SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Objective

African Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment.

Methods

Risk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10-year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing.

Results

Participants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3–86%, depending on age and body mass index (BMI). Ten-year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55–69 years of age with low/normal BMI, and in those ≥70 years of age with BMI ≥30 kg/m2.

Conclusion

A high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low-risk patients accurately. Systematic application of FRAX to screen high-risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Osteoporosis is recognized as a major source of morbidity in rheumatoid arthritis (RA), with up to one-third of women with RA experiencing a fracture within 5 years of followup (1). Compared with others, patients with RA are twice as likely to experience hip fracture (2) and >4 times as likely to have vertebral deformities suggestive of fracture (3). The impact of hip fractures can be substantial, with approximately one-half of patients being unable to walk without assistance and up to one-fourth requiring long-term nursing care (4). Likewise, vertebral compression fractures lead to significant declines in quality of life (5), resulting in both chronic pain and disability (6), and are associated with a >4-fold increase in mortality (7).

Prior investigations of osteoporosis and bone mineral density (BMD) in RA have almost exclusively involved populations of European ancestry. The lack of such studies in African Americans represents an important knowledge gap given existing racial/ethnic disparities in osteoporosis treatment and fracture-related outcomes observed in this population (8–12). We have previously shown that African Americans at increased risk for fracture are far less likely than whites to receive appropriate diagnostic tests in addition to preventive therapies, including prescription osteoporosis medications (11).

Previously, the decision of whether to treat patients with RA for osteoporosis has been based primarily on BMD T scores measured using dual x-ray absorptiometry (DXA) (13). Recent efforts have emphasized the role of absolute fracture risk assessment, particularly with the release of the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) (14). FRAX is an Internet-based tool that provides 10-year estimates of absolute risk of fracture for individual patients. FRAX estimates 10-year absolute risk for both hip fracture and major osteoporotic fracture, incorporating 9 clinical risk factors, and it can be calculated with or without femoral neck BMD (14).

Recently released guidelines from the National Osteoporosis Foundation (NOF) incorporate FRAX (15), and osteoporosis treatment is recommended if any 1 of the following criteria are met: 1) history of previous hip or vertebral fracture, 2) a T score of −2.5 or less for the femoral neck, total hip, or spine, 3) low BMD and FRAX 10-year absolute risk of hip fracture ≥3%, and 4) low BMD and FRAX 10-year absolute risk of major osteoporotic fracture ≥20%. If patients do not have one of the clinical indications for osteoporosis treatment (e.g., prior fracture), FRAX without BMD could potentially identify lower- versus higher-risk patients on the basis of integrating clinical risk factor information. Some patients might then be targeted for further evaluation, including BMD testing. This 2-step screening approach could potentially lead to a more efficient use of BMD testing resources.

The purpose of this analysis was to evaluate relationships between RA disease features and BMD, and to describe the proportion of African American patients with early RA who would be recommended for treatment under the new NOF guidelines. To facilitate the latter evaluation, we used FRAX to estimate the absolute 10-year fracture risk. Furthermore, we sought to focus on patients who might be treated on the basis of exceeding the NOF fracture risk thresholds (10-year risk of hip fracture ≥3% or major fracture risk ≥20%) to determine whether including BMD in the FRAX calculations impacted treatment decisions and, if so, which patient factors influenced these differences.

SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Study subjects and clinical measures.

Study subjects (n = 324) were participants in the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry (16, 17), enrolled between October 2000 and July 2006. The CLEAR Registry contains clinical data, DNA, and other biologic samples that are available to approved users (details are available at http://www.dom.uab.edu/rheum/CLEAR%20home.htm).

Participants were of self-reported African American race/ethnicity, satisfied the American College of Rheumatology (formerly, the American Rheumatism Association) classification criteria for RA (18), and had a disease duration of <2 years (17). Baseline data were collected at enrollment and included medical history (e.g., medications, use of calcium/vitamin D supplementation), smoking history, alcohol use, and menopausal status for women. Measures of disease activity/severity included the Health Assessment Questionnaire (HAQ) disability index (19), pain (0–10 scale), rheumatoid nodules, tender joints (range 0–42), swollen joints (range 0–40), and the presence of radiographic erosions (a modified Sharp/van der Heijde erosion score ≥1) (20). At the time of this analysis, baseline radiographic scores were available for 183 of 324 patients.

