tamura BK, Bell CL, Masaki KH, Amella EJ. Factors associated with weight loss, low BMI, and malnutrition among nursing home patients: A systematic review of the literature. J Am Med Dir Assoc 2013;14:649e655. 61. Soenen S, Chapman IM. Body weight, anorexia, and undernutrition in older people. J Am Med Dir Assoc 2013;14:642e648. 62. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637e3647. 63. Morley JE. Anorexia of aging: A true geriatric syndrome. J Nutr Health Aging 2012;16:422e425. 64. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229e230. 65. Von Haehling S, Morley JE, Anker SD. From muscle wasting to sarcopenia and myopenia: Update 2012. J Cachexia Sarcopenia Muscle 2012;3:213e217. 66. Morley JE, von Haehling S, Anker SD, Vellas B. From sarcopenia to frailty: A road less traveled. J Cachexia Sarcopenia Muscle 2014;5:5e8. 67. Morley JE. Pathophysiology of the anorexia of aging. Curr Opin Clin Nutr Metab Care 2013;16:27e32. 68. Bell CL, Tamura BK, Masaki KH, Amella EJ. Prevalence and measures of nutritional compromise among nursing home patients: Weight loss, low body mass index, malnutrition, and feeding dependency, a systematic review of the literature. J Am Med Dir Assoc 2013;14:94e100. 69. Morley JE. Undernutrition: A major problem in nursing homes. J Am Med Dir Assoc 2011;12:243e246. 70. Woo J, Leung J, Morley JE. Validating the SARC-F: A suitable community screening tool for sarcopenia? J Am Med Dir Assoc 2014;15:630e634. 71. Chen F, Hahn TJ, Weintraub NT. Do SSRIs play a role in decreasing bone mineral density? J Am Med Dir Assoc 2012;13:413e417. 72. Iraqi A, Baickle E. A case report of hyponatremia with citalopram use. J Am Med Dir Assoc 2004;5:64e65. 73. Morley JE. Depression in nursing home residents. J Am Med Dir Assoc 2010;11: 301e303. 74. Grey A. Diabetes medications and bone. Curr Osteoporos Rep 2015;13: 35e40. 75. Zhu ZN, Jiang YF, Ding T. Risk of fracture with thiazolidinediones: An updated meta-analysis of randomized clinical trials. Bone 2014;68:115e123. 76. Leontiadis GI, Moayyedi P. Proton pump inhibitors and risk of bone fractures. Curr Treat Options Gastroenterol 2014;12:414e423. 77. Jamal SA, Arampatzis S, Harrison SL, et al. Hyponatremia and fractures: Findings from the Osteoporotic Fractures in Men study. J Bone Miner Res; 2014 Oct 7 [Epub ahead of print]. 78. Cumming K, Hoyle GE, Hutchison JD, Soiza RL. Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures. PLoS One 2014;9:e88272.
267
79. Uriz-Otano F, Uriz-Otano JI, Malafarina V. Factors associated with short-term functional recovery in elderly people with a hip fracture. Influence of cognitive impairment. J Am Med Dir Assoc 2015;16:215e220. 80. Rudolph JL, Archambault E, Kelly B. VA Boston Delirium Task Force. A delirium risk modification program is associated with hospital outcomes. J Am Med Dir Assoc 2014;15:957.e7e957.e11. 81. Flaherty JH, Morley JE. Delirium in the nursing home. J Am Med Dir Assoc 2008; 9:157e161. 82. Eeles E, Rockwood K. Delirium in the long-term care setting: Clinical and research challenges. J Am Med Dir Assoc 2008;9:157e161. 83. Rockwood K. Making delirium prevention acceptable in nursing homes. J Am Med Dir Assoc 2014;15:6e7. 84. Leenders M, Verdijk LB, van der Hoeven L, et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14:585e592. 85. Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc 2014;15:853e859. 86. Sinclair A, Morley JE, Rodriguez-Manas L, et al. Diabetes mellitus in older people: Position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force on Experts in Diabetes. J Am Med Dir Assoc 2012;13:497e502. 87. Mallery LH, Ransom T, Steeves B, et al. Evidence-informed guidelines for treating frail older adults with type 2 diabetes: From the Diabetes Care Program of Nova Scotia (DCPNS) and the Palliative Therapeutic Harmonization (PATH) program. J Am Med Dir Assoc 2013;14:801e808. 