Literature Review:
The Efficacy of Bisphosphonates in the Treatment of Osteoporosis in Post-Menopausal Women
Abstract
This paper discusses some of the literature that explores the efficacy of bisphosphonates in the prevention and treatment of osteoporosis among post-menopausal women. This is to determine the ways by which the quality of life of osteoporosis patients can be improved, as advocated by the Healthy People 2020 program. While studies have shown that bisphosphonates are effective in preventing and treating osteoporosis, caution should still be taken with regards to its prolonged use. With this, advanced practice nurses can contribute significantly to the proper administration of the said treatment.
Literature Review
Introduction
Osteoporosis is “the most common metabolic bone disease” (Belizikian, 2009, p. 514). It is a major health problem that affects ten million Americans, with thirty-four million more at risk for it (Whitaker et al., 2012). This in turn results in over two million fractures in the United States every year (Belizikian, 2009) where about half of the women over the age of 50 will incur an osteoporotic fracture in their lifetime (Belizikian, 2009). Fractures that are related to osteoporosis are associated with significant mortality and morbidity and result in disability, chronic pain, and death. In 2005, attendant indirect and direct medical costs reached an estimated $19 billion in the United States alone and this cost is expected to double and triple in the future. As such, early diagnosis and an effective long-term treatment become even more important not only from a medical perspective but also to contain the increasing medical costs.
Because of the positive correlation of bone mineral density (BMD) to bone strength and because it helps in the prediction of future fracture risk, an important part of osteoporosis diagnosis is the dual energy X-ray absorptiometry (DEXA) for the assessment of BMD at the spine and hip. According to the World Health Organization (WHO), osteoporosis is “a hip or spine BMD of ≤ 2.5 SD below normal mean reference values for a young population that
has reached peak bone mass” (Belizikian, 2009, p. 514). In response, the WHO introduced a Fracture Risk Assessment Tool. This enables the prediction of the ten-year probability of a hip or any major osteoporotic fracture in untreated men and women from the age of 41 to 89 with the use of femoral neck BMD and other non-BMD-associated risk factors that include sex, age, excessive alcohol consumption, rheumatoid arthritis, long-term use of glucoticoids., smoking status, parental history of hip fracture, and prior fracture history. If the BMD value is unavailable and the patient has a body mass index (BMI) of less than 21 then this BMI value can also be used as a surrogate marker.
The Use of Bisphosphonates in the Prevention and Treatment of Osteoporosis
According to the National Osteoporosis Foundation (NOF) guidelines (Belizikian, 2009), treatment using pharmacologic agents should be considered for post-menopausal women and for men aged 50 or older who report the following: vertebral or hip fracture; “T-score ≤ -- 2.5 at the femoral neck, total hip, or spine after appropriate evaluation to exclude secondary causes; or low bone mass and a 10-year probability of hip fracture ≥ 3% or a 10-year probability of major osteoporosis-related fracture ≥20% based on the FRAX calculation” (Belizikian, 2009, p. 515).
The main treatment goal for osteoporosis patients is the prevention of fractures through the maintenance and increase of the BMD and through the decrease of excessive bone turnover. Bisphosphonates have been an integral component of different classes of anti-osteoporotic drugs. They have been found to decrease the risk for osteoporotic fractures in a number of clinical trials and have also been found to increase the BMD (Belizikian, 2009). It has been prescribed to over 150 million outpatients from the years 2005 to 2009 (Whitaker et al., 2012)
In the United States, the Food and Drug Administration (FDA) has approved the use of four bisphosphonates for the prevention and treatment of osteoporosis. These include oral alendronate, oral risedronate, oral ibandronate, and intravenous ibandronate. In 2007, intravenous zoledronic acid was also approved.
Alendronate. An oral bisphosphonate, it can be administered either once a day or once a week (Martens & Shaw, 2008). It is indicated for the prevention and treatment of Paget disease of the bone and glucocorticoid-induced osteoporosis in women and men. It is also used to increase bone mass in men who have osteoporosis and to treat and prevent osteoporosis in post-menopausal women.
In the Fracture Intervention Trial (FIT), one study was conducted for three years and involved post-menopausal women with a low neck femoral BMD. Results showed a reduced occurrence of new morphometric vertebral fracture among those in the alendronate group than those in the placebo group (Belizikian, 2009). The study also showed that considerably fewer subjects in the alendronate group had hip fractures compared to those in the placebo group (Belizikian, 2009).
