Our results indicate that 68.8% of people with HKOA in Portugal live with UPL, which is higher than the prevalence of UPL in Mexico (53%) [27], the Survey of Osteoarthritis Real World Therapies (SORT) cohort from six European countries (54%) [10], and a sample of Portuguese people with knee OA included in the SORT cohort (51%) [28]. All three of these earlier studies included people who were ≥ 50 years old, possibly excluding younger patients with early OA, and who took analgesics regularly, which may explain why we found a higher prevalence of UPL in the present study.Our study included a representative sample of the Portuguese population who live in the community, suggesting that offered interventions do not meet the need for pain control for more than two-thirds of the Portuguese HKOA population.
We found that people with UPL had lower education levels than people with MPL. This finding is consistent with previous literature reporting that low education is associated with more severe OA symptoms, is a social determinant of unhealthy lifestyles and multimorbidity [27, 29], is a determinant of lack of access to and delay in seeking healthcare [30], and is associated with increased pain intensity over time [31].
The multivariable model showed that female sex, overweight and obesity, and multimorbidity were associated with UPL, similar to the results of the SORT study [10]. In our study being female was associated with higher OA-related pain levels, but gender differences on pain intensity in HKOA remain unclear in the literature. Data from quantitative sensory testing in people with knee OA has shown that women have greater sensitivity to pain but no sex differences were found in clinical pain. These authors suggested that women have an enhanced central pain sensitivity [30]. More recently, Mun et al. (2020) concluded that women with knee OA have a greater interleukin 6 activation when compared to men, after laboratory quantitative sensory testing. These authors concluded that this enhanced inflammatory reactivity in women may contribute to exacerbation or maintenance of symptoms [31].
Other factors like psychosocial and genetic factors showed inconsistent gender differences and pain severity [32] [33].. Also, a systematic review of progression phenotypes among people with OA shows that overweight or obesity is a major factor in the progression of OA and is associated with worsening of pain, loss of physical function, and structural deterioration over time [34].
Additionally, our results show that having multimorbidity was associated with UPL. Multimorbidity is associated with chronic pain in a cumulative manner [35] and is related to pain intensity in people with HKOA [36]. People with multimorbidity have a higher likelihood of walking impairments, which can contribute to a worsening of OA and other chronic conditions that occurswith an additional consequence of psychological distress [35, 36].
We found that UPL was negatively associated with performance in ADL and QoL. Previous research reveals that within the OA population, pain severity explains most of the variability in disability and QoL [37]. High pain severity may lead to fear of movement and/or avoidance behaviors, resulting in physical inactivity and less participation in social activities and leads to greater physical disability, psychological distress, and reduced QoL [38].
The sensitivity analysis did not show differences when separating participants with hip OA and with knee OA. This suggests that similar factors were associated with UPL in people with OA in these two joints, separately or together. However, due to the small sample size of participants with hip OA, we were not able to perform multivariable analysis for anxiety and depression symptoms.International clinical practice guidelines recommend that topical NSAIDs be considered before oral NSAIDs consistentwith the least systemic exposure principle, and oral NSAIDs are strongly recommended at the lowest possible dose [39]. Given the limited efficacy of paracetamol and its potentially harmful secondary effects, it is only conditionally recommended for people with OA [39]. Although tramadol is conditionally recommended, non-tramadol opioids are not recommended for the management of pain in people with OA. Tramadol and non-tramadol opioids can be used only when alternatives have been exhausted. Glucosamine is strongly not recommended for people with HKOA [39]. In the present study, oral NSAIDs were the most used medication followed by analgesics/antipyretic medication, whereas topical NSAIDs were the least used pharmacological modality. People with UPL regularly took more medication for pain relief, namely NSAIDS, opioids, and analgesics, specifically paracetamol, than people with MPL, consistent with the results of the SORT study [10]. A cohort study from the Netherlands also shows pain severity is positively related to analgesic intake; however, the authors concluded that most reasons for analgesic prescription are unknown [40].
Even though no temporal relationships can be drawn from a cross-sectional design, this study reveals that a higher proportion of people who took daily pain medication in the previous month had UPL. Additionally, our results suggest that medication is taken by a much lower proportion of people with OA in Portugal than in other European countries [12]. (12)In Europe, medication use seems to be highly variable across countries. Data from five countries included in the National Health and Wellness Survey (n = 37,650), reveal that the minimum and maximum proportions of overall pain medication intake by people with OA was 22% in Germany and 53.2% in Spain. Specifically, NSAID’s were at minimum by 46,5% of people with OA in France and at maximum by 81.9% in Germany; Paracetamol was not used by any participants of Germany, but by 6% of participants from Spain. Opioids were used by 1.8% in Italy at minimum and by 54.5% at maximum of people with HKOA in France. These proportions of medication use were much higher than the ones seen in our findings probably because medication intake was asked as “medication used at the moment” [12] rather than daily use of medication in the previous month, as in our study. Similarly, our findings reveal that NSAID’s are the medication most used by people with HKOA. In other European countries opioids are the second most used pain medication, contrarily to our study (used similarly to analgesics). These findings may suggest that opioids are less prescribed in Portugal than in other countries. However, data from the general population reveal that the prescription of opioids in Portugal has increased by 1.5-fold between 2013 and 2017 [41].
