allopurinol and Hip-Fractures

Allopurinol reduces oxidative stress and interacts with purinergic signalling systems important in bone metabolism and muscle function. We assessed whether allopurinol use was associated with a reduced incidence of hip fracture in older people.. Analysis of prospective, routinely-collected health and social care data on patients undergoing health and social work assessment in a single geographical area over a 12year period. Exposure to allopurinol was derived from linked community prescribing data, and hospitalisation for hip fracture and comorbid disease was derived from linked hospitalisation data. Fine and Gray modelling was used to model time to hip fracture accounting for the competing risk of death, incorporating previous use of allopurinol, cumulative exposure to allopurinol as a time dependent variable, and covariate adjustments.. 17,308 patients were alive at the time of first social work assessment without previous hip fracture; the mean age was 73years. 10,171 (59%) were female, and 1155 (8%) had at least one exposure to allopurinol. 618 (3.6%) sustained a hip fracture, and 4226 (24%) died during a mean follow-up of 7.2years. In fully-adjusted analyses, each year of allopurinol exposure conferred a hazard ratio of 1.01 (95% CI 0.99, 1.02; p=0.37) for hip fracture and 1.00 (0.99, 1.01; p=0.47) for death. Previous use of allopurinol conferred a hazard ratio of 0.76 (0.45, 1.26; p=0.28) for hip fracture and 1.13 (0.99, 1.29; p=0.07) for death.. Greater cumulative use of allopurinol was not associated with a reduced risk of hip fracture or death in this cohort.

Topics: Aged; Allopurinol; Female; Hip Fractures; Humans; Male; Proportional Hazards Models; Time Factors

Using a Danish Register cohort of 86,039 adult new allopurinol users and propensity score matched controls, we found that gout requiring allopurinol prescription was associated with an increased fracture risk.. Gout, an acute inflammatory arthritis, is common and associated with elevated serum urate, obesity and high alcohol consumption. The mainstay of therapy is the urate-lowering agent, allopurinol. Here, we report the relationship between allopurinol prescription and fracture in a large registry population.. We established a Danish Register cohort of 86,039 adult cases (new allopurinol users) and 86,039 age, sex and propensity score matched controls (not exposed to allopurinol or with a gout diagnosis), with no diagnosis of malignancy in the year prior.. We found a modest adjusted effect of allopurinol prescription on major osteoporotic fractures (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.05-1.14, p = 0.04) and on hip fractures (HR 1.07, 95 % CI 1.11-1.14, p < 0.001), robust to adjustment for confounding factors (age, sex, comorbidity, medication use). Associations were stronger in men than women, and among incident allopurinol users whose gout diagnosis had been confirmed by at least one hospital contact. Prespecified subanalyses by filled dose of allopurinol (mg/day in first year of prescription) showed increased hip and major fracture risk in women in the highest allopurinol dose grouping only, while a less strong dose effect was evident for fracture rates in men.. Gouty arthritis requiring allopurinol is associated with an excess risk of major or hip fracture, with an allopurinol dose effect evident in women such that women taking the highest doses of allopurinol--suggestive of more severe disease--were at increased risk relative to women taking lower doses.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Denmark; Female; Gout; Gout Suppressants; Hip Fractures; Humans; Male; Matched-Pair Analysis; Middle Aged; Osteoporotic Fractures; Propensity Score; Proportional Hazards Models; Registries; Risk Factors; Uric Acid

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD.

Topics: Aged; Allopurinol; Bone Density; Cohort Studies; Gout; Hip Fractures; Humans; Incidence; Male; Osteoporotic Fractures; United States; Uric Acid