Background/Purpose: Prior studies suggest an association
between osteoporosis, systemic inflammation and pro-inflammatory cytokines such
as IL-1 and IL-6. Gout is a common inflammatory arthritis characterized by
hyperuricemia leading to crystallization of uric acid in joints. Several observational
studies, but not all, report a relationship between hyperuricemia and bone
mineral density (BMD). Furthermore, it is unknown whether gout has an impact on
BMD and the risk of osteoporotic fracture.

Methods: Using data from a US commercial
insurance plan (2004-13), we conducted a cohort study to evaluate the incidence
rate (IR) of any non-vertebral fracture (i.e. forearm, wrist, hip and pelvis) and
hip fracture in patients with and without gout. Gout patients were identified
with ≥2 diagnosis codes and ≥1 dispensing for a gout-related
drug. Non-gout patients were free of gout diagnosis and received no gout-related
drugs; but, the non-gout group had ≥2 physician visits for any diagnosis
and ≥1 dispensing for any prescription drugs. Non-vertebral fracture was
defined with a combination of diagnosis and procedure codes for
invasive/noninvasive treatment for fracture. The index date was the date of the
1^st dispensing of a gout-related drug for the gout group or any drug
for the non-gout after ≥1-year continuous enrollment. We excluded patients with prior fracture, malignancy, chemotherapy, ESRD,
or renal transplantation. The non-gout group was matched to the gout
group on age, sex and the index date with a 3:1 ratio. We calculated the incidence
rates (IR) of non-vertebral and hip fracture in both groups. Multivariable Cox
proportional hazards models compared separately the risk of non-vertebral and
hip fractures in patients with and without gout.  

Results:
We identified 73,202
gout and 219,606 non-gout patients, matched on age, sex, and the index date.
The mean age was 60 years and 82% were men. Among patients with baseline uric
acid levels available (n=18,176), the mean (SD) uric acid level (mg/dL) was 7.4 (2.0) in gout and 6.0 (1.4) in non-gout. Over
the mean 2-year follow-up, the IR of non-vertebral fracture per 1,000
person-years was 2.92 in gout and 2.66 in non-gout.  In both groups, the IR of non-vertebral
fracture was 3-fold higher in women than men (Table), but no significant interaction between sex and effect of
gout on fracture was noted (p=0.4). Multivariable HR adjusted for potential
risk factors for osteoporotic fracture in gout patients was 0.98 (95%CI 0.85-1.12)
for non-vertebral fracture and 0.83 (95%CI 0.65-1.07) for hip fracture. In the subgroup
analysis further adjusted for baseline serum uric acid levels, HR of
non-vertebral fracture in gout was 1.20 (95%CI 0.54-2.67).

Conclusion: In this large cohort study, gout does
not appear to be associated with an increased risk of non-vertebral or hip
fracture. Whether serum uric acid is associated with osteoporotic fracture
needs to be further studied.