In the other study conducted under FIT, the subjects did not have an initial vertebral fracture at the beginning of the study. It was found that fewer subjects in the alendronate group incurred new morphometric vertebral fractures compared to those in the placebo group (Belizikian, 2009). However, this study showed no significant decrease in hip fractures among subjects in the alendronate group compared to those in the placebo group (Belizikian, 2009). It is notable, though, that in both studies, there was a significant increase in BMD measurements at the femoral spine, hip, and neck among the subjects in the alendronate group than those in the placebo group.
In an extension of the FIT studies, which was called the Fracture Intervention Trial Long-term Extension (FLEX), the effects of the discontinuation or continuation of alendronate treatment for five more years was determined (Belizikian, 2009). Results of the study showed that patients in the alendronate group either had the same or increased BMD levels at the lumbar spine, femoral neck, and hip whereas BMD levels decreased among those in the discontinuation group (Belizikian, 2009). However, it should be noted that the decreases in BMD levels among those in the discontinuation group were still smaller than would have been expected in a person of the same age who had not undergone osteoporosis treatment. In addition, the study showed that the risk of clinical vertebral fractures was considerably reduced in those who continued the alendronate treatment. However, there was no significant difference in the risks of non-vertebral fractures and morphometric vertebral fractures between the continuation and discontinuation groups (Belizikian, 2009).
Risedronate. This is available in dosages of once a day, once a week, or once a month (Martens & Shaw, 2008). It is indicated for the prevention and treatment of the same problems as alendronate.
In two-efficacy VERT (Vertebral Efficacy with Risedronate Therapy) trials, results of the three-year study showed a larger decrease in vertebral and non-vertebral fractures among subjects in the risedronate group than those in the placebo group (Belizikian, 2009). There was also a larger increase in BMD levels among the subjects in the risedronate group than those in the placebo group.
In a two-year extension of these trials, it was similarly found that risedronate treatment led to a significant decrease in the risk for new vertebral fractures, as well as to the maintenance or increase of BMD levels at the hip and spine (Belizikian, 2009).
Oral ibandronate. This is available as either a daily or a monthly tablet (Martens & Shaw, 2008). It is indicated for the treatment and prevention of osteoporosis in post-menopausal women and has been found to increase BMD and decrease the incidence of vertebral fractures (Martens & Shaw, 2008).
The Oral Ibandronate Osteoporosis Vertebral Trial in North America and Europe (BONE) established the three-year efficacy of oral ibandronate in post-menopausal women with osteoporosis (Belizikian, 2009). This study showed a higher decrease in new morphometric verbal fractures among the subjects of the daily dosing group compared to the placebo group and those who received intermittent dosing (Belizikian, 2009). There was also a higher decrease in clinical vertebral fractures among the subjects of the daily dosing group compared to the placebo group (Belizikian, 2009). In addition, BMD levels at the lumbar spine and hip had a higher increase for those in the daily dosing group (Belizikian, 2009). However, there was no significant difference in the risk of non-vertebral fractures in either the daily dosing or in the intermittent dosing groups (Belizikian, 2009).
In another study called the Monthly Oral Ibandronate in Ladies (MOBILE), it was found that a monthly oral ibandronate dosage of 150 mg significantly increased total hip and lumbar BMD more than a daily dose of 2.5 mg did in post-menopausal women with osteoporosis (Belizikian, 2009).
Intravenous ibandronate. This can be administered once every three months as a fifteen- to thirty-second bolus. It is indicated as a treatment for osteoporosis in post-menopausal women and has been found to produce higher increases in BMD levels than the daily oral treatment (Martens & Shaw, 2008).
In a trial called the Dosing Intravenous Administration (DIVA), the effects of oral ibandronate on BMD levels were compared to those of intermittent injections of ibandronate (Belizikian, 2009) where the participants of the study consisted of post-menopausal women with osteoporosis. After one year, results of the study showed that there were greater BMD changes in the intravenous groups than in the oral treatment group (Belizikian, 2009).
