The author reviews osteoporosis, including basic facts about the disease, risk factors, prevention, diagnosis, and treatment. In addition, the author presents findings of a National Association of Nurse Practitioners in Women’s Health (NPWH) survey* in which 361 nurse practitioners answered questions about different aspects of caring for their patients with osteoporosis, particularly with regard to treatment options and their benefits and risks.

*This survey was conducted with funding from Mission Pharmacal.

In the United States, 40-52 million adults have either osteoporosis or the low bone mass (LBM) that puts them at increased risk for developing osteoporosis.^1,2 Among the 10 million U.S. adults with osteoporosis, about 8 million (80%) are wom­en.³ Data from the 2005-2008 National Health and Nutrition Examination Survey showed that 16% of wom­en aged 50 or older have osteoporosis, and that an additional 61% have LBM at the femur neck or lumbar spine.⁴ According to the National Osteoporosis Foundation (NOF), osteoporosis is responsible for 2 million broken bones and $19 billion in related costs each year.² The NOF predicts that the number of osteoporosis-related fractures will rise to about 3 million by 2025, at an annual cost of more than $25 billion.²

Nurse practitioners who care for women are key to helping change the course of osteoporosis-related fractures in the future. By gaining up-to-date knowledge about osteoporosis and its prevention and treatment, NPs can teach patients at risk for LBM and osteoporosis how to protect their bones. And if either LBM or osteoporosis is identified in any of their patients, NPs can implement optimal treatment to prevent further bone loss and avert fractures. This article not only covers the basics about osteoporosis, but it also provides the results of NPWH’s survey of NPs who are already treating women with osteoporosis. The aims of the survey were to…
• Gain additional insight into how NPs treat osteoporosis in their practice;
• Identify NPs’ educational needs with regard to treatment of patients with osteoporosis; and
• Gather feedback that can be used to design or improve the education provided by NPWH about the care of patients with osteoporosis.

Bone and osteoporosis—the basics

Bone consists primarily of collagen, a tough, elastic protein that forms its framework, and calcium phosphate deposits, which harden and strengthen that framework. As a dynamic tissue, bone is constantly being remodeled; new bone is continuously being formed by osteoblasts and old bone is removed by osteoclasts.⁵ Most people attain their peak bone mass at about age 30, after which the resorption of existing bone slowly begins to exceed the formation of new bone, leading to a decrease in bone mass.¹

Osteoporosis literally means porous bone, which describes the LBM and deterioration that characterize this disease.1 Risk for osteoporosis and its related fractures becomes much higher in women at about age 50, when the level of estrogen, which protects against excessive bone loss, declines and bone loss accelerates.³ Osteoporosis is frequently undetected until one or more vertebrae collapse or a fragility fracture occurs.5

Risk factors

Nonmodifiable risk factors for osteoporosis include female gender, increasing age, and having a small, thin-boned body type.1 Caucasian and Asian women are at higher risk than African American and Hispanic women, although the risk is substantial for all women. Heredity may partially account for an increased risk of LBM and a tendency for fractures.

Modifiable risk factors for osteoporosis include having a treatable condition that raises osteoporosis risk, including amenorrhea in younger women, hypoestrogenemia in older women, anorexia nervosa, and a long history of low calcium and vitamin D intake. Long-term use of glucocorticoids or certain anticonvulsants leads to a loss of bone mineral density (BMD). Other risk factors for osteoporosis that can be altered include physical inactivity, extended bed rest, smoking, and excessive alcohol intake.¹

Prevention

Preventive measures against osteoporosis must be taken across a lifetime. Women need to build optimal peak bone mass by getting enough calcium and vitamin D and exercising when they are young, while avoiding cigarette smoking and excessive alcohol consumption. NPs need to be aware of medications that can decrease BMD and contribute to increased fracture risk.1 These medications include
• Glucocorticoids: used to treat arthritis, asthma, Crohn’s disease, lupus, and other diseases of the lungs, kidneys, and liver;
• Antiseizure drugs, such as phenytoin and barbiturates;
• Gonadotropin-releasing hormone agents used to treat
endometriosis;
• Excessive use of aluminum-containing antacids;
• Certain cancer treatments; and
• Excessive thyroid hormone treatment.

