Fall-related risk factors and osteoporosis in women with rheumatoid arthritis

H. Kaz Kaz1, D. Johnson1,2, S. Kerry3, U. Chinappen2, K. Tweed1 and S. Patel1,2

1 Department of Medicine and Rheumatology, St Helier Hospital, Carshalton, 2 Osteoporosis Unit, St George's Hospital and 3 Department of Community Health Sciences, St George's Hospital Medical School, London, UK

Correspondence to: S. Patel, Department of Rheumatology, St Helier Hospital, Carshalton SM5 1AA, UK. E-mail: Sanjeev.Patel{at}epsom-sthelier.nhs.uk


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Rheumatoid arthritis (RA) is associated with an increased risk of osteoporotic fractures. Whilst numerous studies have demonstrated low bone density in RA, few studies have examined the risk of falling, which is another major contributor to the pathogenesis of fractures (particularly hip fractures).

Objectives. The aim of this study was to see if fall risk is increased in women with RA, define high-risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk.

Methods. We performed a case–control study of older women with RA (n = 103) compared with women without RA referred for open access bone densitometry (n = 203). We measured bone density using dual-energy X-ray absorptiometry and fall risk factors (visual acuity, ability to perform standups, and heel–toe walking).

Results. More women with RA gave a history of a previous fall compared with controls (54 vs 44%), although this was just short of being statistically significant (difference 10%, 95% CI –2 to 22). Women with RA were more likely to have abnormal heel–toe walking and inability to perform standups compared with controls (P<0.001); however, visual acuity was similar between cases and controls. Femoral neck osteoporosis was found in 31% and increased fall risk in 68% of women with RA. Women with RA who underperformed in heel–toe walking and were unable to do standups had significantly higher ESR, Health Assessment Questionnaire score and tender joint count. RA symptoms/signs localized to the knees and ankles were more likely to be associated with the presence of fall risk factors.

Conclusions. Fall-related risk factors predictive of hip fracture are common in women with RA. Fall risk needs to be considered when RA patients are being treated for osteoporosis and further work needs to be done to help reduce the risk of falling and fracture in women with RA.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Osteoporotic hip fractures are common and cause significant morbidity and mortality. Rheumatoid arthritis (RA) is also a common disease and is associated with doubling of the rate of hip fracture compared with individuals without RA [1–4]. This is in part due to patients with RA having lower bone density at the hip compared with aged-matched non-rheumatoid controls. However, the risk of hip fracture occurring in an individual is determined by both hip bone density and the risk of falling [5, 6]. Although studies have been carried out of hip bone density in RA patients, there are no studies of fall risk and falling. The risk of falls may be higher in RA patients because of lower limb joint disease and muscle weakness (due to disuse and steroids). Visual acuity could also be reduced in steroid-treated patients due to cataract formation. As falls are important in the pathogenesis of hip fractures, this important mechanism of hip fracture may be being overlooked in RA patients. Certainly fear of falling is very common in RA patients, a recent study of 570 patients over the age of 50 yr demonstrating that 50% were concerned about falling [7].

In this study we investigate whether fall risk is increased in women with RA, define high risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Following ethical approval from our local ethics committee, we performed a case–control study. Cases were consenting women with RA aged 65 and over who fulfilled American College of Rheumatology 1987 criteria for RA and managed in the Department of Rheumatology at St Helier Hospital. Controls were women aged 65 and over living in the community who were referred by general practitioners to the open access bone densitometry service based in the Osteoporosis Unit at St George's Hospital over an 18-month period according to established referral criteria [8]. We excluded women from the control group if they had RA or other diseases causing bone abnormalities (e.g. chronic renal failure, chronic liver diseases, hyperparathyroidism, hyperthyroidism or malabsorption), or were taking steroids or vitamin D. During this period 558 women were referred, of whom 211 were excluded for the reasons described above. The remaining pool of 347 women were used to match with the controls (two controls:one case) by age (within 5 yr) and body mass index (within 2 units).

