The near absence of osteoporosis treatment in older men with fractures
(几乎所有老年男性的骨折患者存在骨质疏松症漏治现象)

Osteoporosis International

Adrianne C. Feldstein^{1, 3}, Gregory Nichols¹, Eric Orwoll², Patricia J. Elmer¹, David H. Smith¹, Michael Herson³ and Mikel Aickin¹

Received: 5 February 2004  Accepted: 10 June 2004  Published online: 1 June 2005

Abstract  The burden of osteoporotic fractures in older men is significant. The objectives of our study were to: (1) characterize older men with fractures associated with osteoporosis, (2) determine if medication treatment rates for osteoporosis are improving and (3) identify patient, healthcare benefit and utilization, and clinician characteristics that are significantly associated with treatment. This retrospective cohort study assessed 1,171 men aged 65 or older with any new fracture associated with osteoporosis between 1 January 1998 and 30 June 2001 in a non-profit health maintenance organization in the United States. Multiple logistic regression was used to evaluate pre-fracture factors for their association with osteoporosis treatment in the 6-month post-fracture period. The main outcome measure was pharmacologic treatment for osteoporosis in the 6 months after the index fracture. Subjects average age was 76.7 years; 3.3% had a diagnosis of osteoporosis and 15.2% a diagnosis or medication associated with secondary osteoporosis. Only 7.1% of the study population and 16.0% of those with a hip or vertebral fracture received a medication for osteoporosis following the index fracture, and treatment rates did not improve over time. In the multivariate model, factors significantly associated with drug treatment were a higher value on the Charlson Comorbidity Index (odds ratio 1.26, 95% confidence interval 1.05–1.51), having an osteoporosis diagnosis (odds ratio 8.11, 95% confidence interval 3.08–21.3), chronic glucocorticoid use (odds ratio 5.37, 95% confidence interval 2.37–12.2) and a vertebral fracture (odds ratio 16.6, 95% confidence interval 7.8–31.4). Bone mineral density measurement was rare ( n =13, 1.1%). Our findings suggest that there is under-ascertainment and under-treatment of osteoporosis and modifiable secondary causes in older men with fractures. Information systems merging diagnostic and treatment information can help delineate gaps in patient management. Interventions showing promise in other conditions should be evaluated to improve care for osteoporosis.

Keywords  Bone mineral density - Men - Osteoporosis medication

Introduction

Although osteoporosis is often considered a woman s disease, the risk and burden of osteoporotic fractures in older men are substantial, and the consequences of a hip fracture may be more severe for a man than a woman [1, 2]. The lifetime risk of any clinical osteoporotic fracture of the hip, wrist or vertebra in white men is 13%, compared to 40% in women [3, 4, 5], and 30% of hip fractures occur in men [6]. Men and women who have sustained a hip fracture are 3–5 times more likely to die in the 12 months after the fracture than those who have not had a fracture [7]. Men have a 70–100% higher mortality rate than women after hip fracture [2, 8, 9]. Osteoporotic fractures, particularly those of the hip, result in significant disability, medical care costs and reduction in quality of life [3, 10]. The numbers of hip fractures are projected to quadruple by 2050, and the effects of osteoporosis will become an increasing human and healthcare system burden [1].

Expert consensus for the evaluation and treatment of osteoporosis in men after a hip fracture includes an evaluation for secondary causes of osteoporosis, bone mineral density (BMD) measurement, calcium and vitamin D supplementation, and a bisphosphonate medication [11]. Although there are effective and approved treatments for osteoporosis in men, the condition is rarely recognized and treated, even after a fracture has occurred [9, 12]. We found that in men aged 65–89 who had sustained a study fracture (any except skull, facial, finger, toe or ankle) during 1998–1999, only 1% received a BMD measurement and 3% a pharmacologic treatment for osteoporosis during the 2 years [12]. We were unable to identify other papers specific to men describing the patient characteristics relevant to risk and treatment, treatment trends and factors associated with treatment across a broad range of fracture types.

We undertook the current study to characterize older men with any fracture associated with osteoporosis and to determine if the pharmacologic treatment of osteoporosis in men after a fracture has improved since the publication of information on the consensus of experts [11], and the availability and FDA approval of effective treatment. We also sought to determine the patient, healthcare benefit and utilization, and clinician characteristics that are significantly associated with treatment. The results should help to inform future interventions.

Materials and methods

Selected details of the study methods have been described previously [13].

Research setting

The study site was a not-for-profit HMO with about 440,000 members in the Northwestern United States. The HMO s clinical electronic databases capture close to 100% of all medical care and pharmacy services received by members. The electronic medical record contains clinician-entered ICD-9-CM-coded diagnoses and problem list. These databases are linked through the unique health record number that each member receives at the time of his or her first enrollment in the health plan.

Clinicians have access to the HMO s intranet-based clinical guidelines for osteoporosis, which are consistent with prevailing national guidelines and began to include post-fracture management of osteoporosis in men in January of 2001. Clinicians use of national guidelines available on the Internet is voluntary [14, 15, 16, 17, 18, 19].