Following a healthful diet and performing regular exercise remain important even after LBM or osteoporosis has developed. NPs need to assess patients’ daily intake of calcium and vitamin D.⁶ NPs should recommend that women older than 50 receive calcium 1,200 mg/day and vitamin D 800-1,000 IU/day from food, and supplement their diet only as needed to make up for any shortfall. Every precaution must be taken to keep living and working areas safe so as to prevent falls, a major cause of fractures.¹

Diagnosis

Several factors in a woman’s health history are key in terms of ultimately identifying LBM and osteoporosis. In addition to basic information such as age and menopausal status, NPs should check for a personal history of broken bones during adulthood, a family history of osteoporosis and fractures, an adequate intake of calcium and vitamin D, regular exercise and physical activity, smoking and/or drinking alcohol, a history of eating disorders or irregular periods, and any health conditions and/or medications that might affect bone mass. Regular thorough physical examinations can document any height loss and identify spinal changes.⁷

If osteoporosis is suspected, NPs can order a central dual-energy x-ray absorptiometry (DXA) scan to measure a patient’s BMD. Diagnosis of osteoporosis is made if a woman aged 50 or older has a T-score less than or equal to –2.5 or if a woman has a history of fragility fractures—regardless of BMD. The T-score represents a way of comparing a patient’s BMD with that of a normal reference person aged 30. Low bone mass is defined as a T-score between –1.0 and –2.5; BMD is considered normal if it is –1.0 or higher. In premenopausal wom­en and younger men, a Z-score is used to evaluate BMD; this score compares the person’s BMD to a reference matched for age. Either score is given as a standard deviation from the BMD used as the norm.6 Medicare covers the cost of a DXA scan every 2 years, or more often if deemed necessary.⁸

A tool to aid practitioners in developing a treatment plan is the World Health Organization fracture risk assessment, or FRAX^®, which helps estimate 10-year fracture risk.⁹ The tool uses an established set of clinical risk factors to compute 10-year fracture risk. FRAX can be used with or without BMD scores. In the U.S., FRAX is especially helpful when determining the best treatment plan for women with LBM but not established osteoporosis. Treatment should be considered for women with low BMD and a 10-year risk of hip fracture of at least 3%, as assessed by FRAX, or a 10-year risk of a major osteoporosis-related fracture of at least 20%, as assessed by FRAX.¹⁰

Treatment

Medications prescribed for prevention and/or treatment of osteoporosis include bisphosphonates, selective estrogen receptor modulators (SERMs), calcitonin, parathyroid hormone (PTH), estrogen, other types of hormone therapy, and an osteoclast or RANK ligand (RANKL) inhibitor.¹ Some bisphosphonates, the RANKL inhibitor denosumab, and teriparatide, the PTH agent, have indications for both women and men, whereas calcitonin, estrogen and other hormone therapies, SERMs, and certain bisphosphonates are approved only for use in women.¹¹ Bisphosphonates are the most common type of anti-osteoporosis medication currently being prescribed.⁶

Because many of the NPWH survey questions dealt specifically with bisphosphonate therapy, the remaining discussion of medications focuses on this class. Bisphosphonates have a great affinity for bone mineral, which helps increase BMD. These agents also inhibit osteoclast activity, thereby slowing bone turnover.¹² Bisphosphonates have proven efficacy in reducing the risk of fractures of the spine, hip, and other nonvertebral sites. In addition, use of these agents has been associated with a significant reduction in morbidity and an increase in survival.¹³

Bisphosphonate products with an FDA indication include alendronate (Fosamax^®, Binosto^®),^14,15 risedronate (Actonel^®, Atelvia^®),^16,17 ibandronate (Boniva^®),^18,19 and zoledronic acid (Reclast^®).²⁰ Alendronate, ibandronate, zoledronic acid, and risedronate as Actonel^® are approved for both prevention and treatment of osteoporosis^14-16,18-20; delayed-release risedronate (Atelvia^®) is approved only for treatment.¹⁷ Ibandronate and delayed-release risedronate have indications for women only^17-19; alendronate, risedronate in Actonel^®, and zoledronic acid are approved for both women and men.^14-16,20 Both formulations of alendronate are taken orally on a weekly basis.^14,15 Risedronate is an oral agent that can be taken weekly, monthly, or on 2 consecutive days each month; dosing differs by product.^16,17 Ibandronate is taken orally on a monthly basis or given intra­ve­nous­ly (IV) every 3 months.^18,19 Zoledronic acid is given IV once a year.²⁰