Women with RA were interviewed and examined in a dedicated research clinic and their case notes were reviewed. We obtained general information and a detailed RA history including duration of disease, rheumatoid factor, erosive status, modified Health Assessment Questionnaire (HAQ) score [9] and previous and current drug treatment, including steroid therapy. The women were asked to keep a record of the number of hours per day that they spent on their feet (standing and walking) for the 7 days prior to the clinic visit. Disease activity was assessed by an experienced metrologist (DJ). Early morning stiffness, 28 joint count (swollen and tender joints), ESR and HAQ scores were determined. Assessment of lower limb joint disease was also carried out. For the purposes of this study, symptomatic hip disease was defined as pain, stiffness or aching in or around the hip on most days of the month over the last 12 months and/or pain on range of movement of the hip joints when examined. Similarly symptomatic knee disease was defined as pain, stiffness or aching in or around the knee on most days of the month over the last 12 months and/or pain on range of movement of the knee joints or swelling of the knee joints when examined. Symptomatic ankle/feet disease was defined as pain, stiffness or aching in or around the ankles/feet on most days of the month over the last 12 months and/or pain on range of movement or tenderness on palpation of the ankles/feet when examined.

Cases and controls underwent bone density measurement and a falls risk assessment. Dual-energy X-ray absorptiometry using a Lunar DPX device (Lunar, Madison, WI, USA) was used to measure anteroposterior bone mineral density (BMD) of the L2–L4 lumbar spine (LS) and femoral neck (FN). These measurements were carried out in the Osteoporosis Unit, St George's Hospital over an 8-month period. Daily calibration measurements using an external phantom were performed and monitored for machine drift. No significant drift was noted during the study period. Precision was calculated by the method of Gluer et al. [10] and at our centre is 1.3% for the lumbar spine and 1.8% for the femoral neck.

Falls risk assessment was performed as previously described [11]. These tests of falls have previously been shown to be predictors of hip fracture in two large cohort studies of older women: the Study of Osteoporotic Fractures (SOF) [5] and the Epidémiologie de l’Ostéoporose prospective study (EPIDOS) [6]. The tests are: (i) binocular corrected visual acuity (VA); (ii) ability to carry out heel–toe walking, a test of dynamic balance; and (iii) ability to do five standups without arm use, a test of lower limb muscle and joint function. VA (corrected) was measured using a Snellen chart at 6 feet. Heel–toe walking over four steps was assessed as described in the EPIDOS study and graded accordingly. Grade 1 is four consecutive heel–toe steps, grade 2 is unable to do four consecutive steps without stepping off the line or touching the examiner, grade 3 is unable or unwilling to put the feet in the heel–toe position, and grade 4 is unable to do the test or use of a walking stick or other ambulatory aid. Ability to perform five standups without arm use was graded as Yes or No. For the purposes of this study we considered women to have a significant increase in fall risk if VA was very low (0.5 or less) or if they were unable to perform standups or if they had substantial difficulty with heel–toe walking (EPIDOS grade 3 or 4). We chose to analyse the heel–toe walking by comparing grades 1 and 2 vs 3 and 4 as there is a clear difference between performance that is most obvious between grades 2 and 3.

Statistical analysis
We estimated that by comparing 100 RA patients with 200 controls we would have 90% power at 5% significance to detect differences in risk of hip fracture due to fall risk between the two groups of 12–17% (depending on the fall risk factor). Risk differences are given with 95% confidence intervals and comparisons made using the {chi}2 test. The effect of current steroid treatment on risk factors is presented as an odds ratio and logistic regression used to adjust for HAQ score. Continuous data are presented as mean (S.D.) unless stated otherwise and comparisons between groups were made using Student's t test for normally distributed variables and the Mann–Whitney U test for skewed data. SPSS for Windows version 10 was used for these analyses.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
We identified a total of 143 women aged 65 and over with RA who were being treated at St Helier Hospital at the start of the study, of whom 103 consented to participate. The characteristics of the participants and the non-participants are shown in Table 1. Age, duration of RA and most recent ESR at the time of the study were identified from case notes for the 40 non-participants and were compared with those of participants. No significant differences in these parameters were found between the participants and non-participants. Of the participants, 82/103 (80%) had erosive disease, 87/103 (85%) were being treated with a disease-modifying drug and 39/103 (38%) were being treated with steroids. Hip joint replacement had been performed on 18/103 (17%) of women, knee replacement in 13/103 (13%) and ankle/foot surgery in 19/103 (20%).


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TABLE 1. Characteristics of participants and non-participants

 
Bone densitometry could not be performed on a total of 6 RA patients (four did not wish to have this performed and two had bilateral hip replacements), leaving 97 patients who had both fall risk and FN BMD measured.

