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Osteoporosis: Increasing Screening and Treatment for Postmenopausal Women
The Journal for Nurse Practitioners 15 (2019) 347e350
Contents lists available at ScienceDirect
The Journal for Nurse Practitioners journal homepage: www.npjournal.org
Osteoporosis: Increasing Screening and Treatment for Postmenopausal Women Karen D. French, MSN, FNP-C, Donna Emanuele, DNP, FNP-BC a b s t r a c t Keywords: bone mineral density fracture fragility osteoporosis postmenopausal
Postmenopausal women are at risk for osteoporosis, a skeletal loss of integrity, which predisposes them to increased fall rates and both primary and secondary skeletal fractures. The risk and cost of osteoporotic fractures is greater than the risks of strokes, myocardial infarction, and breast cancer combined. With the baby boomer population reaching postmenopausal ages, the burden of care and cost will likely become prohibitive if the current rates of screening and treatment continue. Nurse practitioners are at the forefront of the primary prevention of osteoporotic fractures, in addition to having the skill and education to manage the osteoporotic patient. © 2019 Elsevier Inc. All rights reserved.
Physical skeletal loss of integrity predisposes women to increased fall rates, with resultant skeletal fractures. Every 3 seconds, someone suffers an osteoporotic fracture.1 Osteoporotic fractures are defined as fragility or low-trauma fractures, which occur from falling from standing height or less.2 50% of those with 1 fracture will have another. The risk and cost of osteoporotic fractures is greater than the cumulative risks of strokes, myocardial infarction, and breast cancer combined.3 The cost of all major osteoporotic fractures in the United States is expected to be greater than $18 billion by 2025.3 Osteoporosis is defined by the International Osteoporosis Foundation as a porous bone disease “in which the density and quality of bone are reduced.”4 Osteoporosis is more prevalent in women who are postmenopausal due to the retraction of estrogen, which is protective for bone health. With the silent progression, often the first indication of the disease is a fragility fracture. With the current aging baby boomer population, the United States alone has the expectation of 1.2 billion women who are postmenopausal with osteoporosis by 2030.5 The current guidelines by the US Preventive Services Task Force,7 the International Osteoporosis Foundation,4 and the National Osteoporosis Foundation,6 state that all women over age 65 should be screened, as well as high-risk women under age 65, which includes any condition that weakens bone and affects balance.4 Fixed risks, such as a previous fracture, hysterectomy, long-term glucocorticoid use, rheumatoid arthritis, or a family history of osteoporosis, put the younger woman who is menopausal at higher risk.4 Despite these recommendations, use of bone mineral density (BMD) testing for appropriate women remains low.8 One study cited rates as low as 27% of applicable women are being screened.9 The purpose of this https://doi.org/10.1016/j.nurpra.2019.02.014 1555-4155/© 2019 Elsevier Inc. All rights reserved.
article is to provide guidance for screening recommendations, for all women over age 50, with a review of risk factors, treatment modalities, and management for this at-risk population. Burden of Osteoporosis Osteoporosis affects 16% of women (about 8.6 million individuals) and 4% of men (1.6 million), with 1.5 million fragility fractures per year.10 Due to the increasing numbers of fragility fractures in an aging population, future costs will overwhelm the health care system. Increased screening and early treatment to avoid these costly and life-altering fragility fractures would help to address the current health care system’s diminishing resources. Despite the knowledge that prevention of progression from osteopenia to osteoporosis reduces morbidity and mortality, osteoporosis medication initiation rates have declined from 9.8% (95% confidence interval, 9.0%e10.6%) in 2004 to 3.3% (95% confidence interval, 2.9%e3.8%) in 2015.11 The sense of urgency to reduce the severe burden of this silent disease process on a vulnerable population cannot be understated. One recent study10 found that up to one-third of patients required hospitalization after a fragility fracture, which included a mortality rate exceeding 20% in the first year, with the preponderance of patients being female. Eighty percent of women who suffered a fragility fracture, were unable to carry out at least 1 independent activity of daily living, with 40% unable to walk independently.3 A 2018 study12 found that in the years 2002e2015, hip fractures were much higher than projected, as much as 11,000 more than necessary. Between 2002 and 2012, a decline of hip fractures was noted with the advent of new technology and treatment modalities. Since
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2012, hip fracture rates have risen, with higher rates of fracture occurring, as the proportion of women undergoing dual-energy X-ray absorptiometry (DEXA) testing has declined.12 Not enough is known regarding osteoporosis in the younger postmenopausal woman. The US Preventive Services Task Force guidelines give a “B” rating to screening the woman under age 65 and only if she is at high risk. What determines high risk is left up to the practitioner but can be guided by the fixed and nonmodifiable risks (Table 1). Pathophysiology of Osteoporosis and the Role of Genetics Bone is a living tissue and is constantly changing. The osteocytes or bone cells are of two types: Osteoclasts are bone cells that resorb or dissolve bone and osteoblasts are cells that form bone. Density of bone reaches its peak in a woman in her late 20s. Remodeling of bone occurs as one ages. Cells start to dissolve (the process of resorption), while new bone cells deposit osteoid (the process of formation).4 Bones must remain light and yet strong to absorb stress from high-impact exercise. Long bones are tubular, with a strong cortical layer, surrounding a softer, spongier core, trabecular bone.4 Osteoporosis occurs when over time, bone loss exceeds new bone growth, which leads to a restructuring of bone, that is not as strong. Hormones have a great effect on bone formation. Estrogen, parathyroid hormone, and testosterone are all important to develop and maintain bone. Estrogen is thought to have the greater impact on bone cells. Estrogen receptors are located on the cell surface of osteoblasts and are allowed into the nucleus of the cell, where it is thought that specific genes are activated.13 Prostaglandins also stimulate resorption and formation of bone, particularly with exercise-induced bone formation.14 With the withdrawal of estrogen after menopause, bone is resorbed at higher rates than it is formed. Bones lose density, despite thickening of the bone, and become more porous and brittle, predisposing the patient to fracture. Genetics can play a significant role in the development of osteoporosis. There can be subtle differences in the genetic code that activate one person’s osteoblasts or osteoclasts more than others. Regulatory mechanisms are being studied to determine this etiology, which is as yet unknown.4 Race and Ethnicity Skeletal fragility with resultant predisposition to fracture can occur in any race, ethnicity, gender, or age, but is more prevalent in postmenopausal, thin, Caucasian women.15-18 This concern is not solely an American phenomenon. In developed regions where screening is offered, countries grapple with the methodology of how to screen their high-risk populations. Prevalence rates of osteoporosis in Taiwanese adult women are 11.4%.19 Norwegian and British women have a 50% lifetime risk of osteoporosis.16,20
Table 1 Fixed and Modifiable Risk Factors Fixed Risks
Modifiable Risks
Age Female gender Family history of osteoporosis Previous fracture Ethnicity Menopause/hysterectomy Long term glucocorticoid therapy Rheumatoid arthritis
Alcohol Smoking Low body mass index Poor Nutrition Vitamin D deficiency Eating disorders Insufficient exercise Low dietary calcium intake Frequent falls
From the International Osteoporosis Foundation.4
Findings are similar among both Caucasian samples15-18 as well as in non-Hispanic Asian and Asian populations.21 Researchers retrospectively reviewed 206 charts of Korean women who presented to the emergency department with lowenergy distal radius fractures and found that those aged 50e59, had statistically significantly lower femur BMD measures compared with healthy control groups, P < 0.001.22 Younger women who were postmenopausal (ages 50e59) with distal radius fractures had low BMD values and needed to be evaluated for osteoporosis to prevent other fractures, such as those of hip and spine.22 African American women, while having higher bone density scores, were equally likely to have bone fractures as their Caucasian counterparts.23 Thus, osteoporosis affects all women from all ethnic groups, with this highest preponderance being that of Caucasian women.
