Just as a heart attack is a serious failure of the cardiovascular system, a fragility fracture signals a failure of the skeletal system. Just as no clinician would fail to assess and treat the underlying risk factors in a patient with a myocardial infarction, any bone fracture in an older patient calls for an evaluation for osteoporosis and possible treatment, says Suzanne Jan de Beur, MD, associate professor of medicine at Johns Hopkins University School of Medicine and director of endocrinology, diabetes, and metabolism at the Johns Hopkins Bayview Medical Center, in Baltimore.
The disturbing clinical outcomes of hip fractures in patients over 50 highlight the dangers involved — a 25% one-year mortality rate, with 50% of patients never returning to their previous levels of function.
And the common impression that this is a women’s disease can lead to missed diagnoses, considering that a fifth of the cases are men. “Of the two million fractures each year due to osteoporosis, about 600,000 are in men,” says Nelson Watts, MD, director of Mercy Health Osteoporosis and Bone Health Services in Cincinnati and lead author of an Endocrine Society guideline on osteoporosis in men. Men are diagnosed on the order of 10 years later in life than women, which can make a broken hip that much more problematic. And the number of cases in both sexes can be expected to increase as the population ages.
Given that most of the conditions endocrinologists deal with have implications for calcium metabolism and hence bone, they should be more involved in bone management and not leave them to other specialties, Watts urges.
Developments and Controversies
Diagnosis and treatment continue to improve and evolve, along with recent developments and controversies, including disagreements about calcium and vitamin D supplements, recommendations for a drug holiday from osteoporosis treatment, improved results from combining current drugs, and promising medications on the horizon.
Diagnosis is more accurate than ever with the advent of the World Health Organization’s sophisticated online Fracture Risk Assessment Tool (FRAX) for calculating a patient’s risk by taking into account many factors in addition to a T-score from a DXA bone scan. Because two-thirds of vertebral fractures are asymptomatic, recent guide- lines from the National Osteoporosis Foundation also point out the utility of examining spine x-rays for occult fractures for a better picture of a patient’s fracture risk, according to Jan de Beur.
Supplemental Questions
Although some studies and many mainstream media reports have raised issues about the value of calcium supplements and their potential association with cardiovascular events, bone experts do not question their role in treating osteoporosis. Watts notes that calcium is the raw material for building bone, so it is hard to believe one could maintain good bone without it. Although there is no clear evidence that calcium sup- plements benefit the general population, studies show that the combination of calcium and vitamin D reduces fractures in people with osteoporosis. Pauline Camacho, MD, director of the Loyola University Osteoporosis and Metabolic Bone Disease Center in Maywood, Ill., recommends a daily calcium intake of 1,200 mg from all sources to help prevent bone loss, which is the level recommended by the Institute of Medicine (IOM) for women over 50.
Watts and Jan de Beur concur with this recommendation, and all three experts noted the importance of taking a dietary history. Although they questioned the studies showing increased cardiovascular risk from calcium supplements, they agreed that the wisest course is to aim for a daily total calcium intake of about 1,200 mg but not to exceed it to avoid potential pitfalls of high intake, such as kidney stones. Jan de Beur recommends dietary adjustments to increase patients’ calcium intake, preferring dietary calcium to supplements because it is accompanied by other nutrients. “There are no studies that demonstrate that dietary calcium is associated with coronary events, and some studies show there is a protective effect,” Jan de Beur says. Supplements should make up for any dietary shortfalls.
The Vitamin D Conundrum
The question of how much vitamin D is enough has been the subject of dueling guidelines in recent years. The IOM recommended a vitamin D blood level of 20 ng/ml, but shortly thereafter the Endocrine Society published a guideline recommending a level of 30 ng/ml to not simply avoid deficiency but to ensure sufficiency.
Jan de Beur and Watts say that the IOM guideline was population based, and regardless of its role in the general population, vitamin D is an important nutrient for people concerned about osteoporosis. “In the bone field, we have clung to the idea that you’d like to have a level of at least 30 ng/ml,” Watts says. Jan de Beur aims for a level of 32 ng/ml, whereas Camacho shoots for levels in the 40s or 50s. Camacho says that vitamin D has a very wide therapeutic range, with literature reports of toxicity usually associated with levels in the 150 ng/ml range. She leaves herself a cushion because of the variability of laboratory assays. Because dietary vitamin D is elusive, there is no controversy about turning to supplements.
Drug Holiday
Another current concern relates to how long to maintain continuous treatment with the most commonly used drugs, bisphosphonates. Bones are constantly being remodeled through the formation of new and the resorption of old tissue. Bisphosphonates’ benefits are based on slowing bone resorption, but they slow creation at the same time. After several years of treatment, the benefits diminish, and, although the problems remain rare, there is an increase in osteonecrosis of the jaw and atypical fractures of the femur (mid-femur fractures not involving a fall).
“One of the unique things about bisphosphonates is that they accumulate in bone, and so even after we stop giving them, there is a reservoir from which the drug continues to be released, and can provide a lingering benefit,” Watts says. And although clinicians lack hard data for making their choices, left with the challenge of balancing risks of osteoporosis versus risks of treatment, guidelines are endorsing the concept of a drug holiday.
Jan de Beur says it is unlikely long-term studies will settle the issue, so “we are going to have to rely on expert opinion” and clinicians’ practices vary. She reassesses her patients on oral bisphosphonates after five years. If their bone density is stable and they have an acceptable T-score, she gives them a drug holiday until there is a reason to restart it, such as a drop in bone density, a fracture, or an increase in bone resorption markers. Some physicians simply use a set time period off . Jan de Beur keeps patients with severe osteoporosis on bisphosphonates for 10 years, but avoids exceeding that time. Camacho treats patients with a low or moderate risk of fracture for five years, and then gives them a holiday. She treats patients who are elderly or severely affected for 10 years, then gives them a very brief holiday.
Watts says the approach can vary by the specific drug being used, with high-risk patients benefiting from 10 years of treatment with oral alendronate but six years being adequate with zoledronic acid. “Our approach is to monitor bone density, and in the lower risk patient, continue the holiday until the bone density shows a significant drop. In the higher risk patients, we restart treatment after two years off, regardless of how well things are going, and
restart after a year off if bone density drops,” he says.
For treatment of those higher risk patients with severe osteoporosis, recent studies are finding better results by combining treatments. Denosumab is another “antiresorptive,” but it works in a somewhat different fashion from the bisphosphonates. A RANK ligand inhibitor, it interferes with a primary source of the signal for bone removal. Teriparatide is a parathyroid hormone fragment, and is the only drug approved in the U.S. aimed at bone formation. Recent studies show that in combination, the two have additive effects.
Added Role for Endocrinologists
Fractures are often considered the province of orthopedics and bone scans of rheumatology, but narrow interpretations can overlook the myriad conditions that can lead to weakened bones. “Almost any endocrine disorder you can think of has some effects on bone, including Cushing’s disease, diabetes, overtreatment with glucocorticoids for Addison’s disease or other adrenal insufficiency, hyperparathyroidism, hypopitiutarism that leads to deficiencies in gonadal steroids, and hypogonadism. It’s hard to think of an endocrine disease that doesn’t in some way have some effect on calcium,” Watts says. So diagnosis should include a comprehensive evaluation for causes of secondary osteoporosis — which is another reason endocrinologists should take greater interest in and ownership of the condition.
— Seaborg is a freelance writer based in Charlottesville, Va. He wrote about the Affordable Care Act in the January issue.
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