Psoriatic Disease Tied to Elevated Fracture Risk

Diana Phillips

January 24, 2017

Adults with severe psoriasis are more than twice as likely as their peers in the general population to experience vertebral fractures, researchers report in a study published online January 16 in Annals of Rheumatic Disease. Further, all patients with psoriasis and psoriatic arthritis (PsA) are at increased risk for sustaining a fracture of any type.

Previous studies have suggested a relationship between psoriasis and PsA and osteoporosis/osteopenia, but this is one of the first studies to evaluate the risk for incident facture in patients with these conditions, write Alexis Ogdie, MD, assistant professor of medicine in the Division of Rheumatology at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and colleagues.

Using data from The Health Improvement Network (THIN) in the United Kingdom collected between 1994 and January 2014, the researchers compared the incidence of fracture in patients aged 18 to 89 years diagnosed with PsA (n = 9788), mild psoriasis (n = 149,809), or severe psoriasis (n = 8514) with that in matched controls (n = 821,834) from the general population and from a population of patients with rheumatoid arthritis (RA; n = 39,306). RA is a known risk factor for osteoporosis, which may share inflammatory pathways with psoriatic disease.

For the study, patients with PsA, psoriasis, and rheumatoid arthritis were identified by the presence of at least one diagnostic code consistent with these conditions. Severe psoriasis was defined by the presence of a diagnostic code for psoriasis and a code for treatment with phototherapy or systemic medication.

Relative to the control population, patients with PsA and psoriasis had an increased prevalence of risk factors for osteoporosis and fracture, including diabetes, alcohol abuse, smoking, depression, antidepressant use, corticosteroids, methotrexate and cyclosporine, the authors report.

However, even after adjustment for these risk factors, patients with severe psoriasis had a 123% greater risk for vertebral fracture (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.54 - 3.22) compared with patients in the control group. In addition, they had an increased risk for all fractures (HR, 1.26; 95% CI 1.15 - 1.39) and hip fractures (HR, 1.21; 95% CI, 0.88 - 1.66).

Among patients with mild psoriasis, the respective increased risks for any fracture, hip fracture, or vertebral fracture were 7% (HR, 1.07; 95% CI, 1.05 - 1.10), 13% (HR, 1.13; 95% CI, 1.04 - 1.22), and 17% (HR, 1.17; 95% CI, 1.03 - 1.33).

Similarly, the increased risk among patients with PsA were 16% (HR, 1.16; 95% CI, 1.06 - 1.27), 17% (HR, 1.17; 95% CI, 0.86 - 1.59), and 7% (HR, 1.07; 95% CI, 0.66 - 1.72) for any fracture, hip fracture, or vertebral fracture, respectively.

Although the incidence of hip fracture "was elevated in both psoriasis groups, it was only statistically significant in patients with mild psoriasis relative to matched controls after adjusting for risk factors for [osteoporosis]," the authors note.

By comparison, patients with RA were 23% more likely (HR, 1.23; 95% CI, 1.18 - 1.28) to have experienced any fracture compared with the general population. This finding is similar to those reported in previous studies of patients with rheumatoid arthritis, and, as such, the authors note, "provides validity to the results."

Mixed Results in Other Studies

Although the findings of the current investigation are consistent with those of earlier studies that showed an increased prevalence of osteoporosis in patients with PsA and a higher prevalence of osteopenia among patients with psoriasis, the new results appear to conflict with those reported recently by investigators with the population-based HUNT study from Norway.

In that study, the researchers found no increased risk for forearm or hip fracture in nearly 3000 patients with self-reported psoriasis, nor did they observe reduced bone mineral density T-scores or a higher prevalence of osteoporosis, based on an analysis of hospital-derived fracture data from 1995 to 2013 linked to psoriasis information, bone mineral density measures, and lifestyle factors.

Differences in study design likely account for the different outcomes, according to Dr Ogdie. The HUNT study "had a pretty small number of patients with psoriasis and was looking at very rare outcomes overall, particularly when only a third of patients were over 60," she told Medscape Medical News. "Hip fracture is pretty uncommon under the age of 60. Our unadjusted numbers for hip fracture are similar to their hip fracture unadjusted rates, but after adjusting for age and sex, the hazard ratio was pretty significantly increased for patients with severe psoriasis. This was attenuated when we accounted for other risk factors."

In addition, the HUNT cohort was based on patient-reported psoriasis, while the current investigation relied on physician diagnoses. "That may mean that the cohorts are slightly different," Dr Ogdie said. "It's possible we're capturing a group of patients with slightly more severe disease and they have a milder group — for example, patients that wouldn't be picked up by the general practitioner."

Reliance on THIN as the data source for the current investigation did impose some limitations on the current study. Specifically, "disease manifestations, disease activity and use of biological DMARDs [disease-modifying antirheumatic drugs] are not available in THIN, and therefore we were unable to directly examine their effects on risk of [osteoporosis] and fracture," the authors explain. "We were also unable to account for some lifestyle factors such as degree of immobility or laboratory parameters such as vitamin D."

Despite these limitations, the increased risk for fractures associated with psoriasis and PsA in the current study suggests that these patients should be counseled about the possible relationship and receive appropriate screening and management for osteoporosis, the authors write.

Dr. M. Elaine Husni, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at Cleveland Clinic in Ohio, agrees. Despite some contradictory findings, "there is strong evidence linking PsA and psoriasis to decreased bone mineral density and bone loss," she said in an interview with Medscape Medical News. She suggests that clinicians should have a "high index of suspicion" for osteoporosis in these patients and plan screening and management accordingly.

For example, "in our clinic, we measure bone density in postmenopausal women and men older than 50 who have PsA, and we check it in younger patients who have additional risk factors, such as steroid use," Dr Husni said. Patients with normal bone density are advised to take calcium and vitamin D, while those with bone loss and other fracture risk factors may be started on medication.

Study authors are variously supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and a Veterans Affairs Clinical Science Research & Development Career Development Award. Funds to extract the data relevant for this cohort study were provided by the Rheumatology Research Foundation Preceptorship Award. The study authors disclosed financial relationships with multiple interests, including Pfizer, Novartis, AbbVie, Astra Zeneca, Celgene, Coherus, Eli Lilly, Jansenn Biologics, Sanofi, Merck, Endo, Valeant and Eli Lilly. Dr Husni has received support from the National Psoriasis Foundation and Arthritis National Research Foundation and has served on advisory boards for UCB, Amgen, Novartis, Eli Lilly, Bristol-Myers Squibb, and AbbVie.

Ann Rheum Dis. Published online January 16, 2017. Abstract

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