Oral bisphosphonates are poorly absorbed and, when taken with food, form complexes that cannot be absorbed. Because of this problem, oral bisphosphonates usually must be taken on an empty stomach with plain water,²¹ followed by a 30- to 60-minute delay before ingestion of any food or beverage.^14-16,18 Because of this inconvenient routine, some patients eat and/or drink too soon, thereby negating some or all of the medication effect, or they abandon treatment altogether. Use of IV bisphosphonates can be associated with short-term flu-like symptoms, which occur more often with zoledronic acid than with ibandronate.²²

Two newer bisphosphonate products were developed to avoid or minimize the original problems associated with oral dosing. For patients who do not want to wait to eat or drink, delayed-release risedronate (Atelvia),¹⁷ which also contains a calcium chelator,²¹ is taken immediately after breakfast. For patients who do not want to swallow a pill, an alendronate sodium effervescent tablet (Binosto) has been developed15; the tablet is dropped into a small glass of water to create a strawberry-flavored oral solution.

Rare adverse effects of the bisphosphonates

Over the past several years, a growing body of research has identified an increased risk for atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ) in bisphosphonate users. It is important for NPs prescribing these medications—or hesitating to do so because of the headlines—to know the facts.

Atypical femoral fracture—Most fractures of the femoral shaft are caused by a major trauma. However, a 2005 report initially raised concern about unusual fractures associated with bisphosphonate use.²³ A task force of the American Society for Bone and Mineral research established a list of major features that must be present to classify a femoral fracture as atypical:
• Location anywhere along the femur from just distal to the lesser trochanter to just proximal to the supracondylar flare;
• Association with no or minimal trauma (e.g., a fall from a standing height or less);
• Transverse or short oblique configuration;
• Noncomminuted (not crushed or broken into small pieces); and
• Complete fractures that extend through both cortices and that may be associated with a medial spike; incomplete fractures that involve only the lateral cortex.²⁴

Minor features that are not required for this diagnosis but are sometimes present include bilateral fractures and symptoms, delayed healing, co-morbid conditions (e.g., vitamin D deficiency, rheumatoid arthritis, hypophosphatasia), and use of agents such as bisphosphonates, glucocorticoids, and proton-pump inhibitors, among others.²⁴

Data from a population-based nationwide analysis in Sweden found that the age-adjusted relative risk for AFF in bisphosphonate users was 47.³ and the multivariable-adjusted odds ratio was 33.3.²⁵ However, absolute risk was increased by only 5 cases/10,000 patient-years. A 12-year study showed that although AFF incidence was low, it increased with longer bisphosphonate use.²⁶ A systematic review from the Research on Adverse Drug Events And Reports (RADAR) Project showed that up to 26% of the published cases of AFF in bisphosphonate users had delayed healing or did not heal.²⁷

As a rule, bisphosphonate therapy is considered safe when used for the length of time in the original trials—less than 5 years. Risk for AFFs is increased in patients who have used bisphosphonates for more than 5 years.²⁸ A systematic review of clinical studies of bisphosphonate use in postmenopausal women with osteoporosis found persistent anti-fracture efficacy and increases in BMD beyond 3 years of treatment.²⁹ Some studies in the review showed continuing fracture benefits when patients who had used alendronate or zoledronic acid for 3-5 years discontinued treatment for 3-5 years.

Bisphosphonates are incorporated into bone, allowing them to exert an effect for a time after treatment is discontinued.13 Although there is no formal recommendation for patients at low risk of fracture to take a drug holiday from bisphosphonate therapy, some clinicians think that treatment suspension is appropriate after 5 years.³⁰ However, the benefits of continuing therapy probably outweigh any risk of harm in patients at high risk for fracture—that is, in those with BMD indicating osteoporosis or in those who have sustained a previous fragility fracture.¹³ Once a patient has been identified as having an AFF, bisphosphonate therapy should be discontinued. Initiating teriparatide therapy may help enhance healing of the fractures.²⁸Osteonecrosis of the jaw—Bisphosphonate-related ONJ occurs when the jaw bone is exposed and begins to die because of a lack of a blood supply.³¹ One proposed mechanism has to do with the antiangiogenic effect of bisphosphonates. These agents may limit the angiogenesis that is vital to the development of blood vessels in bone, which has a high turnover rate.³² Prevalence of bisphosphonate-related ONJ is between 1/1000 and 1/100,000 for each year of exposure.³¹ Risk may depend on the bisphosphonate dose, the length of time it has been taken, and the condition for which it has been prescribed. For example, patients with cancer who take IV bisphosphonates are at higher risk for this adverse effect than are patients with osteoporosis taking oral bisphosphonates.³¹

NPWH survey results

In 2013, NPWH surveyed 411 NPs about different aspects of caring for their patients with osteoporosis. These NPs were located in many different areas of the country, including Western (23.8%), Northeastern (21.9%), Great Lakes (20.0%), Southeastern (16.3%), South Central (14.6%), and North Atlantic (3.4%) regions. Among NPs surveyed, almost two-thirds (63.6%) reported working in an obstetrics/gynecology practice. The group had a great deal of experience; 31.9% had been in practice 11-20 years and 26.8% had been in practice more than 20 years. A total of 361 NPs (87.8%) who replied that they treat patients with osteoporosis completed the survey.

