Despite limited data on this current topic of interest, if compared to the vast number of publications on osteoarthritis and frailty when considered independently, and the fact both conditions have multiple parallel determinants and consequences, most available evidence points to the possible value of uncovering how frailty and osteoarthritis may interact or be associated and in what respect. In general, and in this regard, it appears fair to say a growing body of documentation indicated osteoarthritis cases may not always be obese, but in fact a proportion may be deemed frail and underweight. Moreover, those deemed to be non frail may yet develop incident osteoarthritis, and those with osteoarthritis may become frail over time. In addition, those osteoarthritis cases who succumb to frailty, as well as frail elders who develop osteoarthritis, appear to experience worse health outcomes when viewed concurrently, and compared to their individual impacts on health.

As well, current data indicate a possible bidirectional association between osteoarthritis and frailty in a sizeable proportion of older adults with interactions that stem from possible underlying health determinants such as a heightened susceptibility to oxidative stresses, systemic inflammation, adverse immune responses, polypharmacology, sleep problems, and a heightened vulnerability to stresses 43335. In particular, even if osteoarthritis cases do not appear frail at the outset, the persistent presence of unrelenting chronic pain may well be expected to induce a variety of physiological responses that may hasten the onset of a progressive state of frailty, and with this a high susceptibility to low magnitude bone stresses and ensuing injurious joint outcomes, as well as less than optimal outcomes if surgery is needed 39. As well, a combination of osteoarthritis and frailty can be expected to foster the possible onset or worsening of multiple chronic health conditions, a rapid decline in muscle strength, endurance, and muscle mass, bone mineralization and physical abilities as well as cognitive abilities 4041. However, while the importance of considering these highly deleterious possible clinical associations in the context of osteoarthritis is thus being stressed by some 12, screening alone, while useful, may not be sufficient in cases where clear frail states are not evident, for example if the older adult has a mesomorphic body frame or is in a pre-frail state but does not match criteria for detection. Indeed, frailty presence assays for example that are based solely on checklists designed to demote grip strength, walking speed, and activity parameters 33 may make it possible for the elderly adult with hand pain, who walks slowly due to joint instability or diabetes, but not frailty to be classified as frail. Alternately, an older adult with osteoporosis, who is active, and has a normal hip to waist ratio, weak lower limb muscles, but adequate grip strength, may be deemed non frail, inadvertently, but erroneously. In addition, the instruments used to classify both osteoarthritis as well as frailty may not be equally sensitive across studies as discussed by Wang et al. 13 and Pulik et al. 39. Additionally, there is a frequent lack of agreement between frailty assessment approaches 42, imperfect predictability, and limited data on community based versus hospital based samples 43. At the same time, it cannot be assumed that check lists can be readily applied in real life situations where older adults may not all be literate or have intact vision and hand writing skills, for example in the context of a 25 item frailty associated survey sent to the older adult 35. Moreover, in addition to the possible exclusion of salient older adults being examined in community based settings, for multiple reasons, including limited literacy and vision, evaluations conducted within the constraints of a research context may not truly represent the characteristics of the general population at all adequately and may well underestimate or overestimate the importance of frailty in the midst of osteoarthritis disability, in particular, if such efforts fail to address the subject’s overall medical history, and perceived self-efficacy for managing their health, among other factors .

Nonetheless, and until more robust research is conducted, it is concluded that attempts to identify frailty or frailty correlates in clinical osteoarthritis contexts as optimally and accurately as possible, coupled with subsequent efforts towards addressing any preventable and observed probable determinants of frailty at the earliest point in time may not only prove efficacious for offsetting frailty, but quite helpful for averting those osteoarthritis mediators such as falls injuries and others, as well as surgeries due to poor nutrition, depression, excess disability and a failure to address modifiable health attributes such as bone mass 4445. It may also be a wise approach given that frailty as assessed by the Frailty Staging System was found to significantly predict mortality in both osteoarthritis as well as disease free cases over time, but more so in those with osteoarthritis 4647. Those who might be at most risk and might be targeted accordingly are likely to be those who are depressed, those taking multiple medicines, those with chronic conditions, high pain levels, and low levels of education 10114849.