BMD measurement.

Femoral neck and lumbar spine (L1–L4, anteroposterior) BMD was measured at enrollment using DXA (21). BMD was not measured on a small subset of patients due to the presence of either bilateral total hip replacements or other artifact interfering with either hip (n = 9) or vertebral measurements (n = 4). Because the DXA machine type varied by site, BMD values were standardized to Hologic BMD (Hologic, Bedford, MA) using published conversion equations (22).

Site-specific T scores were calculated by subtracting peak referent BMD for white women from the patient's value and dividing the difference by the referent SD. Z scores were calculated using sex-specific African American referent data specific to the participant's age decile (peak referent BMD ages 20–29 years, 30–39 years, etc.). For the spine, we used the manufacturer's reference database (Hologic), and for the hip, we used reference data from the Third National Health and Nutrition Examination Survey (23). Reduced BMD adjusted for age decile was defined as a Z score −1.0 or less. Osteopenia and osteoporosis were defined using the T score thresholds established by the WHO for diagnosis in postmenopausal white women (24). Osteoporosis is defined as a BMD T score ≥2.5 SDs below the young adult mean in women. Osteopenia is defined as a BMD T score between 1–2.5 SDs below this mean.

Laboratory measures.

Laboratory measures were obtained from serum and plasma samples obtained at enrollment. IgM rheumatoid factor (IgM-RF) in IU/ml (Inova Diagnostics, San Diego, CA), antibodies against cyclic citrullinated peptide (anti-CCP) in units/ml (Diastat; Axis-Shield Diagnostics, Dundee, UK), N-telopeptide (NTX) in nmoles of bone collagen equivalents (BCE; Wampole Laboratories, Cranbury, NJ), and bone alkaline phosphatase (BAP) in units/liter (Quidel, San Diego, CA) were measured using enzyme-linked immunosorbent assay. Positive values for RF (≥9.5 IU/ml) and anti-CCP antibody (≥5 units/ml) were defined as previously reported (25). Elevations in NTX (premenopausal women >19.0 nM BCE, postmenopausal women >33.9 nM BCE, men >24.2 nM BCE) and BAP (premenopausal women >30.6 units/liter, postmenopausal women >43.4 units/liter, men >41.3 units/liter) were defined using cutoffs provided by the manufacturers. High-sensitivity C-reactive protein (hsCRP) levels in mg/liter were measured with an immunoturbidimetric assay on a Hitachi 917 autoanalyzer (Roche Diagnostics, Indianapolis, IN), with the use of reagents and calibrators from Denka Seiken (Tokyo, Japan; normal value <3 mg/liter). Plasma estradiol in pg/ml (Research Diagnostics, Flanders, NJ) and 25-hydroxyvitamin D [25(OH)D] in nmoles/liter (IDS, Boldon, UK; insufficiency at ≤37.5 nmoles/liter) (26) were measured using commercially available radioimmunoassay.

FRAX.

Ten-year risk of hip fracture and major osteoporotic fracture were calculated using the WHO FRAX tool (available online at http://shef.ac.uk/FRAX) specific to African Americans (calculations completed October 25, 2008). FRAX incorporates the following clinical risk factors: age, sex, weight, height, previous fracture, parental history of hip fracture, current smoking status, glucocorticoid use, RA, other causes of secondary osteoporosis, alcohol use, and, if available, femoral neck BMD (T scores from men and women referent to white women). Excluding the 9 persons for whom femoral neck BMD was not available, all variables that are required for FRAX were measured in this population, except that parental history of hip fracture was not measured in this cohort and therefore was entered as “no” for all participants, and only information about clinical (but not radiographic) vertebral fractures was available. Additionally, the CLEAR Registry and FRAX did not ascertain alcohol use in the same way, and this variable was considered to be present if the subject reported regular alcohol use. Parenthetically, the presence of other secondary causes of osteoporosis does not affect fracture risk estimates produced by the FRAX calculator if patients have RA. Ten-year absolute risk estimates for hip fracture and major osteoporotic fracture (hip, clinical vertebral, forearm/wrist, and humerus) were calculated for each individual with and without BMD.