Of these 361 survey respondents, 75.6% first counseled their patients about osteoporosis risk as a routine part of well-woman visits, and 18.0% first addressed this risk when a woman became perimenopausal. Of the 361 NPs, more than three-fourths (75.9%) used a BMD test to make the diagnosis of osteoporosis and 23.5% treated patients who had been diagnosed by another healthcare practitioner. In addition to prescribing medication to reduce their patients’ fracture risk, the NPs recommended adequate calcium and vitamin D intake (97.2%), regular weight-bearing exercise (95.3%), cessation of tobacco use (84.2%), and avoidance of excessive alcohol intake (70.9%). The vast majority of the respondents (90.3%) stated that they wanted to receive more education about the diagnosis and treatment of this disease.

As reflected in the literature, most of these NPs (84.8%) prescribed a bisphosphonate as first-line treatment for osteoporosis. The group was almost evenly split between those who felt oral bisphosphonates were of great value as a treatment option (50.4%) and those who felt these agents were of moderate value (47.9%). Although 53.7% of the NPs have maintained their previous level of prescribing bisphosphonates in the past 2 years, 28.3% had decreased their level. Common concerns about prescribing oral bisphosphonates included patient noncompliance (33.8%), gastrointestinal (GI) problems (28.0%), rare side effects such as ONJ (14.4%), and patients’ failure to fill their prescriptions (10.5%). Only 4.7% of the NPs had no concerns about prescribing these agents. About half of the survey group (51.0%) planned to keep patients on bisphosphonate therapy for 3-5 years; 32.4% of the group were not sure.

The NPs were asked to compare different aspects of alendronate, ibandronate, and rised­ronate. Most respondents (73.1%) thought that all three agents had equal efficacy, whereas 18.6% favored alendronate, 6.1% chose risedronate, and 2.2% selected ibandronate as being more efficacious. When asked to compare the agents with respect to the incidence of GI side effects, 76.7% thought that the agents did not differ in this regard and 11.4%, 9.1%, and 2.8% of the group identified alendronate, rised­ronate, and ibandronate, respectively, as having the lowest incidence of GI side effects. Most respondents (80.6%) thought that branded and generic bisphosphonates did not differ in tolerability, whereas 19.4% favored branded products.

The NPs reported several common patient complaints about oral bisphosphonate therapy. The main problems were having to take the pill in the morning on an empty stomach (35.5%), GI side effects (26.3%), dislike of needing to stay upright after taking the tablet (13.0%), difficulty remembering to take the tablets (12.5%), and feeling that the drug was having no impact (5%).

Almost two-thirds of the respondents (63.4%) said that a monthly tablet would likely improve their patient’s adherence to an oral bisphosphonate regimen; 17.5% suggested a weekly tablet and 11.1% chose a daily tablet. Among respondents who favored weekly dosing, 40% preferred a weekly tablet and 60%, a weekly tablet that dissolves into a drinkable strawberry-flavored solution. When asked specifically about the value of this bisphosphonate solution as a treatment option, 61.5% thought that it would be of moderate value, 27.1% felt it would be of great value, and 11.4% saw it has having no value. Among the 361 NPs surveyed, 79.2% were aware of Binosto alendronate sodium effervescent tablets; however, 93.8% of the 145 NPs who replied to this question had never prescribed this product.

Conclusion

Nurse practitioners who treat women with osteoporosis need to be aware of all the treatment options available. Bisphosphonates are still the first-line choice for patients with low BMD and osteoporosis. New formulations have been developed to address concerns that affect adherence to the regimen. Although NPs need to be aware of the rare adverse effects associated with bisphosphonate use, they also need to keep the low absolute risk in mind when deciding whether or not to prescribe these medications.

Susan Rawlins is Director of Education at the National Association of Nurse Practitioners in Women’s Health and practices at the Greater Texoma Health Clinic in Denison, Texas. Ms. Rawlins is a consultant to Mission Pharmacal.

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