Increased Bone Risk in MS Patients Even Early in Disease Course

Barbara Boughton

July 26, 2011 — It has long been known that patients with long-standing multiple sclerosis (MS) are at increased risk for low bone mass, osteopenia, and osteoporosis and, as a result, may incur health-threatening fractures.

Now a new study from Norwegian researchers is the first to report that even patients with early-onset MS or clinically isolated syndrome have increased risk for osteopenia, osteoporosis, and low bone mineral density (BMD).

These findings, published in the July 12 print edition of Neurology, suggest that MS and low bone mass may share a common origin and pathologic features, including vitamin D insufficiency, increased activity of inflammatory cytokines such as interleukin 6, and low levels of the protein osteopontin, the Norwegian researchers said.

The results of the study may also indicate a need for physicians to take a more active approach toward preventing osteoporosis early in MS, they write.

"We have shown that the process that results in low bone mass either starts very early in MS or patients may have lower than average bone mass even prior to the disease," said Trygve Holmøy, MD, PhD, professor of neurology at the University of Oslo in Norway and senior author of the study. "Low vitamin D levels may predispose patients to both low bone mass and MS."

Shared Etiologic Factors?

In the study, 99 consecutive patients newly diagnosed as having clinically isolated syndrome or MS with an average age of 37 years were matched with 159 case controls of similar age, sex, and ethnicity — with one control group drawn from Norway's National Population Registry and the other comprised of subjects who were recruited by patients but who were not family relatives.

The MS patients had BMD tests an average of 1.6 years after they had any symptoms that suggested the presence of MS, and all had no or minor physical disability from the disease.

Results revealed that 50.5% of the MS patients had osteopenia (defined as a T score <-1 to <-2.5 or osteoporosis (defined as a T score =-2.5) in at least 1 skeletal site vs 37.1% of controls (P = .034). Even after the researchers adjusted for confounders such as smoking history and alcohol use, the results remained significant, Dr. Holmøy said.

The researchers acknowledged that the study's limited size prevented analysis of sex- and age-specific associations between MS and BMD. By creating 2 control groups, the researchers hoped to control for selection bias, they said.

Still the study is one that needs to be replicated in larger studies with different populations from the MS patients in Norway. "The results might be different for other populations living at different latitudes," Dr. Holmøy said.

The next step for the researchers will be to analyze biochemical data for the study population to assess whether the MS patients had increased bone turnover compared with controls, Dr. Holmøy added.

Pay Attention to Bone Health

"This study is an interesting one," commented Barbara Giesser, MD, clinical professor of neurology and medical director of the Marilyn Hilton MS Achievement Center at the University of California, Los Angeles. "It suggests that the development of osteoporosis and osteopenia in MS may not just be tied to factors such as immobility. There may be shared etiologic factors at work early in the course of MS that contribute both to the disease's pathophysiology as well as to the differentiation of bone cells."

Dr. Giesser noted that although the Norwegian study was relatively small, it was also carefully performed. It also spotlights the need for more research into the role of vitamin D and osteopontin in the pathophysiology of MS, Dr. Giesser said.

"Yet the overwhelming take-home message for physicians from this study is to pay attention to bone health early on in the course of MS," Dr. Giesser said.

For Dr. Holmøy, such active management would include BMD measurements in the first few years of the disease. "Patients who have a tendency to fall or who have low bone mass should then have a [second] BMD scan within the next few years," he said.

As well as performing weight-bearing exercises, physicians should work to make sure that MS patients supplement their diet with enough vitamin D. "Bisphosphonates should also be considered in MS patients with particularly low bone mass," Dr. Holmøy said.

The study was funded by research grants from the South-Eastern Norway Regional Health Authority, Ulleval University Hospital, the Odd Fellow Research Foundation for Multiple Sclerosis, the endowment of K. and K.H. Hemsen, and the endowment of Fritz and Ingrid Nilsen. Dr. Holmøy has received funding for travel and speaker honoraria from sanofi-aventis, Merck Serono, Biogen Idec, Bayer Schering Pharma, and Novartis. Dr. Giesser has disclosed no relevant financial relationships.

Neurology. 2011;77:151-157.

Authors and Disclosures

Barbara Boughton