Updated 2008 NOF treatment recommendations.

We applied the 2008 NOF guidelines, as outlined in the Introduction, to estimate the proportion of individuals who would be recommended for treatment by age and body mass index (BMI). Although we used T scores referent to white women in FRAX calculations as recommended by the WHO, T scores used in the remainder of the NOF recommendations were referent to sex-matched whites (27).

We used FRAX with BMD to identify which patients met or exceeded a 10-year risk for hip fracture ≥3%, or for major fracture ≥20%. We then used FRAX to recompute fracture risk after removing BMD information. The proportion of persons meeting the fracture risk threshold using FRAX with BMD compared with FRAX without BMD were considered, stratified by age (40–54, 55–69, and ≥70 years) and BMI (<25, 25 to <30, and ≥30 kg/m2). The goal of this analysis was to determine whether it might be possible to identify groups of patients based upon age and BMI that were at such low (or high) risk for fracture based only on FRAX without BMD that obtaining BMD was unnecessary because it did not change whether or not they exceeded the NOF-specified fracture risk thresholds. Patients who exceeded the risk thresholds when using FRAX without BMD but who did not exceed it when using FRAX with BMD (or vice versa) were considered discordant. The number needed to screen with DXA was computed for various age and BMI strata. The number needed to screen is the number of persons that need to undergo DXA in order to find 1 discordant person. For this exploratory subanalysis, and because we wished to focus on FRAX-computed fracture risk exclusively, other clinical criteria (e.g., prior hip fracture) that might have made a patient recommended for treatment under the 2008 NOF guidelines were not considered.

Statistical analyses.

Patient characteristics were summarized using mean ± SDs and frequencies. Associations of patient characteristics with femoral neck and lumbar spine BMD were examined for each site using backward stepwise multivariate linear regression (P ≤ 0.25 required to enter model, P ≤ 0.05 to remain). Sex and menopausal status were incorporated as a single variable so that premenopausal and postmenopausal women were compared with men as the referent group. Additional variables examined as determinants of BMD included age (years), BMI (<25, 25 to <30, and ≥30 kg/m2), ever smoking, alcohol use, estradiol concentration, 25(OH)D concentration and deficiency, hsCRP concentration and elevation (≥3 mg/liter), HAQ score, disease duration, tender/swollen joint counts, pain score, presence of radiographic erosions, nodules, glucocorticoid use, and autoantibody status. All analyses were performed using SAS, version 9.1 (SAS Institute, Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Sociodemographic, health, and disease-specific characteristics of study participants are shown in Table 1. The cohort was predominantly female (81%) with an overall mean age of 51 years (median 51 years, range 21–86 years) and a mean disease duration of just over 1 year. Approximately one-half of the participants had a previous smoking history, and approximately one-half met the criteria for obesity (BMI ≥30 kg/m2). Approximately 80% had previously taken systemic glucocorticoids for their RA, and approximately one-half were deficient in 25(OH)D (≤37.5 nmoles/liter). The proportion of patients meeting the T score criteria for osteoporosis (T score −2.5 or less at either the lumbar spine or femoral neck) was 4%. Reduced BMD (Z score −1 or less) was observed in approximately one-third (31%) of patients. Elevations in circulating NTX and BAP were observed in 9.2% and 9.6% of patients, respectively. Measures of RA disease activity suggested moderate to severe disease with a mean HAQ score of 1.6 and mean tender and swollen joint counts of 6 and 12, respectively. A total of 70% of participants were seropositive for IgM-RF, and 61% were seropositive for anti-CCP antibody.