Fall risk in women with RA (n = 103) compared with controls (n = 206)
The cases and controls were matched as described and the comparative data are shown in Table 2. Heel–toe walking was abnormal (grade 3 and 4) in 45% of rheumatoid women compared with only 14% of controls (difference 32%, 95% CI 25 to 44; P<0.001). Similarly, inability to perform standups was found in 32% of the rheumatoid women compared with only 13% of the controls (difference 19%, 95% CI 9 to 29; P<0.001). The prevalence of low visual acuity was exactly equal in the two groups, at 43%. More women with RA gave a history of a previous fall since the diagnosis of RA compared with controls (54 vs 44%), but this just failed to reach statistical significance (difference 10%, 95% CI –2 to 22).


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TABLE 2. Characteristics of cases and controls

 
Osteoporosis in women with RA (n = 97)
FN bone density was classified according to WHO criteria as being osteoporotic in 31/97 (32%), osteopenic in 50/97 (52%) and normal in 16/97 (16%). Respective values for the LS were 28/97 (29%), 36/97 (37%) and 33/97 (34%). The ESR was significantly higher in women with FN osteoporosis than those without, with a mean of 38 (25) and 29 (19) mm/h respectively (P = 0.043). However, duration of RA, HAQ score, swollen and tender joints and hours on feet were not related to FN osteoporosis.

Fall risk in women with RA (n = 97)
Based on the definitions described in Patients and methods, increased fall risk was found in 66/97 (89%) of the RA patients. The proportion of women who had increased risk of hip fracture due to increased fall risk alone (that is, they did not have FN osteoporosis) was 48/97 (49%). Of the 31 women with FN osteoporosis, 23 (74%) also had an increased risk of falling (at least one of the fall risk factors was present).

Determinants of fall risk factors (n = 97)
Patients with low VA were significantly older compared with those with normal VA [75 (13) vs 69 yr (11), P = 0.04] but there were no other differences.

Data for heel–toe and standup tests were combined (as the findings were similar for each test individually) and are presented in Table 3. Those patients at highest fall risk (underperformance in both tests; n = 27) are compared with those with the lowest risk (performed normally in both tests; n = 48). The remaining 22 patients are those with intermediate risk (underperformance in either heel–toe walking or standups). Those women who had highest fall risk in these tests had significantly higher HAQ scores, higher tender joint counts and spent less time on their feet. We also found that there was an inverse relationship between the number of hours on feet and the HAQ score (Spearman's r = –0.31; P = 0.02).


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TABLE 3. Patient characteristics according to heel–toe walking ability and ability to perform standups

 
Current steroid treatment (n = 39, mean dose of prednisolone 5 mg/day) was associated with increased prevalence of fall risk factors [odds ratio 2.35 (1.03 to 5.39)] but this was not independent of HAQ scores.

Lower limb joint involvement and fall risk factors (n = 97)
The patients’ fall risk was also examined according to lower limb joint symptoms. Current lower limb joint symptoms or signs (see Patients and methods for definition used) were present for the hip in 28% of women, knee in 56% and ankle/foot in 62%. Women with knee symptoms/signs were more likely to have abnormal heel–toe walking compared with those with without knee symptoms (66 vs 42%; P<0.001). Similarly, inability to perform standups was also significantly impaired (77 vs 42%, P<0.001). For women with ankles/feet symptoms, abnormal heel–toe was also more likely (73 vs 48%; P = 0.025), as was inability to perform standups (81 vs 52%; P = 0.025). Hip joint symptoms did not have any effect on the performance of these fall risk factors.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
In this study we examined whether fall risk is increased in women with RA, and demonstrated that risk factors for falls were three times more prevalent in rheumatoid patients compared with the controls. We also showed that a substantial proportion of women (74%) with FN osteoporosis also had increased risk of hip fracture due to falling.

The most significant associations with fall risk were the level of disability as defined by the HAQ score and the tender joint count, whilst variables such as disease duration, ESR and steroid treatment were not associated (Table 3). Tender joint counts were higher in women at higher risk of falling but this relationship was not found for swollen joints. As tenderness depends on patient perception, whereas swelling is a more objective sign, this raises the question as to whether pain perception may affect dynamic balance or muscle strength, particularly as dissociation between patient perception of pain and objective signs of joint inflammation has been reported previously [12]. The distribution of lower limb joint symptoms also seemed to be important in defining patients at high risk of falling. Thus, those women with knee and ankle/foot symptoms were at greatest risk whereas hip involvement did not seem to have an effect. However, this observation needs to be interpreted with caution as it may be that the tests used (heel–toe walking and standups) are not sensitive to the effect of hip joint disease. Indeed, a previous population-based case–control study of non-rheumatoid individuals with new onset of hip pain showed that falls were more common in the previous 12 months in women (although no relationship was seen for men) [13].