Risk Factors Risk factors for osteoporosis may be either fixed or modifiable.4 A systematic review was conducted from 6 databases, demonstrating that only low body weight in a healthy population of Caucasian women, aged 40e60, was an important demographic that predicted potential future fracture and should be used for screening in high-risk populations.18 Good or fair evidence was shown that alcohol, caffeine, and reproductive history were not risk factors. A more recent study24 found that earlier screening was recommended for early menopause (<45 years old), low body weight, and family history of osteoporosis. The greatest risk for the development of osteoporosis is low body weight and early menopause, which accelerate bone loss.18 Research has shown that intake of calcium, physical activity, smoking, age of menarche, amenorrhea history, or family history of osteoporosis, race, and current age had inconsistent evidence for osteoporosis.18 Although these factors do not increase risk, consumption of hormonal birth control methods have been shown to reduce bone density. After 2 years of depot medroxyprogesterone use, a 5.7%e6.8% loss of bone mineral density of the spine and 3.6%e5.8% at the hip was found.25 Even low-dose estrogen, combination oral contraceptives, were shown to reduce bone density, albeit by a much smaller percentage than depot medroxyprogesterone. Unfortunately, even after discontinuing hormonal birth control methods, not all bone density was restored to precontraceptive levels.25 Skeletal fragility has the potential to affect not only the physical but also the psychological component. Both depression and anxiety have been shown to coexist with osteoporosis.26 These are chronic conditions that can affect appetite, energy level, attitude, and cognition.27 Osteoporosis characteristics were found to be activity limiting and life altering when increased probability of fragility fractures was considered. The perceived or real loss of independence was likely a correlate of the more recent relationship of anxiety and a higher propensity for fracture risk.28 A mindebody connection exists, demonstrating the impact that the 2 spheres have with one another. In the 2018 study, those with lower anxiety levels had a 10-year fracture risk of 20%, whereas those with higher anxiety levels had a 25% risk for fracture.28 Fragility fractures have also been studied with regard to their impairment to patient’s mental health in terms of depression.26 This newer finding demonstrated the linkage of anxiety with fragility in the postmenopausal woman. When questioning study participants on levels of anxiety, concepts such as tension, fear, and restlessness were assessed.28 These attributes directly linked to the concept of fragility, when one considers the emotional disquiet that accompanies the thought of being fragile and the cautiousness that occurs from the fear of acquiring a fragility fracture.
K.D. French, D. Emanuele / The Journal for Nurse Practitioners 15 (2019) 347e350
Screening and Diagnosis of Osteoporosis Because of the silent nature of the disease, providers should not wait until a woman is older than 65 to start screening for osteoporosis. If a younger postmenopausal woman has characteristics that put her at higher risk, such as low body weight, Caucasian or Asian race, a history of premature menopause, a chronic autoimmune disease, or if they have had long-term steroid use, they should be screened earlier. Identifying high-risk women individually is important so that tailored care can be given, with the ultimate goal of avoiding the first fragility fracture. All women who are postmenopausal should be annually screened for osteoporosis with a validated risk assessment tool. The FRAX is a web-based calculator that assesses the 10-year risk of osteoporotic fractures based on individual risk factors, with or without BMD values.4 The tool is freely available either for desktop or mobile applications. If the score is > 20% for a major osteoporotic fracture or 3% for a hip fracture, she should be advised on next steps to prevent a pathologic fracture after obtaining a DEXA scan. Evaluation of Osteoporosis With Imaging Currently in the United States, the DEXA scan is the gold standard for testing BMD. DEXA bone densitometry is currently the best standardized method available not only to diagnose osteoporosis but to estimate fracture risk accurately.4,6,29 The DEXA scan measures spine and hip bone density with low doses of radiation, the equivalent to less than one-tenth of a standard chest x-ray, and less than exposure to a day’s natural radiation.29 The hip density is used for treatment determination. Follow-up DEXA scans should be performed at the same facility and with the same machine if possible, as measurements obtained with different DEXA equipment cannot be directly compared.29 Calcaneal ultrasound has also been used to screen women and its use is more prevalent in other countries. With large numbers of women who will need screening in the future, this is a possible alternative to the use of DEXA scanning, which requires more expensive equipment. However, peripheral testing, such as a calcaneal ultrasound, may predict risk for fracture of spine or hip, but not as helpful with indicating response to medical therapy.29 The evaluation and treatment of osteoporosis is a function of primary care. Far too many patients require screening and treatment to defer their care to endocrinologists or rheumatologists. Specialists should be used for high-risk patients who present with osteoporosis that is not age related or due to an underlying pathology. Consideration of individual patients’ needs and circumstances is necessary when interpreting the DEXA results to determine specific treatment. The DEXA results are derived from bone density results of young adults (referred to as a T-score). Osteoporosis is diagnosed if the patient’s BMD is equal to or more than 2.5 standard deviations below this reference (Table 2).4 Management of Osteoporosis Prevention of bone loss is the first step in management of this disease. Optimal bone growth occurs in youth, with the peak bone Table 2 Dual-Energy X-ray Absorptiometry (DEXA) Screening Values Bone Density Status
Hip Bone Mineral Density
Normal Osteopenia Osteoporosis Severe osteoporosis
T-score of e1 or above T-score lower than e1 and greater than e2.5 T-score of e2.5 or lower T-score of e2.5 or lower, and presence of at least 1 fragility fracture
From the International Osteoporosis Foundation.4
349