Table 1. Characteristics of African American subjects with recent-onset RA (n = 324)*
CharacteristicValue
  • *

    Values are the percentage unless otherwise indicated. RA = rheumatoid arthritis; BMI = body mass index; 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; NTX = N-telopeptide; BCE = bone collagen equivalents; BAP = bone alkaline phosphatase; anti-CCP = anti–cyclic citrullinated peptide; IgM-RF = IgM rheumatoid factor; hsCRP = high-sensitivity C-reactive protein; HAQ = Health Assessment Questionnaire.

  • Determined using referent normative data from white women. BMD values standardized to Hologic machine (22).

  • Sex adjusted using African American referent database.

  • §

    Elevated serum levels of NTX: premenopausal women >19.0 nM BCE, postmenopausal women >33.9 nM BCE, men > 24.2 nM BCE.

  • Elevated serum levels of BAP: premenopausal women >30.6 U/liter, postmenopausal women >43.4 units/liter, men >41.3 units/liter.

Sociodemographics and anthropormetrics 
 Age, mean ± SD years51 ± 13
 Sex 
  Men19
  Postmenopausal women31
  Premenopausal women50
 BMI, kg/m2 
  <2522
  25 to <3027
  ≥3051
Fracture-related risk factors and other bone health determinants 
 Prior fracture 
  Hip1.3
  Clinical vertebral1.6
  Other fracture21
 Ever glucocorticoid use79
 Glucocorticoid daily dose, mean ± SD mg prednisone7.3 ± 7.2
 25(OH)D deficient (≤37.5 nM/liter)49
 25(OH)D, mean ± SD nM/liter41 ± 16
 Estradiol, mean ± SD pg/ml36 ± 35
 Vitamin D supplementation15
 Ever antiresorptive therapy19
 Calcium supplementation42
 Current alcohol use17
 Ever smoking52
BMD and bone turnover markers 
 Femoral neck or lumbar spine T score −1.0 or less29
 Femoral neck or lumbar spine T score −2.5 or less4
 Femoral neck or lumbar spine Z score −1.0 or less31
 NTX, mean ± SD nM BCE§17 ± 6
 Elevated NTX9.2
 BAP, mean ± SD units/liter26 ± 11
 Elevated BAP9.6
RA disease characteristics 
 Disease duration, mean ± SD months13 ± 7
 Subcutaneous nodules14
 Anti-CCP antibody positive61
 IgM-RF positive70
 Swollen joint count, mean ± SD (0–40)6 ± 7
 Tender joint count, mean ± SD (0–42)12 ± 11
 Pain, mean ± SD (0–10)6 ± 3
 hsCRP level, mean ± SD (mg/liter)16 ± 42
 hsCRP level, ≥3 mg/liter62
 HAQ disability index score, mean ± SD (0–3)1.6 ± 0.9

Results from the multivariate analysis examining the association of patient factors with BMD are shown in Table 2. There were no associations of RA activity, severity, or erosions with BMD at either site on a univariate or multivariate level. Likewise, there were no associations of glucocorticoid use (ever use, daily, or cumulative dose), 25(OH)D (concentration or deficiency), or hsCRP (concentration or elevation) with BMD. BMI was independently and positively associated with higher BMD values at both sites. In addition, increases in plasma estradiol concentration were associated with higher spine BMD, whereas younger age and male sex were associated with increased femoral neck BMD.

Table 2. Univariate and multivariate associations of patient factors with BMD (gm/cm2) measurements of lumbar spine (L1–L4) and femoral neck among African Americans with recent-onset RA*
 Lumbar spine (L1–L4)Femoral neck
Univariate B coefficient (P)Multivariate B coefficient (P)Univariate B coefficient (P)Multivariate B coefficient (P)
  • *

    All factors entered into multivariable model with P ≤ 0.25 at univariate level with stepwise removal until all remaining P ≤ 0.05. Additional variables examined (all P > 0.25 at univariate level) included 25(OH)D concentration, hsCRP elevation, and usual daily and cumulative glucocorticoid dose (prednisone equivalent). See Table 1 for definitions.

  • Based on the modified Sharp/van der Heijde erosion score ≥1 (n = 183).