In regards to the question of whether cases with osteoarthritis can not only exhibit frailty, but whether those who have osteoarthritis, and do not appear to fit the criteria for frailty at the outset can become frail, a revealing study by Bindawas et al. 51 who examined the longitudinal association between knee pain, the most symptom of knee joint osteoarthritis and frailty, found that after adjusting for age, sex, race, education, marital status, smoking status, comorbidities, and body mass index, unilateral knee pain at baseline was associated with an increased 1.14 odds of developing pre frailty and a 1.89 odds ratio for developing frailty. Bilateral knee pain at baseline was also associated with an increased risk of pre frailty and frailty over time in comparison to those with no knee pain. It was concluded that knee pain (particularly bilateral knee pain) is associated with an increased risk of developing pre frailty and frailty over time. However, although data from five clinical venues located in the United States and 3,053 non frail participants aged 45-79 years were studied to enhance generalizability of the findings, the subjects studied did not however appear to have definitive osteoarthritis at baseline, hence the link to this disease could not be verified.

Veronese et al. 29 however, concluded that pain does appear to increase the risk of developing frailty in older adults who are diagnosed as having osteoarthritis. To this end this group conducted a population-based prospective cohort study with a follow-up of 4.4 years and that included 1,775 older men and women with osteoarthritis enrolled in another study. Results of a fully-adjusted logistic regression analysis demonstrated that lower limb osteoarthritis-related pain was associated with an increased risk of developing frailty compared with people with osteoarthritis and no pain. Hence, pain related to osteoarthritis appeared to be a highly salient factor influencing the relationship between the presence of lower limb osteoarthritis and the development of frailty.

In addition to the probable highly relevant data reported above, McAlindon et al. 52 in addressing the question of whether frailty can lead to osteoarthritis further note that in their opinion the presence of skeletal fragility, a widespread aging correlate, can possibly account for findings of increasing severity of the severely impairing condition known as erosive hand osteoarthritis. In this regard, frailty also appears to predict worse outcomes of reconstructive surgery for advanced osteoarthritis, possibly due to its negative impact on both bone and muscle. Wang et al. 13 for example who undertook a prospective, observational, pilot study of patients 65 years or older awaiting elective knee or hip replacement surgery for disabling arthritis found between 5% and 10% of these patients were deemed frail and hence at risk of possible adverse outcomes. Pulik et al. 39 support this idea and found those deemed frail before surgery had poorer outcomes than the non frail. As well, frailty delayed neuro cognitive recovery in a similar surgical sample 44.

In terms of further frailty implications in the context of osteoarthritis, Blanco-Reina et al. 48 who examined the prevalence of frailty among 582 older community dwelling Spanish adults and who found signs of frailty in 24.1% of the study sample named osteoarticular pathology as one of the key determinants in this regard. An even higher frailty rate was observed by Sharma et al. 10 who examined the presence of frailty among older adults aged ≥80 years, where the presence of poor physical performance ability, depression, and chronic joint pain, as occurs in osteoarthritis were key predictors.

Lee et al. 11 who attempted to examine the nature of frailty transitions and their associated factors among 3018 Chinese community-living adults 65 years or older found that at baseline 850 (48.7%) men and 884 (52.6%) women were pre frail, and that while among these cases deemed at risk for frailty, including 23.4% men and 26.6% women these cases tended to improve after 2 years; while 11.1% of men and 6.6% of women tended to worsen. Hospitalizations, older age, previous stroke, lower cognition, and osteoarthritis were listed as being among the key risk factors for any observed decline among the pre frail participants.

Trevisan et al. 53 who similarly elected to investigate frailty state transitions in a cohort of older Italian adults in the context of a population-based longitudinal study with mean follow-up of 4.4 years, found 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. It was concluded that frailty is a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status. As per Zhobina et al. 54 these targets might include efforts to prevent osteoporosis, sarcopenia, and the presence of joint hypomobility, a common functional feature of osteoarthritis pathology.