mass achieved in the mid-20s.4 A 10% increase in bone mass in children reduces the risk of an osteoporotic fracture during adulthood by 50%.4 In addition to the role of genetics, environmental factors have an enormous impact on bone health. A cross-sectional study on Scottish women was performed, to examine the influence of diet on the development of osteoporosis. Researchers found that a diet high in fruits and vegetables was associated with less bone resorption (r ¼ 0.081, P < 0.001).20 Likewise, dietary patterns that contained high amounts of processed foods were associated with a decrease in bone density (r ¼ e0.056, P < 0.001).20 The recommendation for vitamin D from the National Osteoporosis Foundation for those over age 50 is 800e1,000 IU of vitamin D3. Calcium is best obtained from food sources, with the recommendation for women over 50, to receive 1,200 mg from all sources daily.29 The conclusion is that healthy bones are a result of a healthier, balanced, and calcium-rich diet. Aerobic and weight-bearing exercise are both necessary, in addition to vitamin D and calcium supplementation for bone strength.24,30 Summarizing good bone health for those at higher risk, appears to come down to proper diet and exercise to prevent early osteoporosis. Conversely, behaviors such as smoking, diets high in fat and processed foods, and lack of exercise contributed to poor bone health. Lifelong exercise is an effective way to sustain bone health in all females; impact exercise and resistance training are best to preserve and improve bone health in older women. Once a diagnosis of osteoporosis has been made, treatment should begin. Adequate calcium and vitamin D levels are needed in the blood to provide the building blocks for bone. A complete metabolic panel should be obtained. If calcium levels are within normal limits and no other concerns exist for hyperparathyroidism, autoimmune disease comorbidity, cancerous pathology, or other underlying disease, treatment may be initiated. Medications are recommended dependent on the degree of bone loss that has occurred, as well as the underlying health and age of the patient. For instance, women with a history of blood clotting or exposure to radiation, should not take teriparatide or abaloparatide.6 Most commonly prescribed are the bisphosphonates, which can be given daily, weekly, or monthly. The mechanism of action is to inhibit osteoclast activity, which reduces bone resorption and turnover.31 These oral medications can be difficult to tolerate if the patient suffers from esophagitis or gastroesophageal reflux disorder or is unable to stay upright at least 1 hour after ingestion. Zoledronic acid (a bisphosphonate) is given as an infusion once yearly, which can address the issues of taking bisphosphonates orally. Raloxifene belongs to the subclass of selective estrogen receptor modulators (SERMs), which act as an estrogen agonist in bone, decreasing bone resorption and turnover. The added benefit with these drugs are that they also are estrogen antagonists in breast and uterine tissue, thereby inhibiting breast epithelium proliferation and decreasing endometrial hyperplasia risk.31 Due to the nature of this medication, there is an increase in the development of venous thromboembolism. Newer medications such as denosumab, which is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, reduces osteoclast formation, maintenance, and survival and reduces bone resorption and turnover.31 The medication is given subcutaneously every 6 months. As with all medications, insurance coverage must be considered, and often patients must fail less expensive drugs before being able to obtain injectable or infusion medications. All of the preceding medications, with the exception of zoledronic acid, can be prescribed within the parameters of primary care. Red flags Indicating Specialty Referral Women who have disorders that cause bone loss and fractures from low trauma, parathyroid disease, autoimmune diseases such
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as lupus, or take high-dose corticosteroids should be managed by either endocrinology or rheumatology. Further workup to exclude such conditions may be done by primary care, to include screening for parathyroid hormone, ionized serum calcium, and a 24-hour urine for calcium excretion. Conclusion Primary prevention of fragility fractures is the most costeffective and proactive approach to sustaining bone health. The risk of sustaining a fragility fracture increases with age due to decreases in bone BMD and the increasing risk for falls as women age. Primary prevention of osteoporotic fractures is not occurring within our health care systems. Nurse practitioners must be prepared to screen appropriate women for a disease that is often silent. Customizing the management and care for each woman is imperative to reduce long term fragility, both physically and emotionally. With increased awareness of facture risk, women will be more empowered to take care of their bone health, thus reducing morbidity and mortality. The overall well-being of women who are postmenopausal, a growing demographic of the population, should be made a high priority. References 1. Akesson K, Mitchell P. Capture the fracture: a global campaign to break the fragility fracture cycle. 2012. http://www.capture-the-fracture.org. Accessed November 15, 2018. 2. UpToDate. Osteoporotic fracture risk assessment. 2019. https://www. uptodate.com/contents/osteoporotic-fracture-risk-assessment. Accessed February 11, 2019. 3. Singer A, Exuzides A, Spangler L, et al. Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin Proc. 2015;90(1):53-62. https://doi:10. 1016/j.mayocp.2014.09.011. 4. International Osteoporosis Foundation. What is osteoporosis? 2018. https:// www.iofbonehealth.org/what-is-osteoporosis. Accessed January 4, 2019. 5. Pallagatti S, Parnam P, Sheikh S, Gupta D. Efficacy of panoramic radiography in the detection of osteoporosis in postmenopausal women when compared to dual energy x-ray absorptiometry. Open Dent J. 2017;11:1-10. 6. National Osteoporosis Foundation. Bone source: knowledge. Competence. Results. 2018. https://www.cme.nof.org/. Accessed December 28, 2018. 7. United Services Preventive Services Task Force. Draft recommendation statement: Osteoporosis to prevent fractures: Screening. 2017. https:// www.uspreventiveservicestaskforce.org/Announcements/News/Item/final recommendation-statement-screening-for-osteoporosis-to-prevent-fractures. Accessed December 15, 2018. 8. Meadows ES, Whango A, McQuarrie N, Gilra N, Mitchell BD, Mershon JL. Compliance with mammography and bone mineral density screening in women at least 50 years old. Menopause. 2011;18(7):794-801. https://doi: 10. 1097/gme.obo13e3182083f28. 9. LaValle LA, Scott MA, Hulkower SD. Challenges in the screening and management of osteoporosis. N C Med J. 2011;77(6):416-419. 10. Altkorn D, Cifu AS. Screening for osteoporosis. JAMA. 2015;313(14):1467-1468. https://doi:10.1001/jama.2015.1064. 11. Desai R, Mahseri M, Abdia Y, et al. Association of osteoporosis medication use after hip fracture with prevention of subsequent nonvertebral fractures: an instrumental variable analysis. Geriatr JAMA Network Open. 2018;1(3). https:// doi:10.1001/jamanetworkopen.2018.0826. 12. Lewicki M, Wright N, Curtis JR, et al. Hip fracture trends in the United States, 2002 to 2015. Osteo Int. 2018;29:717-722. https://doi:10.1007/ s00198017-4345-0.
