by Dr. C.H. Weaver M.D. updated 1/2019
A newer treatment option could soon become available for women with osteoporosis. Romosozumab was originally reviewed and denied approval by the United States Food and Drug Administration (FDA) due to safety concerns, but the manufacturers have recently resubmitted a new approval application with additional safety information and the FDA's Advisory Committee has voted in favor of the approval of Evenity (romosozumab) for the treatment of postmenopausal women with osteoporosis at high risk for fracture.
This is the second time romosozumab has been under FDA review. Following an initial application submission in 2017, Amgen and UCB received a complete response letter from the Agency requiring the Companies to investigate the incidence of cardiovascular adverse events that were noted in the ARCH and BRIDGE studies.
Osteoporosis is a disease of the bones that is characterized by reduced bone mass and bone quality. In other words, osteoporosis is characterized by weak, deteriorating bones. Osteoporosis increases the risk of fractures, notably at the hip, spine, and wrist. Although both men and women can develop osteoporosis, it occurs more frequently in women. According to the National Institutes of Health 44 million Americans are affected by osteoporosis and it is most common in Caucasian postmenopausal women.1
About Evenity (RomosozumabAMG 785)
Evenity is a humanized monoclonal antibody that inhibits sclerostin and leads to an increase in new bone formation and reduces bone resorption simultaneously to increase bone mineral density (BMD) and reduce the risk of fracture. Sclerostin is a protein encoded by the SOST and has anti-anabolic effects and is a key inhibitor of bone formation.
The data demonstrating the benefit of romosozumab are compelling and have been reported in the New England Journal of Medicine. (2) In this pivotal clinical trial 7,180 postmenopausal women with T scores of -2.5 to -3.5 at the hip or femoral neck were treated with either romosozumab injections or placebo each month for 12 months, then Prolia (denosumab) for 12 months and directly compared.
The study participants were evaluated 12 and 24 months from initiation of therapy. Vertebral fractures occurred in .5% of romosozumab treated patients compared to 1.8% of placebo treated patients at 12 months. At 24 months only .6% of romosozumab treated patients developed fractures compared to 2.5% of those treated with placebo. Romosozumab also decrease the occurrence of other clinical fractures.
The durability of romosozumab treatment is what is most impressive. The improvement in bone density produced by Prolia is lost fairly rapidly when injections are delayed or missed. The results of the study published in the New England Journal of Medicine suggest that the benefits in BMD achieved with romosozumab are more durable with the clinical benefit actually increasing over time.
The advisory committee reviewed data from nearly 14,000 patients, and voted 18 to 1 in favor approving Evenity. In the currrent Biologics License Application (BLA) resubmission, the indication to treat osteoporosis was narrowed to include only postmenopausal women at high risk of fracture, defined as: history of osteoporotic fracture, or multiple risk factors for fracture; or failed or intolerant to other osteoporosis therapy.
The panel also recommended a "Boxed Warning" related for potential cardiovascular risk stating that romosozumab may increase the risk of myocardial infarction and stroke during treatment and that clinicians should consider the benefit/risk in patients with a history of MI or stroke.
The FDA typically takes the advice of the panel into consideration when making decisions, however it is not bound by their recommendations.
Testing for Osteoporosis
What is a Bone Density Test?
A bone density test measures the density or health of an individual’s bones. A bone density test is the only test that can diagnose osteoporosis before a broken bone occurs. The commonly used tests are non-invasive, painless and usually takes less than 15 minutes to perform.
How is Bone Density Measured?
Currently the best bone density test is a dual energy X-ray absorptiometry (DEXA) scan, also called a bone density scan to measure bone density. The DEXA scan typically measures bone density in the hip and spine by sending a thin, invisible beam of low-dose x-rays with two distinct energy peaks through the bones being examined. One peak is absorbed mainly by soft tissue and the other by bone. The soft tissue amount can be subtracted from the total and what remains is a patient's bone mineral density.
The DEXA compares an individual’s bone density to optimal bone density and produces a measurement called a T-score. A negative T score indicates low bone mass. The World Health Organization (WHO) defines osteoporosis as a T score < -2.5 standard deviations below the mean value of peak bone mass. Osteopenia is a BMD score between -1 and -2.5.
Doctors prefer to measure bone density in the hip and spine because individuals with osteoporosis have a greater chance of fracturing these bones and measurement in the hip and spine can predict the likelihood of future breaks in other bones.
Standard x-rays cannot be used in place of bone density tests. Unlike bone density tests, X-rays are not able to show osteoporosis until the disease is well advanced. However, X-rays can be used in addition to a DXA to detect broken bones in the spine or elsewhere.
What a Bone Density Test Can Do?
A bone density test tells you if you have normal bone density, low bone density (osteopenia) or osteoporosis. It is the only test that can diagnose osteoporosis. The lower your bone density, the greater your risk of breaking a bone. A bone density test can help you:
- know if you have osteoporosis before you break a bone
- predict your chance of breaking a bone in the future
- determine if your bone density is improving, getting worse or staying the same
- determine how well an osteoporosis medicine is working
Who Should Have a Bone Density Test?
The National Osteoporosis Foundation recommends individuals have a bone density test if:
- you are a woman age 65 or older
- you are a man age 70 or older
- you break a bone after age 50
- you are a woman of menopausal age with risk factors
- you are a postmenopausal woman under age 65 with risk factors
- you are a man age 50-69 with risk factors
A bone density test may also be necessary if you have any of the following:
- an X-ray of your spine showing a break or bone loss in your spine
- back pain with a possible break in your spine
- height loss of ½ inch or more within one year
- total height loss of 1½ inches from your original height
Understanding Bone Density Test Results
Your bone density test results are reported using T-scores. A T-score shows how much your bone density is higher or lower than the bone density of a healthy 30-year old adult. A healthcare provider looks at the lowest T-score to diagnosis osteoporosis.
What Your T-score Means. According to the World Health Organization (WHO):
- A T-score of -1.0 or above is normal bone density. Examples are 0.9, 0 and -0.9.
- A T-score between -1.0 and -2.5 means you have low bone density or osteopenia. Examples are T-scores of -1.1, -1.6 and -2.4.
- A T-score of -2.5 or below is a diagnosis of osteoporosis. Examples are T-scores of -2.6, -3.3 and -3.9.
- The lower a person’s T-score, the lower the bone density. A T-score of -1.0 is lower than a T-score of 0.5 and a T-score of -3.5 is lower than a T-score of -3.0.
How Often Should a Bone Density Test be Performed?
People taking an osteoporosis medicine should repeat their bone density test by every one to two years. After starting a new osteoporosis medicine, many healthcare providers will repeat a bone density test after one year.
When repeating a bone density test, it is best to use the same testing equipment and have the test done at the same place each time. This provides a more accurate comparison with your last test result. Although it is not always possible to have your bone density test at the same place, it is still important to compare your current bone density scores to your previous scores.