Zoledronic acid. This is an approved treatment for osteoporosis in post-menopausal women where dosing needs only a single yearly 15-minute infusion (Martens & Shaw, 2008). A study called the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) – Pivotal Fracture Trial assessed the efficacy of a single fifteen-minute infusion of 5 mg of zoledronic acid every twelve months over a period of three years (Belizikian, 2009). Results showed that once-yearly zoledronic acid infusions resulted in a higher decrease in the incidence of morphometric vertebral fractures as well as in the incidence of hip fractures compared to the placebo group (Belizikian, 2009). In the same manner, multiple morphometric verbal fractures, clinical vertebral fractures, all clinical fractures, and non-vertebral fractures also decreased significantly for the zoledronic acid group compared to the placebo group (Belizikian, 2009). Moreover, BMD levels at the femoral neck, lumbar spine, and total hip increased by higher levels compared to the placebo group (Belizikian, 2009). As well, a study by Jansen, Bergman, Huels & Olson (2010) showed that of the bisphosphonates that are available for osteoporosis treatment, zoledronic acid has the highest probability of providing the best overall protection against fracture.
Recent findings have shown that prolonged use of bisphosphonates led to higher risks of fractures compared to those who switched to placebo (Whitaker, 2012). Although this matter is still being investigated, it is safer for now to limit its use. Similarly, the most concerning adverse effects of bisphosphonates when used for osteoporosis treatment is gastro-intestinal intolerance (Hooper & Davis, n.d.). Moreover, other adverse effects caused by alendronate treatment include diarrhea, constipation, nausea, musculoskeletal pain, and abdominal pain (Hooper & Davis, n.d.).
Studies have found nitrogen-containing bisphosphonates – such as alendronate, risedronate, and ibandronate -- to be “potent inhibitors of osteoclastic bone resorption and share, as a class, similar pharmacological properties” (Bock & Felsenberg, 2008). With an overall beneficial safety profile and a proven efficacy, nitrogen-containing bisphosphonates are considered the first choice in the treatment of post-menopausal osteoporosis. However, Bock & Felsenberg (2008) suggest that the effects of bisphosphonate treatment in individual patients as well as its cost-effectiveness from the perspective of public health are reliant on patient persistence, compliance, and adherence. To improve patient adherence, Bock & Felsenberg (2008) proposed the extension of dosing intervals for oral regimens to weekly or monthly or to administering the treatment using an IV instead.
Conclusions and Recommendations
The literature discussed in this paper attempted to answer the question of whether bisphosphonates can be used as an effective means of preventing and treating osteoporosis and hip fractures. As shown by several studies that were discussed n this paper, bisphosphonates -- particularly, alendronate, oral risedronate, oral ibandronate, intravenous ibandronate, and intravenous zoledronic acid -- do help in the prevention of osteoporosis and hip fractures among post-menopausal women. Although there are still questions about how much bisphosphonate treatment should be administered to a patient, its use in the management of osteoporosis patients should be worthy of further investigation.
With proper administration, bisphosphonates can be used to significantly improve the quality of life of osteoporosis patients. This would be in adherence to the goals of Healthy People 2020, which is to help people attain a high-quality and longer life that is free from injury, disability, preventable disease, and premature death (Centers for Disease Control and Prevention, n.d.). In relation to osteoporosis, this program aims to reduce the mean level of pain, hip fractures, the unemployment rate that’s caused by the disease, and the activity limitation due to the same (Missouri Regional Arthritis Centers, n.d.)
Advanced practice nurses can help in this initiative by making sure that the patient's condition is constantly and regularly monitored and assessed. As advanced practice nurses, part of their role would be to perform complete physical examinations on the patient, with special attention given to weight height, posture, mobility, the thyroid, and the neurological and muskoskeletal systems (Hansberger, 2007). The advanced practice nurse must also perform screening measures for the determination of the degree of bone loss and the risk for fracture. Similarly, the effects of bisphosphonate treatment should be monitored and the dosing adjusted accordingly. In addition, the advanced practice nurse should educate the patient with regards to behavioral and lifestyle changes, which would be essential for effective treatment. Furthermore, as indicated by the National Osteoporosis Foundation guidelines (Medscape Medical News, 2008), bisphosphonate treatment should be considered for women who are 65 years old and above; have multiple risk factors for osteoporosis; and are not undergoing hormone replacement therapy.
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