88. Bernabei R, Martone AM, Ortolani E, et al. Screening, diagnosis and treatment of osteoporosis: A brief review. Clin Cases Miner Bone Metab 2014;11:201e207. 89. Narayanan P. Denosumab: A comprehensive review. South Asian J Cancer 2013;2:272e277. 90. Cianferotti L, D’Asta F, Brandi ML. A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis. Ther Adv Musculoskelet Dis 2013;5:127e139. 91. Reginster JY. Cardiac concerns associated with strontium ranelate. Expert Opin Drug Saf 2014;13:1209e1213. 92. Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: An updated systematic review. Ann Intern Med 2014;161:711e723. 93. Yavropoulou MP, Xygonakis C, Lolou M, et al. The sclerostin story: From human genetics to the development of novel anabolic treatment for osteoporosis. Hormones (Athens) 2014;13:323e337. 94. Bone HG, Dempster DW, Eisman JA, et al. Odanacatib for the treatment of postmenopausal osteoporosis: Development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos Int 2015;26:699e712. 95. Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503e510. 96. Morley JE. Scientific overview of hormone treatment used for rejuvenation. Fertil Steril 2013;99:1807e1813. 97. Morley JE. Hypogonadism, testosterone, and nursing home residents. J Am Med Dir Assoc 2013;14:381e383. 98. Morley JE, Caplan G, Cesari M, et al. International survey of nursing home resident priorities. J Am Med Dir Assoc 2014;15:309e312. 99. Tolson D, Rolland Y, Andrieu S, et al. International Association of Gerontology and Geriatrics: A global agenda for clinical research and quality of care in nursing homes. J Am Med Dir Assoc 2011;12:184e189.
JAMDA journal homepage: www.jamda.com
Editorial
Osteoporosis: New Treatments John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St Louis, MO
Approximately 70% to 80% of residents in nursing homes have osteoporosis.1e3 In this issue of the Journal, Zarowitz et al4 point out that 10.8% of residents in US nursing homes have a hip fracture and 15.8% have other fractures. In persons with hip fracture, the risk of a second hip fracture is 10%.5 This is associated with a marked increased risk in mortality. Residents receiving bisphosphonates had a significantly reduced risk of mortality. Residents with dementia are at a higher risk of hip fracture than other residents.6 Pelvic fracture rates are also high in nursing homes.7 Fractures markedly increase costs of care mainly due to hospitalization costs8,9 and lead to a deterioration in functional status.10,11 Orthogeriatric models have reduced the need for nursing home placement.12 Curtis et al13 found that the 5-year risk of a second fracture was not as high as the risk of death from other causes, but nevertheless felt that as the number needed to treat to prevent a second hip fracture approximated 1, it was reasonable to use prevention approaches to reduce a second fracture.13 The feasibility of treating osteoporosis in nursing homes was demonstrated by the Vitamin D and Osteoporosis Study (ViDOS).14 Despite this evidence, only one-third of nursing home residents at risk for hip fracture were treated.4 In addition, a number of these patients were receiving calcitonin or raloxifene, which are not as efficacious as alendronate or zolendronic acid.15,16 There is a large amount of evidence that vitamin D levels in nursing home residents is low and a combination of calcium and vitamin D can reduce hip fractures in nursing home residents.11,17e19 Vitamin D deficiency is pandemic in nursing homes.20,21 Vitamin D should be limited to 1000 IU daily and calcium or yogurt should be given just before bed for optimum replacement.22,23 Too high a calcium replacement is associated with cardiovascular disease.24,25 There is an epidemic of sarcopenia among older persons.26e36 This increases the propensity of older persons to fall.37e44 Resistance exercise has been shown to improve strength40,45e51 and in patients with hip fracture to remarkably improve outcomes.52 Loss of muscle reduces mechanical loading, thus reducing bone formation.53 This has led to the concept of osteosarcopenia being doubly hazardous for the development of fractures.54e59 A major risk factor for osteosarcopenia in older persons is weight loss and malnutrition.60e69 The SARC-F questionnaire has been shown to be an excellent screening tool for sarcopenia.70