13. Bonnelye E, Aubin JE. Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone. J Clin Endocrinol Metab. 2005;90:3115-3121. 14. Bonewald L. Use it or lose it to age: a review of bone and muscle communication. Bone. 2018;120:212-218. https://doi.org/10.1016/j.bone.2018.11.002. 15. Schousboe JT. Cost-effectiveness of screen and treat strategies for low bone mineral density: how do we screen, who do we screen and who do we treat? Appl Health Econ Health Policy. 2008;6(1):1-18. 16. Sosa D, Vilaplana L, Guerri R, et al. Are the hip fracture rates among Norwegian women explained by impaired bone material properties? J Bone Miner Metab. 2015;30(10):1784-1789. https://doi:10.1002/jbmr.2537. 17. Tan BK, Price RI, Briffa NK, Dhaliwal SS, DayR E, Singer KP. Assessment of osteoporotic fracture risk community settings: a study of post-menopausal women in Australia. Health Soc Care Commun. 2008;16(6):621-628. https:// doi:10.1111/j.1365 2524.2008.00786.x. 18. Waugh EJ, Lam MA, Hawker GA, et al. Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature. Osteoporos Int. 2009;20(1):1-21. https://doi:10.1007/s00198-0080643-x. 19. Lee NY, Lam SC, Kwan T, Ting Yan BN, Yin JCL, Yin AC. Preliminary investigation on prevalence of osteoporosis and osteopenia: should we tune our focus on healthy adults? Jpn J Nurs Sci. 2015;12(3):232-248. https://doi:10. 1111/jjns.12063. 20. Hardcastle AC, Aucott L, Fraser WD, Reid DM, Macdonald HM. Dietary patterns, bone resorption, and bone mineral density in early post-menopausal Scottish women. Eur J Clin Nutr. 2011;65(3):378-385. https://doi:10.1038/ejcn.2010. 264. 21. Cosman F, Krege JH, Looker AC, et al. Spine fracture prevalence in a nationally representative sample of US women and men aged 40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013e2014. Osteoporo Int. 2017;28(6):1857-1866. https://doi:10.1007/s00198-017-39489. 22. Jung HJ, Park HY, Kim JS, Yoon JO, Jeon IH. Bone mineral density and prevalence of osteoporosis in postmenopausal Korean women with low-energy distal radius fractures. J Korean Med Sci. 2016;31(6):972-975. https://doi.org/ 10.3346/jkms.2016.31.6.972. 23. Aggarwal L, Masuda C. Osteoporosis: a quick update. J Fam Pract. 2018;67(2): 59-62. 24. Watts NB, Manson JE. Osteoporosis and fracture risk evaluation and management: shared decision making in clinical practice. JAMA. 2017;317(3): 253-254. https://doi:10.1001/jama.2016.19087. 25. Berenson AB, Rahman M, Breitkopf CR, Bi LX. Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives on bone mineral density. Obstet Gynecol. 2008;112(4):788-800. 26. Erez HB, Weller A, Vaisman N, Kreitler S. The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporosis. 2012;7:247-255. https://doi:10.1007/s11657-012-0105-0. 27. Lee CW, Liao C, Lin C, Liang J, Sung F, Kao C. Original article: increased risk of osteoporosis in patients with depression. A population-based retrospective cohort study. Mayo Clin Proc. 2015;90:63-70. https://doi:10.1016/j.mayocp. 2014.11.009. 28. Rapaport L. Anxiety tied to fracture risk in postmenopausal women. Medscape. June 13, 2018. Reuters Health Information. https://www.medscape.com/ viewarticle/898071?src¼wnl_edit_tpal&uac¼173059HR&ipD¼1659044&faf¼1. Accessed December 1, 2018. 29. RadiologyInfo.org. Bone densitometry. 2018. https://www.radiologyinfo.org/ en/info.cfm?pg¼dexa. Accessed December 28, 2018. 30. Centers for Disease Control and Prevention. Physical activity. 2018. https:// www.cdc.gov/physicalactivity/basics/index.html?CDC_AA_refVal¼https%3A%2 2Fwww.cdc.gov%2Fphysicalactivity%2Fbasics%2Fmeasuring%2Findex.html. Accessed January 4, 2019. 31. Epocrates. Osteoporosis. 2018. https://online.epocrates.com/. Accessed December 30, 2018.
Karen D. French, MSN, FNP-C, is an assistant professor at Azusa Pacific University, Azusa, CA, and can be contacted at [email protected]. Donna Emanuele, DNP, FANPBC, FAANP, is an associate professor and director of the DNP program, Western University of Health Sciences, College of Graduate Nursing, Pomona, CA. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.
