Who should be treated for bone loss? What is the FRAX® algorithm and how is it used? What types of medications are usually prescribed for osteoporosis and osteopenia?
If you are told you have osteopenia or are diagnosed with osteoporosis, calcium and vitamin D supplementation with appropriate exercise may not be enough to decrease bone loss or to build bone. You may need a prescription medication. Some medications are only prescribed for women, and others are prescribed for both women and men.
If your T-score is in the osteoporosis range, your clinician will likely recommend medication in addition to lifestyle changes such as exercise and adequate intake of calcium and vitamin D. Most clinicians also agree that if your T-score is in the osteopenia range of -2.0 or lower or if your T-score is —1.0 to -2.5 and you have also had a low-trauma fracture, you should be treated with medication and lifestyle changes. However, consensus has been lacking about whether to start medication therapy for individuals with T-scores in the —1 to -2 range or when risk factors other than low-trauma fracture are present.
The World Health Organization (WHO) recognized the lack of consensus about treatment for people with low bone mass (T-score —1.0 to -2.5). To assist with determining who might benefit from starting medication therapy, the WHO developed the Fracture Risk Assessment Tool (FRAX®) algorithm to identify the 10-year probability for having a hip fracture or major osteoporotic fracture (i.e., spine, hip, forearm, or humerus [upper arm bone]).
The algorithm is available online (shef.ac.uk/ FRAX/), and users can identify a specific country and language. United States users specify among four different ethnic/racial groups: Caucasian, Black, Hispanic, or Asian. Risk factor information is entered for 11 different risks (see Box 1) and the femoral neck raw BMD value in g/cm2 (or the total hip can be substituted if the femoral neck is not known; other site
Risk Factors Used for the WHO FRAX Online Algorithm
• Age and date of birth
• Cigarette smoking status (yes/no)
• Femoral neck BMD score in g/cm2; specify DXA or other type of measure
• If parent ever had a hip fracture (yes/no)
• If three or more units of alcohol are consumed per day (yes/no)
• If patient has history of prior fracture (yes/no)
• Patient's height in centimeters
• Patient's weight in kilograms
• Presence of rheumatoid arthritis (yes/no)
• Presence of secondary osteoporosis (yes/no)
• Sex (male/female)
• Use of glucocorticoid medications (yes/no)
BMD values cannot be used because the tool has not been tested using values from other sites).
The FRAX algorithm is user-friendly. Position your computer cursor over the "Calculation Tool" area on the top banner, move down to click on the United States country group, and select the appropriate ethnic/racial subgroup. Next enter the appropriate values for each of the 11 risk factors and your raw hip BMD value in g/cm2. Specify if the test was a DXA or other type, then click on "Calculate" to identify your personal 10-year risk for hip or major osteoporotic fracture. Height and weight must be entered as centimeters and kilograms. The FRAX site provides a conversion tool from inches to centimeters and pounds to kilograms on the same Web page, located on the far left of the computer screen (see Figure 11).
The FRAX results are intended to assist with clinical decision making and do not provide a definitive result for clinicians to follow. The tool uses several risk factors that are known to be important for bone health (see Box 1), but other factors are also important. Additionally, some of the factors that are included are entered simply as yes or no responses when in reality the amount is important. For example, long-term
Figure 11 FRAX® algorithm.
Source: Image used with permission of the WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield. FRAX® is registered to Professor JA Kanis, University of Sheffield.
steroid use is entered as yes or no, but in clinical practice it is known that higher doses of steroids have greater effects on bone than do lower doses.
The FRAX algorithm is used by clinicians to identify who might benefit from starting medication therapy for bone loss, and it is specifically intended for patients whose BMD levels fall in the low bone mass category (-1.0 to -2.5) and who have not used medication previously. The current version of the FRAX is in a test, or "beta," format and will be changed in the future after it has been used clinically and problems or necessary changes are identified. For the present, it is a very useful tool for assisting with clinical decisions about who might benefit from using medication. FRAX results are expected to be included in BMD test reports to clinicians by the end of 2009 (see Question 33). Studies have determined what thresholds of the FRAX results for both hip and major osteoporotic fracture are cost-effective on a population basis for starting medication treatment.