Age, years−0.003 (0.0006)−0.005 (< 0.0001)−0.005 (< 0.0001)
Sex/menopausal status    
 MenReferentReferentReferentReferent
 Premenopausal women0.031 (0.27)0.031 (0.18)−0.063 (0.006)
 Postmenopausal women−0.016 (0.53)−0.058 (0.009)−0.057 (0.006)
BMI, kg/m2    
 <25ReferentReferentReferentReferent
 25 to <300.080 (0.003)0.078 (0.007)0.067 (0.004)0.073 (0.0004)
 ≥300.137 (< 0.0001)0.127 (< 0.0001)0.128 (< 0.0001)0.134 (< 0.0001)
Ever smoking−0.016 (0.43)−0.026 (0.12)
Current alcohol use0.013 (0.62)0.013 (0.57)
Estradiol, pg/ml0.001 (0.001)0.0007 (0.02)0.001 (< 0.0001)
25(OH)D deficiency0.022 (0.30)0.013 (0.50)
hsCRP level, mg/liter0.0002 (0.49)0.0001 (0.55)
HAQ score (0–3)0.009 (0.39)0.007 (0.47)
Tender joint count0.0006 (0.51)0.0007 (0.32)
Swollen joint count0.001 (0.37)0.0005 (0.63)
RA disease duration−0.0006 (0.65)−0.0004 (0.72)
Ever glucocorticoid use0.004 (0.88)−0.0008 (0.97)
Calcium supplementation0.001 (0.95)−0.018 (0.28)
Pain (0–10)0.007 (0.03)0.008 (0.02)0.008 (0.008)
Radiographic erosions0.018 (0.53)0.012 (0.61)
Nodules−0.019 (0.50)−0.023 (0.34)
Anti-CCP positive−0.006 (0.79)0.033 (0.08)
IgM-RF positive0.010 (0.66)0.045 (0.03)
R2 0.14 0.33

The proportion of patients with RA classified as recommended for treatment based on 2008 NOF guidelines (as described in the Introduction) is shown in Table 3. The proportion varied dramatically by age and BMI, ranging from a low of 3% (age 40–54 years, BMI ≥30 kg/m2) up to 86% (age ≥70 years, BMI 25 to <30 kg/m2). Focusing exclusively on the 10-year hip fracture risk ≥3% or major fracture risk ≥20% calculated without BMD (and not any other NOF criteria), the proportion meeting either of these risk thresholds is shown in Figure 1A. This analysis was repeated using FRAX with BMD and is shown in Figure 1B. As shown, the proportion of people exceeding the 3%/20% fracture risk thresholds was generally higher using FRAX without BMD, and varied substantially by age and BMI. Only 10% (n = 29) of people were discordant in crossing the hip fracture ≥3% or the major fracture ≥20% thresholds when comparing results from FRAX with and without BMD (Figure 1). Among subjects with discordance, a majority had normal femoral neck T scores (T score greater than −1.0), the remainder had femoral neck T scores less than −1.0 but greater than −2.0, and none had osteoporosis. The number needed to screen for DXA leading to identification of 1 discordant person varied by age and BMI. Among persons ≥70 years, 2–3 individuals would need to be tested with DXA to identify 1 discordant person. For persons age 55–69 years, at least 4–6 individuals would need to be tested with DXA to identify 1 discordant person.

Table 3. Proportion of African Americans with recent-onset RA who would be recommended for treatment under the 2008 National Osteoporosis Foundation guidelines, by age and BMI*
BMI, kg/m2Age, years
40–5455–69≥70
  • *

    Values are the percentage (95% confidence interval). See Table 1 for definitions.

<255 (1–18)36 (17–59)71 (29–96)
25 to <307 (1–17)11 (1–35)86 (42–100)
≥303 (1–8)8 (2–20)17 (2–48)
thumbnail image

Figure 1. The proportion of African American patients with recent-onset rheumatoid arthritis with hip fracture risk ≥3% or major osteoporotic fracture risk ≥20%. Estimates generated using the World Health Organization Fracture Risk Assessment Tool (FRAX) (A) without and (B) with bone mineral density (BMD) data. BMI = body mass index.