Contents lists available at ScienceDirect
The Journal for Nurse Practitioners journal homepage: www.npjournal.org
Osteoporosis: Increasing Screening and Treatment for Postmenopausal Women Karen D. French, MSN, FNP-C, Donna Emanuele, DNP, FNP-BC a b s t r a c t Keywords: bone mineral density fracture fragility osteoporosis postmenopausal
Postmenopausal women are at risk for osteoporosis, a skeletal loss of integrity, which predisposes them to increased fall rates and both primary and secondary skeletal fractures. The risk and cost of osteoporotic fractures is greater than the risks of strokes, myocardial infarction, and breast cancer combined. With the baby boomer population reaching postmenopausal ages, the burden of care and cost will likely become prohibitive if the current rates of screening and treatment continue. Nurse practitioners are at the forefront of the primary prevention of osteoporotic fractures, in addition to having the skill and education to manage the osteoporotic patient. © 2019 Elsevier Inc. All rights reserved.
Physical skeletal loss of integrity predisposes women to increased fall rates, with resultant skeletal fractures. Every 3 seconds, someone suffers an osteoporotic fracture.1 Osteoporotic fractures are defined as fragility or low-trauma fractures, which occur from falling from standing height or less.2 50% of those with 1 fracture will have another. The risk and cost of osteoporotic fractures is greater than the cumulative risks of strokes, myocardial infarction, and breast cancer combined.3 The cost of all major osteoporotic fractures in the United States is expected to be greater than $18 billion by 2025.3 Osteoporosis is defined by the International Osteoporosis Foundation as a porous bone disease “in which the density and quality of bone are reduced.”4 Osteoporosis is more prevalent in women who are postmenopausal due to the retraction of estrogen, which is protective for bone health. With the silent progression, often the first indication of the disease is a fragility fracture. With the current aging baby boomer population, the United States alone has the expectation of 1.2 billion women who are postmenopausal with osteoporosis by 2030.5 The current guidelines by the US Preventive Services Task Force,7 the International Osteoporosis Foundation,4 and the National Osteoporosis Foundation,6 state that all women over age 65 should be screened, as well as high-risk women under age 65, which includes any condition that weakens bone and affects balance.4 Fixed risks, such as a previous fracture, hysterectomy, long-term glucocorticoid use, rheumatoid arthritis, or a family history of osteoporosis, put the younger woman who is menopausal at higher risk.4 Despite these recommendations, use of bone mineral density (BMD) testing for appropriate women remains low.8 One study cited rates as low as 27% of applicable women are being screened.9 The purpose of this https://doi.org/10.1016/j.nurpra.2019.02.014 1555-4155/© 2019 Elsevier Inc. All rights reserved.
article is to provide guidance for screening recommendations, for all women over age 50, with a review of risk factors, treatment modalities, and management for this at-risk population. Burden of Osteoporosis Osteoporosis affects 16% of women (about 8.6 million individuals) and 4% of men (1.6 million), with 1.5 million fragility fractures per year.10 Due to the increasing numbers of fragility fractures in an aging population, future costs will overwhelm the health care system. Increased screening and early treatment to avoid these costly and life-altering fragility fractures would help to address the current health care system’s diminishing resources. Despite the knowledge that prevention of progression from osteopenia to osteoporosis reduces morbidity and mortality, osteoporosis medication initiation rates have declined from 9.8% (95% confidence interval, 9.0%e10.6%) in 2004 to 3.3% (95% confidence interval, 2.9%e3.8%) in 2015.11 The sense of urgency to reduce the severe burden of this silent disease process on a vulnerable population cannot be understated. One recent study10 found that up to one-third of patients required hospitalization after a fragility fracture, which included a mortality rate exceeding 20% in the first year, with the preponderance of patients being female. Eighty percent of women who suffered a fragility fracture, were unable to carry out at least 1 independent activity of daily living, with 40% unable to walk independently.3 A 2018 study12 found that in the years 2002e2015, hip fractures were much higher than projected, as much as 11,000 more than necessary. Between 2002 and 2012, a decline of hip fractures was noted with the advent of new technology and treatment modalities. Since
348
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2012, hip fracture rates have risen, with higher rates of fracture occurring, as the proportion of women undergoing dual-energy X-ray absorptiometry (DEXA) testing has declined.12 Not enough is known regarding osteoporosis in the younger postmenopausal woman. The US Preventive Services Task Force guidelines give a “B” rating to screening the woman under age 65 and only if she is at high risk. What determines high risk is left up to the practitioner but can be guided by the fixed and nonmodifiable risks (Table 1). Pathophysiology of Osteoporosis and the Role of Genetics Bone is a living tissue and is constantly changing. The osteocytes or bone cells are of two types: Osteoclasts are bone cells that resorb or dissolve bone and osteoblasts are cells that form bone. Density of bone reaches its peak in a woman in her late 20s. Remodeling of bone occurs as one ages. Cells start to dissolve (the process of resorption), while new bone cells deposit osteoid (the process of formation).4 Bones must remain light and yet strong to absorb stress from high-impact exercise. Long bones are tubular, with a strong cortical layer, surrounding a softer, spongier core, trabecular bone.4 Osteoporosis occurs when over time, bone loss exceeds new bone growth, which leads to a restructuring of bone, that is not as strong. Hormones have a great effect on bone formation. Estrogen, parathyroid hormone, and testosterone are all important to develop and maintain bone. Estrogen is thought to have the greater impact on bone cells. Estrogen receptors are located on the cell surface of osteoblasts and are allowed into the nucleus of the cell, where it is thought that specific genes are activated.13 Prostaglandins also stimulate resorption and formation of bone, particularly with exercise-induced bone formation.14 With the withdrawal of estrogen after menopause, bone is resorbed at higher rates than it is formed. Bones lose density, despite thickening of the bone, and become more porous and brittle, predisposing the patient to fracture. Genetics can play a significant role in the development of osteoporosis. There can be subtle differences in the genetic code that activate one person’s osteoblasts or osteoclasts more than others. Regulatory mechanisms are being studied to determine this etiology, which is as yet unknown.4 Race and Ethnicity Skeletal fragility with resultant predisposition to fracture can occur in any race, ethnicity, gender, or age, but is more prevalent in postmenopausal, thin, Caucasian women.15-18 This concern is not solely an American phenomenon. In developed regions where screening is offered, countries grapple with the methodology of how to screen their high-risk populations. Prevalence rates of osteoporosis in Taiwanese adult women are 11.4%.19 Norwegian and British women have a 50% lifetime risk of osteoporosis.16,20
Table 1 Fixed and Modifiable Risk Factors Fixed Risks
Modifiable Risks
Age Female gender Family history of osteoporosis Previous fracture Ethnicity Menopause/hysterectomy Long term glucocorticoid therapy Rheumatoid arthritis
Alcohol Smoking Low body mass index Poor Nutrition Vitamin D deficiency Eating disorders Insufficient exercise Low dietary calcium intake Frequent falls
From the International Osteoporosis Foundation.4
Findings are similar among both Caucasian samples15-18 as well as in non-Hispanic Asian and Asian populations.21 Researchers retrospectively reviewed 206 charts of Korean women who presented to the emergency department with lowenergy distal radius fractures and found that those aged 50e59, had statistically significantly lower femur BMD measures compared with healthy control groups, P < 0.001.22 Younger women who were postmenopausal (ages 50e59) with distal radius fractures had low BMD values and needed to be evaluated for osteoporosis to prevent other fractures, such as those of hip and spine.22 African American women, while having higher bone density scores, were equally likely to have bone fractures as their Caucasian counterparts.23 Thus, osteoporosis affects all women from all ethnic groups, with this highest preponderance being that of Caucasian women.