This study highlights that the risk of falling is common in older women with RA. Thus, increased fall risk (based on the definitions used in this study) was found in 89% of the women studied. Although the evidence base for interventions to reduce falling in older women is increasing, whether these interventions could be applied to women with RA is at present unclear. In theory, potential interventions in women with RA to reduce falling include control of disease activity, rehabilitation or exercise therapy, balance training, occupational therapy, home assessment and treatment of vitamin D deficiency. We are not aware of any studies showing that fall risk can be improved by reducing RA disease activity. A recent study suggested that ‘brief rehabilitation’ can improve quadriceps sensorimotor function and reduce HAQ scores [14]; however, ‘intensive dynamic exercise therapy’ did not improve HAQ scores [15, 16] and therefore may not reduce risk of falling. Vitamin D deficiency is common in RA [17–20] and low levels of vitamin D in non-rheumatoid individuals are associated with reduced functional performance, weaker quadriceps and instability [21], and falling [22]. Furthermore, recent evidence in non-rheumatoid individuals suggests that treatment with calcium and vitamin D reduces body sway [23] and falls [24], although vitamin D supplementation alone has insufficient evidence for improvements in physical function [25], particularly if dietary calcium intake is low [26]. Other interventions, such as hip protectors to reduce hip fracture, are unlikely to be helpful because in our personal experience women with RA do not seem to be able to put them on [27]. We also found that the HAQ score was associated with increased fall risk, and therefore this could provide an easy screening tool for falling in women with RA, although more work needs to be done on a threshold for clinical use.

The strengths of this study include our ability to demonstrate that participants and non-participants were similar. Also, the fall risk factors we used were predictive of an important consequence of falling (namely hip fracture) rather than risk factors previously shown just to predict falling. Thus, hip fracture risk increases from a relative risk of 1 for normal VA (VA > 0.7 in decimal units) to 1.9 (VA 0.5–0.7) to 3.0 (VA 0.3–0.4) and 4.3 (VA ≤0.2). 6Similarly, for heel–toe walking hip fracture risk increases from a relative risk of 1 (grade 1) to 1.7 (grade 2), 3.0 (grade 3) and 5.2 (grade 4) [6]. Inability to perform five standups is associated with a relative risk of hip fracture of 2.2 compared with ability to perform standups [5]. Limitations of this study are the cross-sectional study design and the use of fall risk factors as surrogates of falling rather than a prospective study of falling in women with RA. The latter, however, would be a major undertaking. Our data do not allow us to separate out whether RA is independent of physical activity as a risk factor for falling. We are simply describing the characteristics of patients who have abnormal or poor performance in the fall risk factor tests and therefore are at increased risk of falling and fracture. We were unable to blind the observers to the patients’ diagnosis of RA; therefore, this could potentially bias the tests of fall risk, particularly heel–toe walking. However, as we used a cut-off for normal vs abnormal of grade 2 (able to walk heel–toe but falls off line) vs grade 3 (unable to put feet into heel–toe position) and provided a training session to help ensure classification was consistent, we think that this bias will have been minimized. Our patients were Caucasian women, so we cannot comment on women of other races or men. Their RA was well controlled, so the effect of more active disease is unclear, particularly as we found no correlation between markers of disease activity and falling. The use of women referred for bone densitometry as controls to compare fall risk could have introduced bias. However, this bias would have been to make our observation of the threefold increase in prevalence of fall risk factors in women with RA an underestimate of the risk (on the assumption that a referred population may have a higher risk of falling and osteoporosis compared with a ‘normal’ population).

In summary, we have demonstrated that fall risk factors predictive of hip fracture are common in women with RA. Fall risk needs to be considered when RA patients are being treated for osteoporosis and further work needs to be done to help reduce the risk of falling and fracture in women with RA.


    Acknowledgments
 
This work was supported by the Arthritis Research Campaign (Grant PO578) and by the R&D Fund of Epsom and St Helier NHS Trust.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 27 February 2004; revised version accepted 15 June 2004.



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