• by Nancy Walsh 
  Senior Staff Writer, MedPage Today

  September 12, 2016

Action Points

Women with gout have a modestly increased risk of hip fracture, a prospective observational study found.

In an analysis of data from the Nurses' Health Study, a history of gout was associated with a higher risk of hip fracture after adjustment for age, with a relative risk of 1.40 (95% CI 1.16-1.69), according to Julie M. Paik, MD, and colleagues from Harvard Medical School in Boston.

And in a multivariable analysis that adjusted for numerous factors including body mass index (BMI), race, smoking, physical activity, nutrient intake, medications, and co-morbidities, an association of gout with hip fracture remained significant (RR 1.38, 95% CI 1.14-1.68), the researchers reported online in Arthritis & Rheumatology.

Previous research has suggested that uric acid can influence bone health either through antioxidant or pro-oxidant mechanisms.

"When uric acid exists at supersaturated concentrations such as in gout, then its antioxidant properties could be overcome by its pro-oxidant effects and create an environment of high oxidative stress," Paik and colleagues explained.

"The pro-oxidant role of uric acid can contribute to an inflammatory milieu with increased circulating pro-inflammatory cytokines ... thereby promoting bone resorption and inhibiting bone formation, which could ultimately increase osteoporotic fracture risk."

Previous studies looking at the relationship between uric acid and bone mineral density or fractures have been limited in design and have had conflicting results, the team explained. There have not been any prospective data evaluating this.

Therefore, Paik and colleagues analyzed outcomes from the ongoing, prospective Nurses' Health Study, which started 4 decades ago. Participants responded to biennial questionnaires that requested information about lifestyle, including diet, as well as diagnoses and medications. The current analysis included 103,799 women who were enrolled as of 1990.

A total of 2,225 of the participants reported a history of gout. Those with gout were older (59.6 versus 56 years), had higher BMI (29.2 versus 25.8 kg/m2), lower physical activity (14 versus 15.5 metabolic equivalent task scores), and more often had hypertension, osteoporosis, and diabetes and to be taking thiazide diuretics.

During 22 years of follow-up that included 1,878,333 person-years, there were 2,147 incident hip fractures, and 14,382 participants had a history of gout. Among the women with gout, there were 117 hip fractures.

The risks for hip fracture were similar to those for women whose BMI was above or below 25 kg/m2 and whether or not they had diabetes. However, the risk was more pronounced in women younger than age 65 (RR 2.19, 95% CI 1.35-3.56) than in those older than 65 (RR 1.28, 95% CI 1.04-1.58, P for interaction 0.02). The association also was greater in those on thiazide diuretics (RR 1.92, 95% CI 1.37-2.70) compared with those not taking these medications (RR 1.16, 95% CI 0.92-1.48, P for interaction 0.02).

The researchers also considered whether the risks for wrist fractures were increased. This analysis included 14 years of follow-up (1,296,844 person-years), during which time there were 3,769 incident fractures of the wrist and 8,834 women who reported having been diagnosed with gout. A total of 107 wrist fractures occurred among women with gout.

Wrist fracture was not associated with gout either on an age-adjusted analysis (RR 1.07, 95% CI 0.88-1.30) or in a multivariable analysis (RR 1.12, 95% CI 0.92-1.36).

The associations with wrist fracture did not differ according to age, BMI, diabetes, or use of thiazides, the team reported.

The observation that risks were increased only for hip and not for wrist fracture indicates that the risk for fractures can differ according to the site. "While hip fracture risk increases with age and is associated with markers of poorer health and frailty, including co-morbid conditions, impaired neuromuscular function, and lower physical activity, wrist fracture does not increase with age and often occurs as a result of a fall in women with low bone mineral density who are otherwise relatively healthy and physically active with intact neuromuscular function," the researchers explained.

They also noted that further studies will be required to clarify the interactions between gout, hip fracture, and age and thiazide diuretic use.

If the risks are confirmed in other studies, it would be useful to examine the potential effects of urate-lowering treatment on fracture risk, Paik and colleagues suggested.

Limitations of the study included a lack of information on bone mineral density and a reliance on self-reporting of gout.

This research was supported by the National Institutes of Health. Some of the co-authors reported financial relationships with AstraZeneca, Lilly, Pfizer, Genentech, Bristol-Myers Squibb, and Takeda.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 09.12.2016

Primary Source

Arthritis & Rheumatology

Source Reference: Paik J, et al "Gout and risk of fracture in women: a prospective cohort study" Arthritis Rheum 2016; DOI: 10.1002/art.39852.