Risk Factors Risk factors for osteoporosis may be either fixed or modifiable.4 A systematic review was conducted from 6 databases, demonstrating that only low body weight in a healthy population of Caucasian women, aged 40e60, was an important demographic that predicted potential future fracture and should be used for screening in high-risk populations.18 Good or fair evidence was shown that alcohol, caffeine, and reproductive history were not risk factors. A more recent study24 found that earlier screening was recommended for early menopause (<45 years old), low body weight, and family history of osteoporosis. The greatest risk for the development of osteoporosis is low body weight and early menopause, which accelerate bone loss.18 Research has shown that intake of calcium, physical activity, smoking, age of menarche, amenorrhea history, or family history of osteoporosis, race, and current age had inconsistent evidence for osteoporosis.18 Although these factors do not increase risk, consumption of hormonal birth control methods have been shown to reduce bone density. After 2 years of depot medroxyprogesterone use, a 5.7%e6.8% loss of bone mineral density of the spine and 3.6%e5.8% at the hip was found.25 Even low-dose estrogen, combination oral contraceptives, were shown to reduce bone density, albeit by a much smaller percentage than depot medroxyprogesterone. Unfortunately, even after discontinuing hormonal birth control methods, not all bone density was restored to precontraceptive levels.25 Skeletal fragility has the potential to affect not only the physical but also the psychological component. Both depression and anxiety have been shown to coexist with osteoporosis.26 These are chronic conditions that can affect appetite, energy level, attitude, and cognition.27 Osteoporosis characteristics were found to be activity limiting and life altering when increased probability of fragility fractures was considered. The perceived or real loss of independence was likely a correlate of the more recent relationship of anxiety and a higher propensity for fracture risk.28 A mindebody connection exists, demonstrating the impact that the 2 spheres have with one another. In the 2018 study, those with lower anxiety levels had a 10-year fracture risk of 20%, whereas those with higher anxiety levels had a 25% risk for fracture.28 Fragility fractures have also been studied with regard to their impairment to patient’s mental health in terms of depression.26 This newer finding demonstrated the linkage of anxiety with fragility in the postmenopausal woman. When questioning study participants on levels of anxiety, concepts such as tension, fear, and restlessness were assessed.28 These attributes directly linked to the concept of fragility, when one considers the emotional disquiet that accompanies the thought of being fragile and the cautiousness that occurs from the fear of acquiring a fragility fracture.
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Screening and Diagnosis of Osteoporosis Because of the silent nature of the disease, providers should not wait until a woman is older than 65 to start screening for osteoporosis. If a younger postmenopausal woman has characteristics that put her at higher risk, such as low body weight, Caucasian or Asian race, a history of premature menopause, a chronic autoimmune disease, or if they have had long-term steroid use, they should be screened earlier. Identifying high-risk women individually is important so that tailored care can be given, with the ultimate goal of avoiding the first fragility fracture. All women who are postmenopausal should be annually screened for osteoporosis with a validated risk assessment tool. The FRAX is a web-based calculator that assesses the 10-year risk of osteoporotic fractures based on individual risk factors, with or without BMD values.4 The tool is freely available either for desktop or mobile applications. If the score is > 20% for a major osteoporotic fracture or 3% for a hip fracture, she should be advised on next steps to prevent a pathologic fracture after obtaining a DEXA scan. Evaluation of Osteoporosis With Imaging Currently in the United States, the DEXA scan is the gold standard for testing BMD. DEXA bone densitometry is currently the best standardized method available not only to diagnose osteoporosis but to estimate fracture risk accurately.4,6,29 The DEXA scan measures spine and hip bone density with low doses of radiation, the equivalent to less than one-tenth of a standard chest x-ray, and less than exposure to a day’s natural radiation.29 The hip density is used for treatment determination. Follow-up DEXA scans should be performed at the same facility and with the same machine if possible, as measurements obtained with different DEXA equipment cannot be directly compared.29 Calcaneal ultrasound has also been used to screen women and its use is more prevalent in other countries. With large numbers of women who will need screening in the future, this is a possible alternative to the use of DEXA scanning, which requires more expensive equipment. However, peripheral testing, such as a calcaneal ultrasound, may predict risk for fracture of spine or hip, but not as helpful with indicating response to medical therapy.29 The evaluation and treatment of osteoporosis is a function of primary care. Far too many patients require screening and treatment to defer their care to endocrinologists or rheumatologists. Specialists should be used for high-risk patients who present with osteoporosis that is not age related or due to an underlying pathology. Consideration of individual patients’ needs and circumstances is necessary when interpreting the DEXA results to determine specific treatment. The DEXA results are derived from bone density results of young adults (referred to as a T-score). Osteoporosis is diagnosed if the patient’s BMD is equal to or more than 2.5 standard deviations below this reference (Table 2).4 Management of Osteoporosis Prevention of bone loss is the first step in management of this disease. Optimal bone growth occurs in youth, with the peak bone Table 2 Dual-Energy X-ray Absorptiometry (DEXA) Screening Values Bone Density Status
Hip Bone Mineral Density
Normal Osteopenia Osteoporosis Severe osteoporosis
T-score of e1 or above T-score lower than e1 and greater than e2.5 T-score of e2.5 or lower T-score of e2.5 or lower, and presence of at least 1 fragility fracture
From the International Osteoporosis Foundation.4
