Diagnosis, treatment of osteoporosis remains complicated

22nd Annual Meeting of NAMS

WASHINGTON, D.C. — A number of factors, including when to search for secondary causes, complicate the process of diagnosing osteoporosis, while new data linking existing therapies to adverse events create difficulties for physicians trying to treat the disease, two presenters said here.

The WHO defines primary osteoporosis as a T-score of –2.5; however, it can be difficult to distinguish between low bone mineral density related to age and postmenopausal changes and low BMD related to secondary causes, according to Steven T. Harris, MD, clinical professor of medicine at the University of California, San Francisco.

“A T-score of –2.5 by the WHO criterion is compatible with — but not diagnostic of — ‘primary’ osteoporosis and doesn’t tell you what the underlying cause is, which is a common source of confusion,” Harris said during a presentation. “Just because the T-score is lower doesn’t excuse you from thinking about other situations.”

Evaluation

Although medical history and a physical examination are typically sufficient for identifying secondary causes, one study showed that approximately 40% to 60% of patients diagnosed with primary osteoporosis will have an underlying issue, according to Harris. Consequently, he said, all patients with low BMD should have at least some degree of laboratory evaluation before treatment.

Currently, no guidelines exist regarding what type of laboratory testing should be performed, but Harris said expert opinion suggests a complete blood count, chemistry panel, 24-hour urine calcium and creatinine levels, 25-hydroxyvitamin D levels, and thyroid function tests, if warranted. While concerns about costs of laboratory examination persist, these tests identify about 92% of new diagnoses at a modest cost and the price of ordering the evaluation is far less than the cost of medications, he noted.

When osteoporosis is unexpected, such as in healthy premenopausal women and men aged younger than 50 years, further testing may be required, according to Harris. He noted the same is true when there is significant bone loss on treatment, without an identified underlying cause. Additional testing may include immunofixation, celiac disease antibodies, HIV screening, biochemical markers of bone turnover and more.

“We want to get away from thinking that a low T-score automatically means treatment with medication,” Harris said. “We need to put in an intermediary step and evaluate for other causes of bone loss, especially those that are serious or correctable.”

Current, upcoming therapies

At present, several treatments for osteoporosis, namely bisphosphonates, have faced a great deal of scrutiny. An association between these drugs and atypical subtrochanteric fractures, osteonecrosis of the jaw and esophageal cancer has given many physicians and patients pause before prescribing and using these therapies, according to Robert Lindsay, MBChB, PhD, of Helen Hayes Hospital and Columbia University, N.Y. Even so, these events are rare, and in high-risk patients and those who have already experienced fractures the benefits likely outweigh the risks, even for long-term treatment. Denosumab (Prolia, Amgen) and zoledronic acid (Reclast, Novartis) effectively reduce the risk for hip fracture, but do not eliminate the risk. Alendronate (Fosamax, Merck) and risedronate (Actonel, Warner Chilcott; Atelvia, Warner Chilcott) also reduce risk for hip fracture as do estrogens. Calcitonin and raloxifene (Evista, Eli Lilly) offer protection against vertebral fracture, and, for raloxifene, reduction in the risk for breast cancer is a bonus for younger women, Lindsay said. However, he strongly cautioned against using two antiresorptive agents at the same time, although teriparatide (Forteo, Eli Lilly) is commonly used with an antiresorptive agent.

Researchers and manufacturers are also exploring novel ways to administer existing drugs such as calcitonin and teriparatide (Forteo, Eli Lilly), Lindsay noted. He also highlighted the development of investigational agents with new targets, such as cathepsin-K inhibitors and a combination of conjugated equine estrogen with bazedoxifene (a tissue selective estrogen combination).

“The treatments we have available produce much greater benefit than harm if used correctly, but conveying that to patients is a problem,” Lindsay said. “Some future therapeutic agents are likely to be effective, but will be subject to similar issues.” – by Melissa Foster

For more information:

• Kagan R. Osteoporosis update: Practical guidance for the care of postmenopausal women. Presented at: the 22nd Annual Meeting of the North American Menopause Society; Sept. 21-24, 2011; Washington, D.C.

Disclosure: Dr. Harris is a consultant, advisory board member or speaker for Amgen, Eli Lilly, Gilead, Merck, Roche, Genentech, Novartis, Sanofi-Aventis and Warner Chilcott. Dr. Lindsay has received grant support from or is a consultant, advisory board member or speaker for Amgen, Eli Lilly, Novartis and Warner Chilcott.

Osteoporosis is a very common disease, and the secondary causes really need to be evaluated. But the workup is fairly simple, and Dr. Harris went over the issues that are important. By using simple evaluations, like complete blood counts, chemical profiles, vitamin D levels and perhaps even a 24-hour urine for calcium, you can find out from these tests if there are secondary causes — the most common being issues related to parathyroid hormone metabolism and sometimes rare diseases that are inherited.

Then, there are nutritional and other common causes as well. We have four good bisphosphonates, monoclonal antibody, estrogen and calcitonin. There are a lot of options for women with osteoporosis. Dr. Lindsay mainly emphasized, however, that the risks that have been reported, such as osteonecrosis of the jaw and atypical fractures, are very rare. To illustrate the point, he said the chances of getting an atypical fracture are akin to being hit by lightning in New Mexico. Therefore, it is best to inform your patients of this. There is another very important point that he made, which is that you should not use two antiresorptives at the same time, and that it is probably a good idea to take a drug holiday for about 1 year if patients have been on bisphosphonates for more than 5 years. Overall, it was a very informative session.

– Michelle P. Warren, MD
Endocrine Today Editorial Board member

Disclosure:Dr. Warren reports no relevant financial disclosures.

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