Based on this information, the National Osteoporosis Foundation (NOF) set clinical recommendations for starting medication if you are a postmenopausal woman or a man over 50 if you have:
• A BMD T-score at the total hip, femoral neck, or spine of -2.5 or lower and no other causes of bone loss ("secondary osteoporosis")
• Fracture(s) at the spine (either identified on x-rays or other tests or by clinical examination) or at the hip
• Previous fracture(s) at other sites together with low bone mass (T-score of -1.0 to -2.5) at the hip or spine
• Low bone mass (T-score of —1.0 to -2.5) at the spine or hip together with secondary causes that are associated with high risks for fracture (e.g., use of glucocorticoids, immobilization)
• Low bone mass (T-score of—1.0 to —2.5) at the spine or hip together with a FRAX calculated 10-year fracture probability at the hip of 3% or higher or for any major osteoporotic fracture of 20% or higher
The types of prescription medication used fall into two categories. The first category of medications is called antiresorptive agents. They are intended to work on the osteoclasts to inhibit bone resorption, meaning that the medications interfere with the cells that are trying to break down old bone. Estrogen therapy (ET) is one of these types of medications and for postmenopausal women has been found to be very effective in the prevention of osteoporosis. ET is appropriate for preventing osteoporosis in postmenopausal women who are experiencing significant menopausal symptoms (see
Questions 64—66). Other medications that fall into the group of drugs intended to prevent further loss by slowing down the breakdown of bone include bisphosphonates, calcitonin, and estrogen agonists/antagonists (which used to be known as selective estrogen receptor modulators [SERMs] until September 2007 when the FDA changed the terminology). Questions 56 to 65 contain a full discussion of each drug. Although the medications do not make new bone directly, they do assist in increasing bone density by slowing down the rate at which old bone is broken down. In each question, specific information about the bisphosphonate medications are presented. It is important to note that a recent study identified that all of the bisphosphonates are basically equally beneficial in treating bone loss. Some differences in specific studies may have been caused by the numbers of patients who participated, time for the study overall, how data were collected or reported, and so forth. In the end, bisphosphonates, as well as the other treatment choices for bone loss, are extremely effective options. Discussing the various possibilities with your clinician and taking into account what will fit into your life, such as a daily versus monthly pill, an intravenous infusion, or a subcutaneous injection, are very important, as staying on the medication is what relates most strongly to how well it works.
There currently is only one FDA-approved medication in the second category of medications used to treat osteoporosis. This medication is called an anabolic agent, which works with osteoblasts to actually build bone (see Question 62).
The most important thing for you to remember is that prescription medications do not usually contain calcium or vitamin D; however, Fosamax (alendronate) Plus D does contain vitamin D and Actonel (risedronate)
Bisphosphonates must be taken alone, on an empty stomach, with a plain glass of water first thing in the morning or when you are up for the rest of the day.
with Calcium does contain calcium. Fosamax Plus D contains 2800 IU of vitamin D, a week's worth of vitamin D. Actonel with Calcium is a new way of packaging the once-weekly Actonel dose. The package includes 4 weeks of medication. Each week has one 35-mg Actonel tablet and six 1250-mg calcium carbonate tablets (500 mg elemental calcium each) to take on the days that Actonel is not taken. Even if you take the prescription medication faithfully, you will not get the full benefit of its effects without getting adequate calcium and vitamin D in your diet or by supplements. So, make sure that your prescription medication has a chance to work by remembering to take the necessary amount of calcium and vitamin D. If you are prescribed a bisphosphonate, you must NOT take calcium and the medication at the same time. Bisphosphonates must be taken alone, on an empty stomach, with a plain glass of water first thing in the morning or when you are up for the rest of the day. You must not lie down or eat or drink anything else for 30—60 minutes, depending on the specific medicine. You must take your calcium later. Further instructions on how to take bisphosphonates appear in Questions 56 to 60.
Adherence with taking any medication prescribed for you is very important. A recent study showed that the majority of women stop taking their prescribed bisphosphonate medication before 1 year is up and, although weekly dosing was better than daily dosing, many on weekly dosing still did not stick to their medication regimen. The researchers speculate that there are two reasons why women don't stay on their bisphosphonate medication regimens. First, osteoporosis is a chronic disease, but you can't see it or feel it unless you fracture a bone, so it may be difficult to justify the expense for medications and establish the ongoing routine for taking them. Secondly, because it is necessary to follow strict guidelines when taking the medication either daily or weekly, sticking to the regimen can be trying. The obvious downside to not taking your medication regularly, whether it's a bisphosphonate or something else, is that you will not benefit from its intended effects. You will not improve your bone mineral density and your fracture risk will continue to increase (see Table 7).
Table 7 Summary of Prescription Products for Osteopenia and Osteoporosis
Certain groups of people should receive prescription medications for the prevention and treatment of osteoporosis. According to the American College of Rheumatology, bisphosphonates (see Questions 56-58) should be prescribed to the following groups who are receiving glucocorticoid therapy (such as for rheumatoid arthritis, asthma, inflammatory bowel disease, or lupus):
• To prevent bone loss in individuals in whom long-term glucocorticoid (steroid) treatment (doses of 5 mg or more per day) has been initiated
• Patients who already have GIO with documented low bone mineral density or recent fracture
• Patients receiving glucocorticoids who have sustained fractures while on estrogen therapy or in whom estrogen therapy has not been well tolerated.