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mass achieved in the mid-20s.4 A 10% increase in bone mass in children reduces the risk of an osteoporotic fracture during adulthood by 50%.4 In addition to the role of genetics, environmental factors have an enormous impact on bone health. A cross-sectional study on Scottish women was performed, to examine the influence of diet on the development of osteoporosis. Researchers found that a diet high in fruits and vegetables was associated with less bone resorption (r ¼ 0.081, P < 0.001).20 Likewise, dietary patterns that contained high amounts of processed foods were associated with a decrease in bone density (r ¼ e0.056, P < 0.001).20 The recommendation for vitamin D from the National Osteoporosis Foundation for those over age 50 is 800e1,000 IU of vitamin D3. Calcium is best obtained from food sources, with the recommendation for women over 50, to receive 1,200 mg from all sources daily.29 The conclusion is that healthy bones are a result of a healthier, balanced, and calcium-rich diet. Aerobic and weight-bearing exercise are both necessary, in addition to vitamin D and calcium supplementation for bone strength.24,30 Summarizing good bone health for those at higher risk, appears to come down to proper diet and exercise to prevent early osteoporosis. Conversely, behaviors such as smoking, diets high in fat and processed foods, and lack of exercise contributed to poor bone health. Lifelong exercise is an effective way to sustain bone health in all females; impact exercise and resistance training are best to preserve and improve bone health in older women. Once a diagnosis of osteoporosis has been made, treatment should begin. Adequate calcium and vitamin D levels are needed in the blood to provide the building blocks for bone. A complete metabolic panel should be obtained. If calcium levels are within normal limits and no other concerns exist for hyperparathyroidism, autoimmune disease comorbidity, cancerous pathology, or other underlying disease, treatment may be initiated. Medications are recommended dependent on the degree of bone loss that has occurred, as well as the underlying health and age of the patient. For instance, women with a history of blood clotting or exposure to radiation, should not take teriparatide or abaloparatide.6 Most commonly prescribed are the bisphosphonates, which can be given daily, weekly, or monthly. The mechanism of action is to inhibit osteoclast activity, which reduces bone resorption and turnover.31 These oral medications can be difficult to tolerate if the patient suffers from esophagitis or gastroesophageal reflux disorder or is unable to stay upright at least 1 hour after ingestion. Zoledronic acid (a bisphosphonate) is given as an infusion once yearly, which can address the issues of taking bisphosphonates orally. Raloxifene belongs to the subclass of selective estrogen receptor modulators (SERMs), which act as an estrogen agonist in bone, decreasing bone resorption and turnover. The added benefit with these drugs are that they also are estrogen antagonists in breast and uterine tissue, thereby inhibiting breast epithelium proliferation and decreasing endometrial hyperplasia risk.31 Due to the nature of this medication, there is an increase in the development of venous thromboembolism. Newer medications such as denosumab, which is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, reduces osteoclast formation, maintenance, and survival and reduces bone resorption and turnover.31 The medication is given subcutaneously every 6 months. As with all medications, insurance coverage must be considered, and often patients must fail less expensive drugs before being able to obtain injectable or infusion medications. All of the preceding medications, with the exception of zoledronic acid, can be prescribed within the parameters of primary care. Red flags Indicating Specialty Referral Women who have disorders that cause bone loss and fractures from low trauma, parathyroid disease, autoimmune diseases such
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as lupus, or take high-dose corticosteroids should be managed by either endocrinology or rheumatology. Further workup to exclude such conditions may be done by primary care, to include screening for parathyroid hormone, ionized serum calcium, and a 24-hour urine for calcium excretion. Conclusion Primary prevention of fragility fractures is the most costeffective and proactive approach to sustaining bone health. The risk of sustaining a fragility fracture increases with age due to decreases in bone BMD and the increasing risk for falls as women age. Primary prevention of osteoporotic fractures is not occurring within our health care systems. Nurse practitioners must be prepared to screen appropriate women for a disease that is often silent. Customizing the management and care for each woman is imperative to reduce long term fragility, both physically and emotionally. With increased awareness of facture risk, women will be more empowered to take care of their bone health, thus reducing morbidity and mortality. The overall well-being of women who are postmenopausal, a growing demographic of the population, should be made a high priority. References 1. Akesson K, Mitchell P. Capture the fracture: a global campaign to break the fragility fracture cycle. 2012. http://www.capture-the-fracture.org. Accessed November 15, 2018. 2. UpToDate. Osteoporotic fracture risk assessment. 2019. https://www. uptodate.com/contents/osteoporotic-fracture-risk-assessment. Accessed February 11, 2019. 3. Singer A, Exuzides A, Spangler L, et al. Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin Proc. 2015;90(1):53-62. https://doi:10. 1016/j.mayocp.2014.09.011. 4. International Osteoporosis Foundation. What is osteoporosis? 2018. https:// www.iofbonehealth.org/what-is-osteoporosis. Accessed January 4, 2019. 5. Pallagatti S, Parnam P, Sheikh S, Gupta D. Efficacy of panoramic radiography in the detection of osteoporosis in postmenopausal women when compared to dual energy x-ray absorptiometry. Open Dent J. 2017;11:1-10. 6. National Osteoporosis Foundation. Bone source: knowledge. Competence. Results. 2018. https://www.cme.nof.org/. Accessed December 28, 2018. 7. United Services Preventive Services Task Force. Draft recommendation statement: Osteoporosis to prevent fractures: Screening. 2017. https:// www.uspreventiveservicestaskforce.org/Announcements/News/Item/final recommendation-statement-screening-for-osteoporosis-to-prevent-fractures. Accessed December 15, 2018. 8. Meadows ES, Whango A, McQuarrie N, Gilra N, Mitchell BD, Mershon JL. Compliance with mammography and bone mineral density screening in women at least 50 years old. Menopause. 2011;18(7):794-801. https://doi: 10. 1097/gme.obo13e3182083f28. 9. LaValle LA, Scott MA, Hulkower SD. Challenges in the screening and management of osteoporosis. N C Med J. 2011;77(6):416-419. 10. Altkorn D, Cifu AS. Screening for osteoporosis. JAMA. 2015;313(14):1467-1468. https://doi:10.1001/jama.2015.1064. 11. Desai R, Mahseri M, Abdia Y, et al. Association of osteoporosis medication use after hip fracture with prevention of subsequent nonvertebral fractures: an instrumental variable analysis. Geriatr JAMA Network Open. 2018;1(3). https:// doi:10.1001/jamanetworkopen.2018.0826. 12. Lewicki M, Wright N, Curtis JR, et al. Hip fracture trends in the United States, 2002 to 2015. Osteo Int. 2018;29:717-722. https://doi:10.1007/ s00198017-4345-0.