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Although the incidence of osteoporosis is lower in African Americans than whites (28), African Americans experiencing fracture have substantially worse outcomes. Compared with whites, African Americans suffering from hip fracture have substantially longer hospitalizations, are more likely to be nonambulatory at the time of discharge (8), and have higher mortality (9). Additionally, African Americans are less likely than whites to receive the same degree of physical rehabilitation (29) or medical intervention following fracture (12), which are treatments that have been shown to be effective in African Americans (30). In this population of African Americans with early RA, a majority of patients (∼80%) ≥70 years of age with normal or low BMI were recommended for treatment under the recently-revised NOF guidelines. For patients between 55 and 69 years of age, 8–36% of people were recommended for treatment, varying based upon BMI. We also found that using FRAX without BMD was an efficient approach to identifying people at low enough fracture risk based on clinical risk factors such that measuring BMD was not necessary.

The clinical variables included in FRAX can be collected in minutes with a simple questionnaire and may be available within many electronic health records to identify higher-risk patients in a more systematic fashion. A strategy of case finding through the use of FRAX without BMD may be effective in targeting patients for additional evaluation (including DXA). This strategy might be most feasible within large, integrated health systems (i.e., Veterans Affairs, Kaiser Permanente), and it has the potential of reducing the racial/ethnic disparities that too often characterize osteoporosis management in African Americans (11, 12).

It is likely that in the near future, FRAX results will be incorporated as a component of DXA reports, assuming that the necessary data is collected by technicians performing these measurements. In the absence of the routine inclusion of FRAX results in DXA reports, there are currently several important operational issues to consider in using FRAX as part of day-to-day patient care. These logistic issues include the need for Internet access, the proprietary nature of FRAX and the associated lack of transparency regarding the impact of the data elements used to estimate long-term risk, and patient preferences regarding the risk threshold that must be exceeded in order to accept prescription osteoporosis treatment.

Although BMD measurement with DXA has long served as the gold standard for fracture risk assessment, its inclusion in FRAX appears to have widely variable incremental yield among African American subjects with recent-onset RA. In our study population, the addition of BMD data to the fracture risk estimate led to changes in risk assessment in as few as 10% of patients. DXA provided the greatest amount of incremental value in assessing fracture risk in patients 55–69 years of age with a BMI <30 kg/m2, and among those ≥70 years of age with a BMI ≥30 kg/m2. In most cases of discordance, patients went from being above the fracture risk threshold of 3%/20% (computed under FRAX without BMD) to below the threshold under FRAX with BMD. Based on our results, a change in the FRAX risk assessment would occur for ∼1 of every 3 patients ≥70 years of age screened with DXA.

These results have important implications. In the absence of other clinical indications to treat osteoporosis (e.g., prior hip fracture), our results show that a “do not treat” result based upon fracture risk could obviate the need for BMD measurement because its inclusion in the FRAX calculation is highly unlikely to change the risk assessment and corresponding treatment decision. On the other hand, DXA measurement in high-risk patients may lead to a change in treatment decision to not treat, and thus minimize exposure to potentially unnecessary treatments.

Although glucocorticoid use and measures of RA disease severity (e.g., RF positivity, radiographic erosions) have been potentially associated with RA-associated bone loss, these factors do not appear to significantly influence BMD in African Americans early in the course of RA. Thus, RA-related factors in this population should not be used to guide BMD referral and do not appear to portend added risk beyond the RA diagnosis itself, at least early in the course of the disease.

There are limitations to this study. This study involved African American patients with RA recruited from select centers in the Southeast US, limiting the generalizability of these findings. These results cannot be extended to other disease states or other racial/ethnic populations, underscoring the need for additional study. Because this investigation involved patients with limited disease duration (and limited glucocorticoid exposure), it is possible that these results may not apply to African Americans with more longstanding RA. It may be reasonable, for instance, to obtain baseline BMD measurement in an otherwise low-risk RA patient to guide the future management of glucocorticoid-induced osteoporosis. We also recognize that the cohort was relatively young (mean age 51 years), and that most treatment guidelines focus on postmenopausal women and older men. However, we included these younger populations because RA is a well-established, independent risk factor for osteoporosis and fracture (31), and glucocorticoid-induced osteoporosis management guidelines (32, 33) pertain to younger patients (just as FRAX calculates fracture risk for individuals as young as 40 years of age). The high prevalence of overweight (76%) and obese (51%) participants in this population impacted our results, decreasing the proportion of subjects recommended for osteoporosis treatment. However, it is important to recognize that prevalence rates of overweight/obese subjects in this study are similar to those from a recent national, population-based investigation of African Americans (34). Also, select risk factors (e.g., alcohol use) in this cohort were defined differently than in the WHO FRAX, and only lumbar spine and femoral neck BMD (but not total hip BMD) were available to identify osteoporosis based upon a T score −2.5 or less.