Pérez-Sousa et al. 34 found that along with probable sarcopenia, individuals who are physically inactive, have diabetes, arthritis, or osteoarthritis do tend to have a higher prevalence of probable sarcopenia that could foster frailty and lower the threshold to injury and excess joint destruction. It could also render efforts to curtail osteoarthritis pain more challenging as certain anti inflammatory drugs have been cited as harmful in the presence of frailty 55. Pre existing frailty may also impact knee joint replacement surgeries negatively and significantly as far as impacting rehabilitation trajectories, prolonging the use of walking aids, heightening the risk of post operative complications and surgical efficacy 56.

Ritt et al. 38 noted those patients of theirs that were deemed to be frail also had an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. This association between frailty and adverse clinical was independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and was found to occur as well in younger patients, a fact not often recognized. At the same time, other data imply more attention to offset frailty at all ages is not only desirable, but essential in consideration of its impact on older adults. This is because frailty is not only found to significantly predict a high risk for fracturing one or more bones 2631, but severe insomnia symptoms 35, and increased mortality rates in both subjects with and without osteoarthritis, but especially those with osteoarthritis 47262831. Factors to consider here other than older age are being female, obese, having cardiovascular disease, osteoarthritis, a loss of vision, having lower education levels, low levels of self-efficacy and physical performance, plus cognitive impairments, poor health perceptions, hypovitaminosis D, hyperuricemia, and polypharmacy 5357.

Lee et al. 11 further imply that among the factors that foster frailty are the presence of diabetes, and a previous cancer history, the presence of any chronic lung disease, and stroke. According to de Villiers 58 frailty is a state of ‘weakness’ associated with cognitive impairment, depression, social isolation, multiple health issues such as osteoarthritis, medication side-effects, low levels of physical activity, and a high tendency to falls, functional declines, and increasing frailty. In accord with these aforementioned findings, Li et al. 56 argued in favour of early recognition and identification of frailty in the context of any rehabilitation clinic or hospital and that might help physicians to provide appropriate counselling to at risk patients and their families. Song et al. 19 further suggest interventions that promote reductions in sedentary behaviors in addition to increases in physical activity may be especially helpful for decreasing physical frailty onset and progression, as may efforts to increase energy expenditure, and to avoid restrictive diets 58.

A summary of key observations extracted from the literature that may offer some important clinical insights in this regard is listed below in Table 1.

In sum, as identified by Salaffi et al. 63, frailty represents an important construct that can be avoided, or at least needs to be identified by those who seek to reduce the vulnerability of older adults to excessive degrees of suffering and highly unfavourable health outcomes, especially among those challenged by painful osteoarthritis of one or more joints. This argument accords with that of O Brien et al. 18 who argued that frailty may not only drive osteoarthritis development by creating an inflammatory environment that can interfere with normal tissue health, but also high disability rates. The molecular and biochemical changes associated with prevailing or emergent osteoarthritis may in turn exacerbate or foster frailty among those exhibiting pre frailty as well as non frail states, thus producing an inexorable deterioration of the affected osteoarthritic joint, and possible high frequency of falls and depression 45.

In this regard, research conducted by Wanaratna et al. 61 found physical frailty as well as the presence of cognitive frailty to heighten the risk for adverse outcomes among older people in general, as well as those diagnosed as having osteoarthritis of the knee and who are living in the community, and who are presumably healthier than those residing in nursing homes who have been less well represented in the available literature. In fact, increasing evidence shows frailty is not uncommon among older community dwelling adults who have advanced end stage osteoarthritis requiring surgery, although the extent to which frailty heightens surgical risk is implied but not well examined 64 and may depend on the adoption of healthy lifestyles and life affirming environments. As per Wanaranta et al. 61 the prevalence of frailty and pre-frailty is indeed found to be quite high in cases with knee osteoarthritis, regardless of age, especially among those suffering from malnutrition, and those exhibiting excess functional dependence, and cognitive frailty. It is also associated with the presence of co morbidity 60 and less than optimal outcomes among elders deemed frail and who undergo primary hip joint replacement surgery 39, as well being associated with the presence of severe pain 1765, persistent signs of local or systemic inflammation 17, excess sedentary practices 19, as well as a lower than desirable muscle mass, plus a higher muscle fat mass 6667.