13. Bonnelye E, Aubin JE. Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone. J Clin Endocrinol Metab. 2005;90:3115-3121. 14. Bonewald L. Use it or lose it to age: a review of bone and muscle communication. Bone. 2018;120:212-218. https://doi.org/10.1016/j.bone.2018.11.002. 15. Schousboe JT. Cost-effectiveness of screen and treat strategies for low bone mineral density: how do we screen, who do we screen and who do we treat? Appl Health Econ Health Policy. 2008;6(1):1-18. 16. Sosa D, Vilaplana L, Guerri R, et al. Are the hip fracture rates among Norwegian women explained by impaired bone material properties? J Bone Miner Metab. 2015;30(10):1784-1789. https://doi:10.1002/jbmr.2537. 17. Tan BK, Price RI, Briffa NK, Dhaliwal SS, DayR E, Singer KP. Assessment of osteoporotic fracture risk community settings: a study of post-menopausal women in Australia. Health Soc Care Commun. 2008;16(6):621-628. https:// doi:10.1111/j.1365 2524.2008.00786.x. 18. Waugh EJ, Lam MA, Hawker GA, et al. Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature. Osteoporos Int. 2009;20(1):1-21. https://doi:10.1007/s00198-0080643-x. 19. Lee NY, Lam SC, Kwan T, Ting Yan BN, Yin JCL, Yin AC. Preliminary investigation on prevalence of osteoporosis and osteopenia: should we tune our focus on healthy adults? Jpn J Nurs Sci. 2015;12(3):232-248. https://doi:10. 1111/jjns.12063. 20. Hardcastle AC, Aucott L, Fraser WD, Reid DM, Macdonald HM. Dietary patterns, bone resorption, and bone mineral density in early post-menopausal Scottish women. Eur J Clin Nutr. 2011;65(3):378-385. https://doi:10.1038/ejcn.2010. 264. 21. Cosman F, Krege JH, Looker AC, et al. Spine fracture prevalence in a nationally representative sample of US women and men aged 40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013e2014. Osteoporo Int. 2017;28(6):1857-1866. https://doi:10.1007/s00198-017-39489. 22. Jung HJ, Park HY, Kim JS, Yoon JO, Jeon IH. Bone mineral density and prevalence of osteoporosis in postmenopausal Korean women with low-energy distal radius fractures. J Korean Med Sci. 2016;31(6):972-975. https://doi.org/ 10.3346/jkms.2016.31.6.972. 23. Aggarwal L, Masuda C. Osteoporosis: a quick update. J Fam Pract. 2018;67(2): 59-62. 24. Watts NB, Manson JE. Osteoporosis and fracture risk evaluation and management: shared decision making in clinical practice. JAMA. 2017;317(3): 253-254. https://doi:10.1001/jama.2016.19087. 25. Berenson AB, Rahman M, Breitkopf CR, Bi LX. Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives on bone mineral density. Obstet Gynecol. 2008;112(4):788-800. 26. Erez HB, Weller A, Vaisman N, Kreitler S. The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporosis. 2012;7:247-255. https://doi:10.1007/s11657-012-0105-0. 27. Lee CW, Liao C, Lin C, Liang J, Sung F, Kao C. Original article: increased risk of osteoporosis in patients with depression. A population-based retrospective cohort study. Mayo Clin Proc. 2015;90:63-70. https://doi:10.1016/j.mayocp. 2014.11.009. 28. Rapaport L. Anxiety tied to fracture risk in postmenopausal women. Medscape. June 13, 2018. Reuters Health Information. https://www.medscape.com/ viewarticle/898071?src¼wnl_edit_tpal&uac¼173059HR&ipD¼1659044&faf¼1. Accessed December 1, 2018. 29. RadiologyInfo.org. Bone densitometry. 2018. https://www.radiologyinfo.org/ en/info.cfm?pg¼dexa. Accessed December 28, 2018. 30. Centers for Disease Control and Prevention. Physical activity. 2018. https:// www.cdc.gov/physicalactivity/basics/index.html?CDC_AA_refVal¼https%3A%2 2Fwww.cdc.gov%2Fphysicalactivity%2Fbasics%2Fmeasuring%2Findex.html. Accessed January 4, 2019. 31. Epocrates. Osteoporosis. 2018. https://online.epocrates.com/. Accessed December 30, 2018.
Karen D. French, MSN, FNP-C, is an assistant professor at Azusa Pacific University, Azusa, CA, and can be contacted at [email protected]. Donna Emanuele, DNP, FANPBC, FAANP, is an associate professor and director of the DNP program, Western University of Health Sciences, College of Graduate Nursing, Pomona, CA. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.