New model makes diagnosing osteoporosis easier

As any expert will tell you, osteoporosis is complex and hard to predict. Most clinicians treat it only when they detect low bone density, viewing this as the definitive test. But machines to detect low bone density are expensive and far from universally available. Moreover, bone density measurements may not adequately predict osteoporosis. Therefore, given the paucity of diagnostic options, millions face unknown threats of debilitating fractures, while others may receive treatment they may not need.

Now, researchers at the World Health Organization’s Collaborating Center for Metabolic Bone Diseases in Sheffield, UK hope to make osteoporosis prediction more accurate and accessible. A new model described at the IOF World Congress on Osteoporosis in Toronto, Canada, identifies susceptible people according to country-specific risk factors, including age, height, and weight, among several others (conference abstract PL2). By integrating these factors, the model predicts the likelihood of hip and other osteoporotic fractures over ten years.

Osteoporosis fracture risk varies worldwide by as much as ten-fold, said presenter John Kanis, the Center’s director, who suggests higher risks in wealthier countries may reflect more sedentary lifestyles. “The model will be calibrated to specific countries and individuals according their specific risk profiles,” he said. “Our goal is to identify people who genuinely face a high risk of fracture in addition to those who don’t, so that treatment can be more optimally directed.”

Obesity Harms Bones

In a different presentation, Dr. Hong-Wen Deng of the University of Missouri, in Kansas City, and colleagues from China, showed that obesity can accelerate bone loss (conference abstract P152). The finding undermines prior assumptions that obesity—a risk factor for everything from diabetes to heart disease—made skeletons stronger and more resistant to fractures. But Deng’s research showed that the bone strengthening benefits of a heavy body aren’t due to fat, as some might have assumed, but to elevated muscle mass, which increases bone density. Higher fat content, ironically, was linked to weaker bones, which are more prone to fractures. “This is quite contrary to conventional wisdom that a heavier body per se helps reduce the risk osteoporosis,” Deng said. “We conclude that reducing obesity is good for osteoporosis care.”

Deng and colleagues compared measures of fat, lean mass (i.e. muscle mass), and total body weight with measures of bone density in 1,988 Chinese and 4,489 Caucasian subjects. Lean mass was found to be positively associated with high bone density, reinforcing Deng’s view that patients should build bone strength by building muscle, not by gaining weight through fat accumulation. Along similar lines, obese individuals could lessen their osteoporosis risk by losing fat, either with lifestyle changes, or in the future with drugs that block genetic factors leading to obesity. Thus, fat loss and osteoporosis prevention are, in fact, linked by shared goals to improve health. Calling the finding a “challenge to current dogma,” Deng emphasized that additional research is needed to replicate the results in other populations.

Along these lines, a meta-analysis by John Kanis of the University of Sheffield, UK, included within the WHO’s new Fracture Risk Assessment Guidelines finds thinness is a fracture risk, but obesity, on the other hand, is not protective.

Predicting Osteoporosis in Middle Age

Meanwhile, presenter Anna Holmberg, of Malmö University Hospital, Sweden showed that fracture risk in both men and women can be predicted during middle age.Osteoporosis interventions usually focus on the elderly, who are by far the most vulnerable among the population. Holmberg’s findings suggest prevention opportunities can start with much younger people. “If we can identify middle-aged individuals who are at risk then we can treat them before they get fractures,” she said.

The researchers reviewed data for 22, 444 men and 10,902 women recruited by Malmö Preventive Project, a prospective study of cardiac health that was initiated in Sweden in 1974. At the time of recruitment, the subject’s ages ranged from 44 to 50. Now, more than 30 years later, baseline characteristics could be matched with fracture incidence over time.

Holmberg and her colleagues found that fracture incidence began climbing steadily at age 60. The most reliable predictors included diabetes, physical frailty, mental illness, and excessive alcohol consumption.

Diabetes, in particular, was strongly linked to elevated fracture risk; even more than among the elderly. “The link with diabetes was much stronger than we anticipated,” Holmberg said, adding that vertebrae, ankle, and hip bones are especially vulnerable. “Diabetes can impair vision, making individuals less steady on their feet,” she explained. “It also disturbs intestinal calcium uptake and vitamin D metabolism.”

Among men, prior hospitalization for mental illness was strongly linked to all types of fractures. Data limitations prevented Holmberg from determining why the mentally ill appear to be at elevated risk. However, she suggests they might, on average, lead more dangerous or violent lives with more fracture opportunities.

SSRIs May Increase Fracture Risk

An additional study found that drugs used to treat depression and other mental illnesses may heighten the risk of fractures. Dr. Brent Richards from McGill University, working with researchers in the Canadian Multicentre Osteoporosis Study (CaMos) presented the findings. According to the study’s results, daily use of selective serotonin reuptake inhibitors (SSRIs)—which rank among the most widely prescribed drugs in the world with combined annual sales of US $8.3 billion— were associated with an elevated risk of X-ray confirmed fragility fractures among subjects aged 50 years and above. “The take home message is that SSRI use, depression and fractures are common in the elderly,” Richards said. “So, given these high prevelances, the effect of SSRI use on fractures may have important public health implications.”

Prior studies by other researchers dating back to 1998 also linked fractures and SSRI use. However, these earlier studies failed to adequately address the role of potential confounders, Richards said. Although care must be taken in the interpretation of any observational study, to help to isolate SSRI effects, the current study controlled for age, sex, bone mineral density (BMD), falls, cigarette smoking, nutrition, and many other factors that can also exacerbate fracture risk. SSRIs in particular are known to be associated with low BMD and increased risk of falling. But even after accounting for falls and low BMD, SSRIs produced a two-fold elevation in fracture risk, leading the CaMos researchers to suspect that other, unknown mechanisms are at play. “It’s important to note the study was done in older subjects,” Richards said. “For younger individuals, the risk of fractures associated with SSRIs is likely to be smaller. But if you’re over 50 years of age and at an increased risk of fracture, then SSRIs may increase this risk further. On the other hand, one must also consider that the treatment of depression may confer substantial benefit to patients with this condition.”