Although randomized controlled trials show that analgesic drugs and other recommended interventions effectively manage pain in individuals with OA, adherence to medication and healthy lifestyle behaviors are a real-world concern that prevent the optimization of pain control in this population. A qualitative meta-ethnographic study points out that factors such as the severity of pain, perceived effect of medication, fear related to side effects, acceptability of dose regimens, education and knowledge about OA and the medication regimen, self-efficacy, and locus of control over OA influence medication adherence [42].
Regarding conservative non-pharmacological therapies used by people with HKOA, we found that < 20% of people with UPL underwent physiotherapy in the last 12 months or regularly exercised. These values are much lower than other European countries. For example, the proportion of people with OA in national cohorts that used physiotherapy in a 12-month time frame was 53.1% in Germany [43] and 32% in the UK [44].
Crrent clinical guidelines recommend physiotherapy and exercise as first-line treatments. Exercise should be maintained during the progression of the disease for pain management purposes [45, 46]. Although, similarly to our results, current literature suggests that exercise and physiotherapy, as part of core non-pharmacological treatments, are uptake by < 50% of people with HKOA [47, 48]. Additionally, healthcare interventions seems to be symptom-driven and segmented [49] centered on pharmacological [47, 48] and surgical options [50]. On the other hand, lack of long-term adherence to behavior-dependent interventions, like exercise has been pointed out as an explanation for poor long-term outcomes in people with HKOA [51, 52]. Therefore, interventions for the management of HKOA should also target behavior changethrough strategies that optimize motivation and overcome barriers of adherence [53].
Limitations
Our study has several limitations that should be considered. A large proportion of participants included in the first phase of the study and invited for the second phase did not show up in the rheumatologist appointment. Therefore, we should hypothesize a selection bias, since the subjects who were willing to participate in the appointment might be the most severe cases.
Due to its cross-sectional design, no cause-effect relationships can be established between UPL and sociodemographic, lifestyle, and health-related variables. Additionally, identification of variables with direct and indirect effect on the outcome is not possible with this study design and was not accounted in the regression models [54]. Also, giving the cross-sectional design of the study, the variables related with the use of therapies were considered only to describe and compare UPL/MPL subgroups and no associations with the outcome variables were explored. Also, estimation of the proportion of people with UPL in the Portuguese population using sample weights is not free from error, although sample weights are recommended for all statistical analyses using complex samples data [55].
[1, 43](58)We used the validated cut-off by Zelman et al. (2003), to define people with UPL and MPL. However, in this validation study the eligible criteria included people with HKOA that have at least 1 year pain duration, that have a daily use of some form of analgesic and that reported average daily pain of 4 at least in the 11-point NPRS [19]. Notwithstanding, the cut-off “5” was previously validated in other populations as pain intensity that interferes with function and QoL - musculoskeletal pain in general [56], in patients with knee OA [10] and in those with HKOA waiting for surgery [57]. In this late study the authors concluded that the interference of pain in function (using the same cut-off) was independent from pain duration. Therefore, we cautiously believe that this cut-off is valid also in the population of our study.
We asked participants about their use of “regular medication”. However, as people with OA often use analgesic medication sporadically for pain flares rather than daily, our results may underestimate the proportion of people that use medication for symptomatic control. On the other hand, we did not control for other pain conditions like fibromyalgia or widespread pain syndromes, pain duration or pain frequency (e.g. daily or constant pain) that may increase the intake of medication. Also, as physiotherapy attendance in the last 12 months was self-reported, we acknowledge the possibility that memory bias may compromise the accuracy of our results. Additionally, we did not investigate the reason for medication use or physiotherapy.
Surgery procedure was not specified, and this variable (surgery - yes/no) was not related to a specific time frame. Additionally, since the causes of surgery are not known our results were purposively descriptive and no hypothesis can be drawn. “Regular exercise” was self-reported by participants and did not consider the precise amount and intensity. Hence, our data may overestimate the proportion of people who exercised. Moreover, pain intensity is multifactorial [38], and several potentially important factors were not considered in the analysis, such as fear avoidance beliefs, catastrophizing, or coping strategies.
The analyzed data were collected in 2011–2013, but due to few specific strategies directed to RMDs in the last decade in Portugal, we cautiously believe that the current management of OA does not differ from that reflected in this study.
Strengths and implications
This is the first population-based study in Portugal analyzing outcomes of current interventions offered to community-dwelling people with HKOA. The results of this study raise concerns regarding important factors that should be further explored in future research and addressed in national health policies to optimize the outcomes of people with HKOA, namely:
1) The high proportion of people with UPL, suggest a poor control of pain levels in people with HKOA;
2) The high proportion of people with UPL who use pharmacological and non-pharmacological therapiesmay indicate that pain management is suboptimal;
3) Besides the low proportion of people who use therapy, the interventions offered do not seem to be aligned with international recommendations [39, 45] considering the small proportion of people who underwent physiotherapy, exercised, and used pain medication and the large proportion of people who were overweight or obese.