There are limitations to the FRAX and NOF guidelines worth noting. FRAX does not incorporate every clinical variable that may be important in fracture risk assessment (e.g., fall risk) and lacks information on dose-response relationships (e.g., glucocorticoid dose). Additionally, it is important to recognize that epidemiologic studies of fracture risk in African Americans are scarce, and the accuracy of FRAX for fracture prediction in African Americans has not been validated. FRAX represents an important starting point in the complex task of risk assessment and fracture prevention, but should not be regarded as a substitute for clinical judgment. Finally, only weak evidence exists that the benefit of bisphosphonates and other osteoporosis medications extends to persons with T scores greater than −2.5 (i.e., osteopenia).

Despite its limitations, this study has notable strengths. This effort represents the single largest study to date of BMD and fracture risk assessment in African Americans with RA. With the exception of parental fracture history, all of the necessary data were available to allow for the calculation of 10-year fracture risk in this group. These data, coupled with standardized DXA data and detailed information on RA-specific disease characteristics, provided the unique opportunity to examine BMD status and promote improved fracture risk assessment and osteoporosis management in this unique and understudied population. We conclude that systematic application of FRAX to screen high-risk groups, including African Americans with RA, may be useful in targeting patients for BMD measurement, and in the process may reduce unnecessary testing and treatment in fracture prevention.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Mikuls had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Curtis, Moreland, Bridges, Mikuls.

Acquisition of data. Callahan, Moreland, Bridges, Mikuls.

Analysis and interpretation of data. Curtis, Arora, Donaldson, Alarcón, Moreland, Mikuls.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The CLEAR investigators are S. Louis Bridges, Jr., MD, PhD, Director, George Howard, DrPH, Co-Director, Graciela S. Alarcón, MD, MPH: University of Alabama at Birmingham; Doyt L. Conn, MD: Emory University; Beth L. Jonas, MD, Leigh F. Callahan, PhD: University of North Carolina; Edwin A. Smith, MD: Medical University of South Carolina; Richard D. Brasington, Jr., MD: Washington University; Ted R. Mikuls, MD, MSPH: University of Nebraska; and Larry W. Moreland, MD, Co-Director: University of Pittsburgh.

We gratefully acknowledge CLEAR Registry staff and coordinators at the following sites: Stephanie Ledbetter, MS, Zenoria Causey, MS, Selena Luckett, RN, CRNC, Laticia Woodruff, RN, MSN, Candice Miller: University of Alabama at Birmingham; Joyce Carlone, RN, RNP, Karla Caylor, BSN, RN, Sharon Henderson, RN: Emory University; Diane Bresch, RN: University of North Carolina; Trisha Sturgill: Medical University of South Carolina; and Teresa Arb: Washington University.

We also gratefully acknowledge the following physicians who enrolled patients into the CLEAR Registry: Jacob Aelion, MD, Jackson, TN; Charles Bell, MD, Birmingham, AL; Sohrab Fallahi, MD, Montgomery, AL; Richard Jones, PhD, MD, Tuscaloosa, AL; Maura Kennedy, MD, Birmingham, AL; Adahli Estrada Massey, MD, Auburn, AL; John Morgan, MD, Birmingham, AL; Donna Paul, MD, Montgomery, AL; Runas Powers, MD, Alexander City, AL; William Shergy, MD, Huntsville, AL; Cornelius Thomas, MD, Birmingham, AL; Ben Wang, MD, Memphis, TN.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES