Both areal and volumetric bone mineral density in our patient population was significantly lower than the age and sex-matched controls. This finding is in agreement with a number of studies that have reported PsA patients with an increased risk of low areal bone mineral density [22–27]. But simultaneously is in disagreement with another series of studies that did not report low areal BMD [28–33]. This dichotomy may be due to the non-consistent comparison groups and reported outcomes. Our finding of FN areal BMD significantly correlating with disease duration supports similar previous findings [24, 31, 34].
BMD measured by pQCT have been reported previously by Kocijan et al [35]. Kocijan et al reported that trabecular and not cortical density was significantly lower in the patient population as compared to the controls, this finding is in contrast to our results of decreased trabecular and cortical density in the patient population. A probable explanation for this discrepancy may be due to the fact that our patient cohort is older, with longer psoriasis and arthritis disease duration. The present study is the first where areal BMD has been compared to volumetric BMD in PsA patients, with statistically significant correlation between the two methodologies. This finding is in tally with 2 other studies in patients with inflammatory rheumatic disease [13, 14].
We observed a significantly increased 10-year probability of both major and hip osteoporotic fractures as assessed by the FRAX tool in the studied Hungarian patients with psoriatic arthritis. Probability of fragility fractures has not been reported previously in PsA patients using the FRAX tool. Our probability findings are in concordance with findings where osteoporotic fractures were studied as primary endpoints, reporting higher odds of diagnosis with pathological fractures and elevated risk of all fractures [22, 36, 37]. A cross-sectional study from Spain reported increased prevalence of fragility fractures in postmenopausal PsA patients [28]. A Brazilian study reported longer disease duration as predictor of low-impact fractures [26]. Nonetheless, an Italian study reported no difference in the prevalence of fragility fractures between cases and controls [38].
Beside known predictors of the 10-year probability of fragility fractures, i.e., age and BMD, our findings suggest that in PsA, severe disease activity as assessed by DAS28 is also a noteworthy risk factor.
FRAX assessment and DR volumetric BMD measurement are excellent alternatives when FN BMD cannot be measured, as in our study where one patient had total bilateral hip replacement.
Although patients identified as being osteoporotic with FN areal BMD measurement were also classified as osteoporotic with DR volumetric BMD measurement, volumetric measurements identified a significantly greater number of patients with low bone mass (34% vs. 88%, p<0.001). Although manufacturer provided German reference population is used to derive the T-score with both methodologies, the absence of agreement has also been reported by Marshall et al [39].
Fracture risk assessment using the FRAX tool identified more patients deserving anti-osteoporosis treatment as compared to FN areal BMD assessment (n = 8 vs. n = 6). Patients with major osteoporotic or hip fracture probability in the intervention range, i.e, ≥20% (n = 8) and ≥3% (n = 1), respectively, were also osteoporotic when assessed for DR volumetric BMD, nonetheless, a wide discrepancy was noticed as a significant proportion of the cohort with non-intervention level FRAX probability was identified as osteoporotic (n = 28, 24%). The FRAX tool offers optional inclusion of FN areal BMD and its clinical utility in identification of those at increased risk of fragility fractures may be improved were volumetric BMD values and psoriatic arthritis, as a secondary risk factor, also facilitated in the calculation of fracture probability.
The FRAX tool is designed to assess those between 40 and 90 years of age, given this inherent limitation the fracture probability of the young cannot be assessed. Among those under 40 years of age (n = 18), areal FN BMD assessment identified 3 (17%) and DR volumetric BMD examination identified 16 (89%) psoriatic arthritis patient with low bone density (T Score ≤ -1.0). Our observation suggests that volumetric BMD assessment better identifies those at increased fracture probability, and offers opportunity to initiate fracture risk reduction intervention promptly at a younger age. The true burden to osteoporosis may be underestimated with areal BMD measurement alone.
The Hungarian National Healthcare System subsidises antiosteoporotic therapy for those with an osteoporotic T score, based on the WHO classification (T Score ≤-2.5), or with FRAX probability of more than 3% and 20% for hip and major osteoporotic fracture, respectively. Our results suggests that a number of osteoporotic and osteopenic patients deserving fracture risk reducing intervention are missed using areal BMD measurement alone, and as such FRAX assessment.
As compared to the control groups, the studied biochemical markers of bone turnover were significantly elevated suggesting a high bone turnover in the PsA population. This finding is supported by one previous study [40]. Grisar et al reported that CTx levels were significantly higher in the PsA group as compared to the healthy controls [29]. Szentpetery et al reported correlation between the studied bone markers and hand BMD [41]. Borman et al reported correlation between CTx and duration of arthritis and no difference in marker levels comparing patients with and without arthritis [27]. Nonetheless, in our study we found no correlation between the studied parameters and bone markers. The inconsistency in bone marker results in the numerous studies published has been summarized in a review by Jadon et al [42].
Our finding of high hypovitaminosis D prevalence is in concordance with results from quite a few previous studies [40, 43–45]. Although a study has reported that there is no difference in vitamin D levels between patients suffering from psoriasis with and without arthritis, correlation between disease activity and vitamin D levels has also been reported inconsistently [11, 40]. A probable predisposition for hypovitaminosis D in the PsA cohort may be due to the debilitating nature of their condition, and as such, they may not involve in physical activity that may be naturally assumed for a healthy age- and sex-matched counterpart; in addition, patients may shy away from outdoor activity given the psychological burden of their skin condition.
Although not supported by correlation analysis in our study cohort, hypovitaminosis D, high bone turnover and low bone mass may contribute to the increased fragility fracture probability in this population.
There are limitations to our study. Due to difficulties in getting access to the local population register and no commercially available population registers, we employed a method where recruitment of healthy volunteers may have been biased. Validation of our results is deemed mandatory optimally with a substantially larger cohort.
A higher number of study participant could have improved the statistical power of our analyses, nonetheless, we report a high 10-year probability of fragility fractures along with an increased prevalence of hypovitaminosis D in a PsA cohort complemented with low bone mass and high bone turnover; furthermore, the comparison to a systematically selected healthy age- and gender-matched population discards the effect of confounding risk factors.
Although warranting validation, the clinical utility of volumetric BMD examination complemented with traditional DEXA-based areal BMD measurement and FRAX assessment, are readily applicable in the PsA patient population and serve as an inexpensive tool in identifying those at increase fracture risk. Prompt identification, treatment and follow-up of patients at risk would help in reducing the burden of fragility fractures in the PsA patient population.