American Journal of Epidemiology Copyright © 2004 by the Johns Hopkins Bloomberg School of Public Health All rights reserved
Vol. 160, No. 5 Printed in U.S.A. DOI: 10.1093/aje/kwh245
Factors Associated with Treatment Initiation after Osteoporosis Screening
Renee M. Brennan1, Jean Wactawski-Wende1,2, Carlos J. Crespo1, and Jacek Dmochowski3 1
Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY. Department of Gynecology/Obstetrics, University at Buffalo, Buffalo, NY. 3 Department of Mathematics, University of North Carolina at Charlotte, Charlotte, NC. 2
Received for publication December 9, 2003; accepted for publication March 24, 2004.
bone density; densitometry; diagnosis; drug therapy; mass screening; osteoporosis, postmenopause; risk factors
Abbreviations: CI, confidence interval; DXA, dual-energy x-ray absorptiometry; OR, odds ratio.
Osteoporosis is characterized by low bone mass and is a progressive, systemic disease that leads to an increase in bone fragility and susceptibility to fracture (1). Osteoporosis is a major public health threat in the United States; approximately 44 million persons aged 50 years or older, including 30 million women, are affected by the disease (2). The number of persons at risk is increasing as the population ages. While the current economic impact is substantial, management of the disease will require increasing resources in the near future. Detection of osteoporosis is possible at treatable stages of the disease, and early detection and treatment have been shown to decrease associated morbidity and mortality (3). Dual-energy x-ray absorptiometry (DXA) is currently considered the “gold standard” for measuring bone mineral density and predicting fracture risk (4). Fracture risk is also
affected by other factors, such as poor bone quality and a propensity to fall, but bone density is the single best predictor of fracture risk. The US Food and Drug Administration has approved several treatments for the prevention and/or treatment of osteoporosis, including bisphosphonates (alendronate and risedronate), calcitonin, hormone therapy (estrogen alone or in combination with progestin), raloxifene, and teriparatide (5). Inadequate diagnosis and treatment of osteoporosis are a problem (6, 7). Previous studies have shown that providers recommend and women accept drug treatment more often when screening results show an increased risk of fracture (8– 12). These studies have focused on the outcomes of a screening test ordered by a physician. Some degree of awareness of the disease and potential interest in treatment are implied when a physician orders a test. The factors associ-
Correspondence to Renee M. Brennan, 65 Farber Hall, University at Buffalo, 3435 Main Street, Buffalo, NY 14214 (e-mail:
[email protected]).
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The prevalence of osteoporosis and factors associated with treatment initiation after detection of osteoporosis were determined for previously unscreened, postmenopausal women. Dual-energy x-ray absorptiometry screening was conducted in 1997–2000 as part of an ancillary study of the Buffalo, New York, center of the Women’s Health Initiative Observational Study. A total of 945 women were previously unaware of their bone density, although, for 344 (36.4%), osteoporosis was newly detected through screening (T-score ≤ –2.5). Of those women, 250 (72.7%) discussed the results with a health care provider, and 140 (56.0%) initiated treatment after doing so. In multivariate logistic regression analyses, factors associated with treatment initiation were T-score (odds ratio (OR) = 0.39 per unit increase, 95% confidence interval (CI): 0.23, 0.67), routine medical care more often than yearly (OR = 2.08, 95% CI: 1.12, 3.86), college education (OR = 2.58, 95% CI: 1.25, 5.31), family income of ≥$50,000 (OR = 2.06, 95% CI: 1.03, 4.14), and discussing screening results with a gynecologist (OR = 3.20, 95% CI: 1.33, 7.67). These findings suggest that many postmenopausal women are unaware of their bone density and could benefit from screening. In this study, approximately half of the women with osteoporosis initiated treatment after screening. Disease severity, medical care frequency, education, income, and physician type predicted treatment initiation.
476 Brennan et al.
ated with treatment following screening in an at-risk population not specifically referred by a physician have not been well documented. This study’s objectives were to determine the prevalence of osteoporosis in a previously unscreened group of postmenopausal women and, for women newly determined to have osteoporosis at screening, to assess factors associated with drug treatment initiation. MATERIALS AND METHODS
RESULTS
Of the 1,952 participants in the Women’s Health Initiative Observational Study eligible for the Osteoporosis and Oral Bone Loss Study, 1,468 (75.2 percent) agreed to take part. The remainder were either unable to be contacted (n = 111; 5.7 percent) or uninterested (n = 373; 19.1 percent). The response rate for the Osteoporosis and Oral Bone Loss Study follow-up questionnaire was 95.4 percent (n = 1,400). Of the respondents, 945 reported never being screened or diagnosed with osteoporosis or taking a bone drug other than hormone therapy prior to participation in this study. Baseline characteristics of these 945 participants are presented in table 1. Results of the DXA screening showed that 344 (36.4 percent) women previously unaware of their bone density status were newly determined to have osteoporosis according to World Health Organization criteria. A total of 250 (72.7 percent) of these participants reported discussing results with a health care provider, and 140 (56.0 percent) of those initiated drug treatment (figure 1). Am J Epidemiol 2004;160:475–483
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The study population comprised participants enrolled in the cross-sectional study, Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women, conducted from 1997 to 2000 as an ancillary study of the Buffalo, New York, center of the Women’s Health Initiative Observational Study. The Women’s Health Initiative is an ongoing clinical trial and observational prevention study of postmenopausal women, which is funded by the National Institutes of Health (13). This ancillary study was designed to assess the relation between bone density and periodontal disease. Inclusion criteria were observational study participation and at least six teeth in the mouth. Exclusion factors were known bone disease (other than osteoporosis), known aortic calcification, steroid dependency (use of steroids throughout the past 6 months or longer), and active cancer or cancer chemotherapy. Participants completed several questionnaires that included items on known risk factors for osteoporosis and periodontal disease. Bone densities of the spine, hip, forearm, and total body were measured by DXA (Hologic QDR-4500A; Hologic, Inc., Waltham, Massachusetts), and an oral health examination was completed. Participants were mailed a copy of their DXA results with a summary cover sheet, which included the World Health Organization definitions and values of T-scores for four measured sites (anteroposterior spine, lateral spine, femoral neck, and total forearm). The impact of this DXA screening on study participants was assessed by using a follow-up questionnaire. Participants were asked whether they discussed the DXA results with their health care provider, whether their provider recommended various treatments, whether they initiated any treatment, whether they were complying with treatment, and whether they personally decided to make any changes not recommended by their provider. Participants were mailed the questionnaires at least 1 year after they participated in the study (DXA screening) to allow ample time to discuss their DXA findings with their health care provider. A postagepaid envelope was included to return the completed questionnaires. Questionnaires not returned from the initial mailing were followed up with a second mailing, postcard reminders, and telephone follow-up. This study was approved by the Health Sciences Internal Review Board of the University at Buffalo. Informed consent was obtained for both the Women’s Health Initiative study and the Osteoporosis and Oral Bone Loss Study. Data collected from the follow-up questionnaire were combined with existing data from participants’ records of the Women’s Health Initiative Observational Study and the Osteoporosis and Oral Bone Loss Study to form the analyt-
ical data set. Since this study aimed to assess the impact of osteoporosis screening in a group of postmenopausal women unaware of their bone density status, participants who reported a previous diagnosis of osteoporosis, previous bone density testing, or ever taking a bone drug other than hormone therapy were excluded from the analyses. Descriptive statistics were computed for demographics and other variables and for outcomes of screening and discussion of results with a health care provider. Univariate logistic regression models were developed to establish factors associated with drug treatment initiation that were further analyzed in multivariate models. Factors assessed included age (years), T-score (lowest of the femoral neck, lateral spine, anteroposterior spine, and total forearm T-scores), body mass index (kilograms per meter squared), race (American Indian/Alaskan Native, Asian/Pacific Islander, Black/African American, Hispanic/Latino, or White), hormone therapy use (never, former, or current), frequency of routine medical care (yearly or less or more often than yearly), fracture history after 40 years of age (yes or no), family history of fracture (yes or no), smoking (ever or never), education (high school or less, college attendance/ graduation, or graduate school attendance/graduation), current employment (yes or no), income ( 0.05, was used to establish the final multivariate predictive model. The Statistical Package for the Social Sciences (SPSS), version 10.0 for Windows (SPSS, Inc., Chicago, Illinois), was utilized for all analyses.
Treatment Initiation after Osteoporosis Screening 477
TABLE 1. Baseline characteristics of newly screened postmenopausal women previously unaware of their bone density status (n = 945),* Buffalo, New York, 1997–2000 No. or mean (SD†)
Age (years)
72.2 (7.5)
DXA T-score value‡
–2.1 (1.2)
Body mass index (kg/m2)
27.0 (5.1)
%
Race American Indian/Alaskan Native
4
0.4
Asian/Pacific Islander
3
0.3
Black/African American
11
1.2
Hispanic/Latino
4
White
922
97.7
Never
326
34.5
Former
188
19.9
Current
431
45.6
Routine medical care (more often than yearly)
635
67.2
Fracture history after 40 years of age (yes)
288
30.5
Family history of fracture (yes)
347
37.2
Smoking (ever)
429
45.4
High school or less
219
23.6
College attendance/graduation
407
43.9
Graduate school attendance/graduation
302
32.5
Employment status (employed)
272
29.7
Income (≥$50,000)
320
35.8
Medical insurance (yes)
904
98.9
0.4
Hormone therapy use
* Race, n = 944; fracture history after 40 years of age, n = 943; family history of fracture, n = 934; education, n = 928; employment status, n = 915; income, n = 894; medical insurance, n = 914. † SD, standard deviation. ‡ Lowest T-score for the four sites measured by dual-energy x-ray absorptiometry (DXA): femoral neck, lateral spine, anteroposterior spine, and total forearm.
Table 2 presents baseline characteristics of the 250 osteoporotic women (T-score ≤ –2.5) who discussed their DXA results with their provider. Mean age was 75.5 (standard deviation, 6.6) years, and mean T-score was –3.3 (standard deviation, 0.6). Ninety-eight percent were White, and 25.6 percent were currently using hormone therapy. Most reported college or graduate school education, having medical insurance, and receiving routine medical care at least yearly. Univariate logistic regression results are presented in table 3. Women who initiated treatment were more likely to have a lower T-score (odds ratio (OR) per unit increase = 0.42, 95 percent confidence interval (CI): 0.26, 0.68), routine medical care more often than yearly (OR = 2.01, 95 percent CI: 1.16, 3.50) compared with yearly or less, a college (OR = 1.79, 95 percent CI: 0.96, 3.35) or graduate school (OR = 2.16, 95 percent CI: 1.08, 4.33) education compared with a high school education or less, a total family income of $50,000 or more (OR = 1.80, 95 percent CI: 0.98, 3.33), and discussion Am J Epidemiol 2004;160:475–483
of screening results with a gynecologist (OR = 2.85, 95 percent CI: 1.28, 6.30). In multivariate logistic regression analysis (table 4), factors independently associated with treatment initiation were lower T-score (OR per unit increase = 0.39, 95 percent CI: 0.23, 0.67), routine medical care more often than yearly (OR = 2.08, 95 percent CI: 1.12, 3.86) compared with yearly or less, a college education (OR = 2.58, 95 percent CI: 1.25, 5.31) compared with a high school education or less, a total family income of $50,000 or more (OR = 2.06, 95 percent CI: 1.03, 4.14), and discussion of screening results with a gynecologist (OR = 3.20, 95 percent CI: 1.33, 7.67). Because women who were currently receiving hormone therapy could be considered already being treated for osteoporosis, we repeated the analysis, including only those women not using hormone therapy at screening (n = 258). We found that results did not change appreciably. A total of 186 (72.1 percent) women discussed the results with their health care provider, and 103 (55.4 percent) of those women initiated treatment. Women not on hormone therapy who
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478 Brennan et al.