* Address correspondence to John E. Morley, MB, BCh, Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, M238, St Louis, MO 63104. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jamda.2015.02.001 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
In preventing further bone loss, it is important to avoid selective serotonin reuptake inhibitors (SSRIs),71e73 thiazolidinediones,74,75 and proton pump inhibitors (PPIs).76 These 3 drugs are all associated with calcium loss from bone, which leads to hip fractures. Two of these drugs produce hyponatremia: SSRIs and PPIs. There is evidence that hyponatremia increases hip fracture and osteoporosis. 77,78 Hyponatremia also increases the chance of developing delirium and poor mobility, further increasing the chance of falls and hip fracture.79e83 Diabetic individuals have poor-quality bone and sarcopenia and also often have hyponatremia, placing them at high risk for developing osteosarcoma.84e87 Although bisphosphonates have been the cornerstone of treatment for osteoporosis, a number of newer drugs are now becoming available.88 The first of these was denosumab.89 It is as effective as alendronate and can be given as an injection twice a year. As such, it competes with zolendronic acid, which can be given as an intravenous injection yearly. Zolendronic acid is cheaper than denosumab. The side effects of denosumab are osteonecrosis of the jaw, pancreatitis, skin rashes, and serious infections. In the original studies, it was shown to have a borderline increase in malignancies. Strontium ranelate is available in Europe and at some health food stores. It reduces nonvertebral fractures by 19% and vertebral fractures by 41%.90,91 However, in postmarketing surveillance, it increases myocardial infarction and stroke. Teriparatide (PTH1-34) decreases fractures and is recommended when the bone mineral density is less than 3.0.92 It is very expensive and can only be taken for a maximum of 2 years because it produces osteosarcoma in rodents. The most exciting drug on the horizon is romosozumab (an antibody to sclerostin). Sclerostin blocks the formation of osteoblasts. Romosozumab increases bone mineral density at the hip and lumbar spine much more than any other drug.93 A caution about long-term use is the adults who lack sclerostin (Von Buchern disease) developed very distorted facial features. Merck has developed odanacatib, a cathepsin K inhibitor. Cathepsin causes bone matrix degradation.94 Odanacatib increases bone mineral density at lumbar spine and hip. Its potential side effects are morphea and some cardiovascular side effects. Testosterone has been shown to increase bone mineral density and also increases muscle strength.95,96 Recent studies have questioned whether it increases cardiovascular disease. Despite this, it would seem to have a potential role in some older persons with muscle loss and a high propensity to fracture.97 Overall, it would appear that there is a need to increase the awareness and treatment of osteosarcopenia in nursing homes
266
Editorial / JAMDA 16 (2015) 265e267
Table 1 Drugs to Treat Osteoporosis: Past, Present, and Future
Calcium/yogurt Vitamin D (Estrogen)/Raloxifene Bisphosphonates - Alendronate - Risedronate - Ibandronate - Zoledronic acid Denosumab Teriparatide Strontium ranelate Romosozumab (sclerostin antibody) Odanacatib (cathepsin K inhibitor)
(Table 1). As recommended by the International Association of Gerontology and Geriatrics, there is a need to increase research in nursing homes on falls and fractures and their prevention.98,99 References 1. Zimmerman SI, Girman CJ, Buie VC, et al. The prevalence of osteoporosis in nursing home residents. Osteoporosis Int 1999;9:151e157. 2. Chandler JM, Zimmerman SI, Girman C, et al. Low bone mineral density and risk of fracture in white female nursing home residents. JAMA 2000;284: 972e977. 3. Gloth FM 3rd, Simonson W. Osteoporosis is underdiagnosed in skilled nursing facilities: A large-scale heel BMD screening study. J Am Med Dir Assoc 2008;9: 190e193. 4. Zarowitz BJ, Cheng LI, Allen C, et al. Osteoporosis prevalence and characteristics of treated and untreated nursing home residents with osteoporosis. J Am Med Dir Assoc 2015;16:341e348. 5. Shen SH, Huang KC, Tsai YH, et al. Risk analysis for second hip fracture in patients after hip fracture surgery: A nationwide population-based study. J Am Med Dir Assoc 2014;15:725e731. 6. Toot S, Devine M, Akporobaro A, Orrell M. Causes of hospital admission for people with dementia: A systematic review and meta-analysis. J Am Med Dir Assoc 2013;14:463e470. 7. Benzinger P, Becker C, Kerse N, et al. Pelvic fracture rates in community-living people with and without disability and in residents of nursing homes. J Am Med Dir Assoc 2013;14:673e678. 8. Zimmerman S, Chandler JM, Hawkes W, et al. Effect of fracture on the health care use of nursing home residents. Arch Intern Med 2002;162:1502e1508. 9. Singer A, Spangler L, O’Malley CD, et al. Hospitalization burden for osteoporotic fracture and other serious disease in older US women. Osteoporosis Int 2014; 25:S505. 10. Osnes EK, Lofthus CM, Meyer HE, et al. Consequences of hip fracture on activities of daily life and residential needs. Osteoporos Int 2004;15:567e574. 11. Morley JE. Hip fractures. J Am Med Dir Assoc 2010;11:81e83. 12. Martinez-Reig M, Ahmad L, Duque G. The orthogeriatric model of care: Systematic review of predictors of institutionalization and mortality in post-hip fracture patients and evidence for interventions. J Am Med Dir Assoc 2012; 13:770e777. 13. Curtis JR, Arora T, Matthews RS, et al. Is withholding osteoporosis medication after fracture sometimes rational? A comparison of the risk for second fracture versus death. J Am Med Dir Assoc 2010;11:584e591. 14. Kennedy CC, Thabane L, Ioannidis G, et al. Implementing a knowledge translation intervention in long-term care: Feasibility results from the Vitamin D and Osteoporosis Study (ViDOS). J Am Med Dir Assoc 2014;15:943e945. 15. Morley JE. Osteoporosis and fragility fractures. J Am Med Dir Assoc 2011;12: 389e392. 16. Duque G, Mallet L, Roberts A, et al. To treat or not to treat, that is the question: Proceedings of the Quebec symposium for the treatment of osteoporosis in long-term care institutions, Saint-Hyacinthe, Quebec, November 5, 2004. J Am Med Dir Assoc 2007;8:e67ee73. 17. Janssen HC, Emmelot-Vonk MH, Verhaar HJ, van der Schouw YT. Vitamin D and muscle function: Is there a threshold in the relation? J Am Med Dir Assoc 2013; 14:627.e13e627.e18. 18. Islam T, Peiris P, Copeland RJ, et al. Vitamin D: Lessons from the veterans population. J Am Med Dir Assoc 2011;12:257e262. 19. Faulhaber GA, Schulz LF, Furlanetto TW. Vitamin D status and ICU outcomes: Potential confounders. J Am Med Dir Assoc 2011;12:e1ee2. 20. Demontiero O, Herrmann M, Duque G. Supplementation with vitamin D and calcium in long-term care residents. J Am Med Dir Assoc 2011;12:190e194. 21. Hamid Z, Riggs A, Spencer T, et al. Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D. J Am Med Dir Assoc 2007;8:71e75.
22. Morley JE. Vitamin D redux. J Am Med Dir Assoc 2009;10:591e592. 23. Morley JE. Should all long-term care residents receive vitamin D? J Am Med Dir Assoc 2007;8:69e70. 24. Michaëlsson K, Melhus H, Warensjö Lemming E, et al. Long term calcium intake and rates of all cause and cardiovascular mortality: Community based prospective longitudinal cohort study. BMJ 2013;346:f228. 25. Reid IR, Bristow SM, Bolland MJ. Cardiovascular complications of calcium supplements. J Cell Biochem 2015;116:494e501. 26. Cao L, Chen S, Zou C, et al. A pilot study of the SARC-F scale on screening sarcopenia and physical disability in the Chinese older people. J Nutr Health Aging 2014;18:277e283. 27. Morley JE. Sarcopenia: Diagnosis and treatment. J Nutr Health Aging 2008;12: 452e456. 28. Rossi AP, Fantin F, Micciolo R, et al. Identifying sarcopenia in acute care setting patients. J Am Med Dir Assoc 2014;15:303.e7e303.e12. 29. Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 2014;15:95e101. 30. Yamada M, Nishiguchi S, Fukutani N, et al. Prevalence of sarcopenia in community-dwelling Japanese older adults. J Am Med Dir Assoc 2013;14: 911e915. 31. Woo J, Leung J, Morley JE. Defining sarcopenia in terms of incident adverse outcomes. J Am Med Dir Assoc 2015;16:247e252. 32. Kim H, Suzuki T, Kim M, et al. Incidence and predictors of sarcopenia onset in community-dwelling elderly Japanese women: 4-year follow-up study. J Am Med Dir Assoc 2015;16:85.e1e85.e8. 33. Landi F, Martone AM, Calvani R, Marzetti E. Sarcopenia risk screening tool: A new strategy for clinical practice. J Am Med Dir Assoc 2014;15:613e614. 34. Lee WJ, Liu LK, Peng LN, et al, ILAS Research Group. Comparisons of sarcopenia defined by IWGS and EWGSOP criteria among older people: Results from the I-Lan longitudinal aging study. J Am Med Dir Assoc 2013;14:528.e1e528.e7. 35. Coin A, Sarti S, Ruggiero E, et al. Prevalence of sarcopenia based on different diagnostic criteria using DEXAS and appendicular skeletal muscle mass reference values in an Italian population aged 20 to 80. J Am Med Dir Assoc 2013; 14:507e512. 36. Roman D, Mahoney K, Mohamadi A. Sarcopenia: What’s in a name? J Am Med Dir Assoc 2013;14:80e82. 37. Buchele G, Becker C, Cameron ID, et al. Predictors of serious consequences of falls in residential aged care: Analysis of more than 70,000 falls from residents of Bavarian nursing homes. J Am Med Dir Assoc 2014;15:559e563. 38. Morley JE. Falls and fractures. J Am Med Dir Assoc 2007;8:276e278. 39. Morley JE. Frailty, falls, and fractures. J Am Med Dir Assoc 2013;14:149e151. 40. Silva RB, Eslick GD, Duque G. Exercise for falls and fracture prevention in long term care facilities: A systematic review and meta-analysis. J Am Med Dir Assoc 2013;14:685e689.e2. 41. Rochat S, Monod S, Seematter-Bagnoud L, et al. Fallers in postacute rehabilitation have worse functional recovery and increased health services use. J Am Med Dir Assoc 2013;14:832e836. 42. Kurita N, Horie S, Yamazaki S, et al. Low testosterone levels, depressive symptoms, and falls in older men: A cross-sectional study. J Am Med Dir Assoc 2014;15:30e35. 43. Ogama N, Sakurai T, Shimizu A, Toba K. Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and Alzheimer’s disease. J Am Med Dir Assoc 2014;15:36e41. 44. Morley JE, Rolland Y, Tolson D, Velals B. Increasing awareness of the factors producing falls: The mini falls assessment. J Am Med Dir Assoc 2012;13: 87e90. 45. Landi F, Onder G, Bernabei R. Sarcopenia and diabetes: Two sides of the same coin. J Am Med Dir Assoc 2013;14:540e541. 46. Gryson C, Ratel S, Rance M, et al. Four-month course of soluble milk proteins interacts with exercise to improve muscle strength and delay fatigue in elderly participants. J Am Med Dir Assoc 2014;15:958.e1e958.e9. 47. Valenzuela T. Efficacy of progressive resistance training interventions in older adults in nursing homes: A systematic review. J Am Med Dir Assoc 2012;13: 418e428. 48. Tieland M, Dirks ML, van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: A randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:713e719. 49. Paddon-Jones D. Perspective: Exercise and protein supplementation in frail elders. J Am Med Dir Assoc 2013;14:73e74. 50. Brienesse LA, Emerson MN. Effects of resistance training for people with Parkinson’s disease: A systematic review. J Am Med Dir Assoc 2013;14:236e241. 51. Cadore EL, Izquierdo M. New strategies for the concurrent strength-, power-, and endurance-training prescription in elderly individuals. J Am Med Dir Assoc 2013;14:623e624. 52. Singh NA, Quine S, Clemson LM, et al. Effects of high-intensity progressive resistance training and targeted multidisciplinary treatment of frailty on mortality and nursing home admissions after hip fracture: A randomized controlled trial. J Am Med Dir Assoc 2012;13:24e30. 53. Morse A, McDonald MM, Kelly NH, et al. Mechanical load increases in bone formation via a sclerostin-independent pathway. J Bone Miner Res 2014;29: 2456e2467. 54. Huo YR, Suriyaarachchi P, Gomez F, et al. Phenotype of osteosarcopenia in older individuals with a history of falling. J Am Med Dir Assoc 2015;16: 290e295.