remained appreciably unchanged. Because of a reduced sample size in some instances, confidence intervals widened and resulted in fewer factors reaching statistical significance (data not presented). Similarly, because some providers may have been aware of the National Osteoporosis Foundation guidelines for treatment of osteoporosis, the logistic regression analyses were repeated by restricting them to participants who had a Tscore of –2.0 or less. According to National Osteoporosis Foundation guidelines, these participants should be considered for treatment (15). A total of 500 (52.9 percent) participants had T-scores of –2.0 or less, and 357 (71.4 percent) of those women discussed the results with their provider. The logistic regression findings for treatment initiation again did not differ appreciably (data not presented). Finally, the analysis was repeated by restricting it to Caucasian participants only, and our findings did not change (data not presented).
FIGURE 1. Selection of study participants and outcomes of osteoporosis screening, Buffalo, New York, 1997–2000.
initiated treatment were significantly more likely to have a lower T-score (OR per unit increase = 0.42, 95 percent CI: 0.23, 0.76) and routine medical care more often than yearly (OR = 2.22, 95 percent CI: 1.08, 4.53) compared with yearly or less (table 5). Although not statistically significant, point estimates for higher education, greater income, and gynecologist specialty did not differ appreciably from those presented in table 4. For the variable DXA T-score, the lowest value for the femoral neck, lateral spine, anteroposterior spine, and total forearm was used. These specific T-score values were reported on a summary cover sheet provided to each participant. Women were given a copy of the entire DXA report for each region measured. As such, each woman and her physician had T-score values for each of the sites measured as part of this research study. In a typical clinical setting, lateral spine values are not measured and reported. In fact, the International Society for Clinical Densitometry does not recommend using the lateral spine to diagnose osteoporosis (14). However, since the lateral values were reported, they were included in the analysis. To determine the impact of lateral values on the findings, we repeated the analysis without using lateral spine T-scores in our definition of osteoporosis. Restricting the analysis to the femoral neck, anteroposterior spine, and total forearm resulted in 14 percent fewer participants being defined as having osteoporosis. Regardless, the point estimates (odds ratios) in logistic regression analysis
Only one third of study questionnaire respondents had ever been screened for or were determined as being osteoporotic prior to having DXA as part of participation in this research study, but 91 percent of the same group met National Osteoporosis Foundation guidelines for screening (at risk for osteoporosis). The Foundation recommends that all women under the age of 65 years who have one or more additional risk factors for osteoporosis (in addition to being postmenopausal and female) and all women aged 65 years or older, regardless of additional risk factors, should have an osteoporosis screening test (15). Furthermore, for over one third of our study participants who reported never being screened previously, their bone density values met World Health Organization criteria for a diagnosis of osteoporosis (T-score ≤ –2.5). Although participants were volunteers from two epidemiologic studies, the prevalence of osteoporosis was similar to that in the Third National Health and Nutrition Examination Survey, a nationally representative sample of the US population (16). Extrapolating our study finding to estimate US population figures, we calculate that 22 million Caucasian women in this age group who meet National Osteoporosis Foundation screening guidelines may be unscreened for osteoporosis and that about 8 million of these women would have undiagnosed disease according to World Health Organization criteria. These calculations are based on a US population estimate of approximately 33 million Caucasian women in the same age range (52–90 years) as that in our study (17). These figures represent conservative population estimates and should be interpreted with caution since our study sample was not a representative, population-based sample. Nevertheless, our results do suggest that a large percentage of women at risk for fracture are currently unaware of their status because of the absence of screening for this condition. Of those women determined at screening to be osteoporotic, 27 percent did not discuss their DXA results with a health care provider. This rate of follow-up is lower than that determined in a previous study by Rubin and Cummings (8), which included a very high percentage of women who received a referral from their physician for Am J Epidemiol 2004;160:475–483