Editorial / JAMDA 16 (2015) 265e267 55. Yu R, Leung J, Woo J. Incremental predictive value of sarcopenia for incident fracture in an elderly Chinese cohort: Results from the Osteoporotic Fractures in Men (MrOs) Study. J Am Med Dir Assoc 2014;15:551e558. 56. Yu R, Leung J, Woo J. Sarcopenia combined with FRAX probabilities improves fracture risk prediction in older Chinese men. J Am Med Dir Assoc 2014;15: 918e923. 57. Cederholm T, Morley JE. Sarcopenia: The new definitions. Curr Opin Clin Nutr Metab Care 2015;18:1e4. 58. Formiga F, Ferrer A, Padros G, et al. Diabetes mellitus as a risk factor for functional and cognitive decline in very old people: The Octabaix study. J Am Med Dir Assoc 2014;15:924e928. 59. Hita-Contreras F, Martinez-Amat A, Cruz-Diaz D, Perez-Lopez FR. Osteosarcopenia obesity and fall prevention strategies. Maturitas 2015;80: 126e132. 60. Tamura BK, Bell CL, Masaki KH, Amella EJ. Factors associated with weight loss, low BMI, and malnutrition among nursing home patients: A systematic review of the literature. J Am Med Dir Assoc 2013;14:649e655. 61. Soenen S, Chapman IM. Body weight, anorexia, and undernutrition in older people. J Am Med Dir Assoc 2013;14:642e648. 62. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637e3647. 63. Morley JE. Anorexia of aging: A true geriatric syndrome. J Nutr Health Aging 2012;16:422e425. 64. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229e230. 65. Von Haehling S, Morley JE, Anker SD. From muscle wasting to sarcopenia and myopenia: Update 2012. J Cachexia Sarcopenia Muscle 2012;3:213e217. 66. Morley JE, von Haehling S, Anker SD, Vellas B. From sarcopenia to frailty: A road less traveled. J Cachexia Sarcopenia Muscle 2014;5:5e8. 67. Morley JE. Pathophysiology of the anorexia of aging. Curr Opin Clin Nutr Metab Care 2013;16:27e32. 68. Bell CL, Tamura BK, Masaki KH, Amella EJ. Prevalence and measures of nutritional compromise among nursing home patients: Weight loss, low body mass index, malnutrition, and feeding dependency, a systematic review of the literature. J Am Med Dir Assoc 2013;14:94e100. 69. Morley JE. Undernutrition: A major problem in nursing homes. J Am Med Dir Assoc 2011;12:243e246. 70. Woo J, Leung J, Morley JE. Validating the SARC-F: A suitable community screening tool for sarcopenia? J Am Med Dir Assoc 2014;15:630e634. 71. Chen F, Hahn TJ, Weintraub NT. Do SSRIs play a role in decreasing bone mineral density? J Am Med Dir Assoc 2012;13:413e417. 72. Iraqi A, Baickle E. A case report of hyponatremia with citalopram use. J Am Med Dir Assoc 2004;5:64e65. 73. Morley JE. Depression in nursing home residents. J Am Med Dir Assoc 2010;11: 301e303. 74. Grey A. Diabetes medications and bone. Curr Osteoporos Rep 2015;13: 35e40. 75. Zhu ZN, Jiang YF, Ding T. Risk of fracture with thiazolidinediones: An updated meta-analysis of randomized clinical trials. Bone 2014;68:115e123. 76. Leontiadis GI, Moayyedi P. Proton pump inhibitors and risk of bone fractures. Curr Treat Options Gastroenterol 2014;12:414e423. 77. Jamal SA, Arampatzis S, Harrison SL, et al. Hyponatremia and fractures: Findings from the Osteoporotic Fractures in Men study. J Bone Miner Res; 2014 Oct 7 [Epub ahead of print]. 78. Cumming K, Hoyle GE, Hutchison JD, Soiza RL. Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures. PLoS One 2014;9:e88272.