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DISCUSSION
Treatment Initiation after Osteoporosis Screening 479 TABLE 2. Baseline characteristics of postmenopausal women previously unaware of their bone density status whose T-score ≤ –2.5 at screening and who discussed their results with their health care provider (n = 250),* Buffalo, New York, 1997–2000 Total (n = 250, 100%) No. or mean (SD‡)
%
Initiated treatment (n = 140, 56.0%) No. or mean (SD)
%
Did not initiate treatment (n = 107, 42.8%)† No. or mean (SD)
Age (years)
75.5 (6.6)
75.8 (6.4)
75.4 (6.9)
DXA T-score value§
–3.3(0.6)
–3.4 (0.6)
–3.1 (0.5)
Body mass index (kg/m2)
25.7 (4.2)
25.3 (4.2)
26.1 (4.3)
%
Race Asian/Pacific Islander
2
0.8
2
1.4
0
0.0
Black/African American†
3
1.2
0
0.0
0
0.0
White
245
98.0
138
98.6
107
100.0
Never
114
45.6
67
47.9
47
43.9
Former
72
28.8
36
25.7
34
31.8
Current
64
25.6
37
26.4
26
24.3
Routine medical care (more often than yearly)
176
70.4
107
76.4
66
61.7
Fracture history after 40 years of age (yes)
99
39.8
62
44.3
36
34.0
Family history of fracture (yes)
95
38.3
53
38.1
41
38.7
Smoking (ever)
117
46.8
65
46.4
49
45.8
High school or less
63
25.2
28
20.1
35
32.7
College attendance/graduation
114
45.6
66
47.5
46
43.0
Graduate school attendance/graduation
72
28.8
45
32.4
26
24.3
Employment status (employed)
47
19.3
23
16.8
24
23.1
Income (≥$50,000)
62
26.5
41
31.1
20
20.0
Medical insurance (yes)
242
99.2
137
100.0
102
98.1
Visit date with provider¶ (after 1998)
172
70.2
92
66.7
79
76.0
Gender of provider (female)
84
33.6
47
33.6
35
32.7
Length of relationship with provider (no. of years)
9.9
(8.8)
9.7
(8.8)
10.3
(8.9)
Specialty of provider (gynecologist)
38
15.2
29
20.7
9
8.4
Hormone therapy use
* Total: fracture history after 40 years of age, n = 249; family history of fracture, n = 248; education, n = 249; employment status, n = 244; income, n = 234; medical insurance, n = 244; visit date with provider, n = 245; length of relationship with provider, n = 246. † Data were missing on treatment initiation for Black/African-American participants (n = 3). ‡ SD, standard deviation. § Lowest T-score for the four sites measured by dual-energy x-ray absorptiometry (DXA): femoral neck, lateral spine, anteroposterior spine, and total forearm. ¶ Health care provider/physician.
screening. This difference in follow-up is likely attributable to the difference in study design; our study involved community-like screening without referral from a physician. Community-based screening tests are effective only if they influence clinical decisions, and an important consideration should be a mechanism to ensure that women discuss screening results with their provider. It is an important public health finding that even within this group of healthy, well-educated, and self-selected women, a large percentage were previously unaware of their bone density status and were newly diagnosed with osteoporosis. Over half of those women determined as having osteoporosis who consulted their health care provider Am J Epidemiol 2004;160:475–483
after screening initiated treatment, a notable percentage initiating treatment for a disease that may not have been detected without the study DXA screening. However, almost half of the osteoporotic women did not initiate treatment. Decisions regarding initiation of treatment after diagnosis are multifactorial and may be influenced by risk factors for osteoporosis and related fracture other than low bone density. Physician recommendation and patient acceptance of treatment are also important in decision making and may be influenced by the perceived effectiveness of osteoporosis drug treatments or side effects, costs, expected uptake of treatment, or agreement with treatment recommendations.
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480 Brennan et al.
TABLE 3. Univariate predictors of drug treatment initiation for postmenopausal women previously unaware of their bone density status whose T-score ≤ –2.5 at screening and who discussed their results with their health care provider (n = 247),* Buffalo, New York, 1997–2000 Unadjusted OR†
95% CI†
p value
Age (per year increase)
1.01
0.97, 1.05
0.637
DXA T-score value‡ (per unit increase)
0.42
0.26, 0.68