267
79. Uriz-Otano F, Uriz-Otano JI, Malafarina V. Factors associated with short-term functional recovery in elderly people with a hip fracture. Influence of cognitive impairment. J Am Med Dir Assoc 2015;16:215e220. 80. Rudolph JL, Archambault E, Kelly B. VA Boston Delirium Task Force. A delirium risk modification program is associated with hospital outcomes. J Am Med Dir Assoc 2014;15:957.e7e957.e11. 81. Flaherty JH, Morley JE. Delirium in the nursing home. J Am Med Dir Assoc 2008; 9:157e161. 82. Eeles E, Rockwood K. Delirium in the long-term care setting: Clinical and research challenges. J Am Med Dir Assoc 2008;9:157e161. 83. Rockwood K. Making delirium prevention acceptable in nursing homes. J Am Med Dir Assoc 2014;15:6e7. 84. Leenders M, Verdijk LB, van der Hoeven L, et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14:585e592. 85. Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc 2014;15:853e859. 86. Sinclair A, Morley JE, Rodriguez-Manas L, et al. Diabetes mellitus in older people: Position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force on Experts in Diabetes. J Am Med Dir Assoc 2012;13:497e502. 87. Mallery LH, Ransom T, Steeves B, et al. Evidence-informed guidelines for treating frail older adults with type 2 diabetes: From the Diabetes Care Program of Nova Scotia (DCPNS) and the Palliative Therapeutic Harmonization (PATH) program. J Am Med Dir Assoc 2013;14:801e808. 88. Bernabei R, Martone AM, Ortolani E, et al. Screening, diagnosis and treatment of osteoporosis: A brief review. Clin Cases Miner Bone Metab 2014;11:201e207. 89. Narayanan P. Denosumab: A comprehensive review. South Asian J Cancer 2013;2:272e277. 90. Cianferotti L, D’Asta F, Brandi ML. A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis. Ther Adv Musculoskelet Dis 2013;5:127e139. 91. Reginster JY. Cardiac concerns associated with strontium ranelate. Expert Opin Drug Saf 2014;13:1209e1213. 92. Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: An updated systematic review. Ann Intern Med 2014;161:711e723. 93. Yavropoulou MP, Xygonakis C, Lolou M, et al. The sclerostin story: From human genetics to the development of novel anabolic treatment for osteoporosis. Hormones (Athens) 2014;13:323e337. 94. Bone HG, Dempster DW, Eisman JA, et al. Odanacatib for the treatment of postmenopausal osteoporosis: Development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos Int 2015;26:699e712. 95. Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503e510. 96. Morley JE. Scientific overview of hormone treatment used for rejuvenation. Fertil Steril 2013;99:1807e1813. 97. Morley JE. Hypogonadism, testosterone, and nursing home residents. J Am Med Dir Assoc 2013;14:381e383. 98. Morley JE, Caplan G, Cesari M, et al. International survey of nursing home resident priorities. J Am Med Dir Assoc 2014;15:309e312. 99. Tolson D, Rolland Y, Andrieu S, et al. International Association of Gerontology and Geriatrics: A global agenda for clinical research and quality of care in nursing homes. J Am Med Dir Assoc 2011;12:184e189.