Study subjects

The study was approved by the HMO s Institutional Review Board; members provide consent for use of their records for research purposes. Study participants were male members of the HMO who had a new study-defined ICD-9-CM fracture diagnosis and were aged 65 or older at the time of the fracture ( n =1, 526).

Study-defined fractures included any closed fracture except skull, facial, finger, toe or ankle that was coded as a diagnosis during a clinical encounter. We did not include open fractures (suggestive of high force). The study-defined fractures have been associated with decreased bone mass [20].

We defined the index date as the date of the clinical encounter during which the fracture was diagnosed. We included only those men who had minimum HMO eligibility for 12 months before and 6 months after the index date ( n =1, 195). This included the exclusion of 203 men who died within 6 months after the index fracture. We excluded those who did not have a pharmacy benefit at the time of the index fracture, resulting in a final study population of 1,171 men.

Analysis variables

We grouped index fractures according to site—hip, vertebra, wrist, humerus, pelvis, other upper extremity (radius, ulna, carpals and metacarpals), other lower extremity (femur, patella, tibia, fibula, tarsals and metatarsals) and other torso (rib or clavicle). For each study subject, we identified an 18-month observation window, beginning 12 months prior to and ending 6 months following the index date. We used a 12-month pre-fracture period to assess medication use and other healthcare utilization, and the 6-month post-fracture period to assess patient management in response to the fracture. We also used at least the 12-month pre-fracture period (all available data from 1 January 1997 through the index fracture) to assess for clinical conditions associated with osteoporosis, fracture risk and the presence of other chronic conditions. We limited our post-fracture evaluation window to 6 months because we were interested in practice patterns in response to a fracture. After about 6 months, other triggers for treatment could intervene, such as additional fractures and visible kyphosis.

We defined use of pharmacologic agents for the treatment of primary osteoporosis as a dispensed prescription for oral bisphosphonates or calcitonin. We did not include treatment of secondary osteoporosis, such as testosterone for hypogonadism. We defined existing treatment as a dispensed prescription for any of these drugs prior to the patient index date. New treatment, the primary outcome for analysis, was defined as a dispensed prescription that occurred in the post-fracture period without a dispensed prescription in the pre-fracture period.

BMD measurements were performed by an outside contractor that provided rapid patient access to axial dual X-ray absorptiometry (DXA) and electronic results. We recorded any BMD measurement during the 18-month observation period. BMD is not typically measured frequently; a BMD measurement frequency of 1–2 years is recommended by prevailing clinical guidelines [21].

Pre-fracture comorbidities were identified by searching visit diagnoses and problem list notations in the ambulatory medical record from 1 January 1997, through the date of the index fracture. We were interested in whether or not patient disease burden was associated with treatment for osteoporosis. We included common co-morbidities (diabetes, heart disease, hypertension, hyperlipidemia, malignant neoplasms, COPD/asthma, arthropathies, osteoarthritis and depressive disorders). We used the identified comorbidities to calculate the Charlson Comorbidity Index [22] as adapted for use with ICD-9-CM administrative databases [23].

We were also interested in whether or not patient risk factors for osteoporotic fracture were associated with treatment. To this end, we calculated age on the date of the index fracture and averaged body weight over the entire observation period. We also identified specific diagnoses associated with secondary osteoporosis (hyperthyroidism, hyperparathyroidism, Cushing s syndrome, vitamin D deficiency, cirrhosis, chronic renal failure, malabsorption, malnutrition, testicular hypofunction and hypogonadism) and conditions associated with risk of fracture due to falls (Parkinson s disease, rheumatoid arthritis, osteoarthritis, Alzheimers, senility and subacute delirium, alcoholism and type 1 diabetes). We examined use of medications prior to the index fracture that are related to the development of osteoporosis. Anti-convulsant drug use, associated with osteomalacia [24], was defined as any single dispensed prescription for phenobarbital, phenytoin or carbamazepine. In accordance with accepted guidelines [18], chronic glucocorticoid use was defined as usage in excess of 5 mg of prednisone or its equivalent per day for more than 90 days prior to the index fracture. We also examined medications related to increased risk of falls and fractures, including long-acting benzodiazepines (chlordiazepoxide, diazepam, flurazepam, triazolam) and tertiary tricyclic antidepressants (amitriptyline, imipramine, doxepin) [21] that were in use at the time of the index fracture. We considered a patient to be a user of these medications at the time of the index fracture if the date the prescription was dispensed plus the days of medication supplied included the index fracture date.

We also evaluated healthcare benefit, patient medical utilization and clinician characteristics for their potential association with receipt of an osteoporosis medication. We hypothesized that high out-of-pocket expenses for care could be associated with lack of treatment. We assessed healthcare benefit variables at the time of the index fracture, including the copayment level for office visits and for filled prescriptions dichotomized into high ($20 or more) and low. We assessed utilization variables in the 12-month pre-fracture period because we were interested in whether the type or frequency of interaction with the healthcare system was associated with treatment. We included whether or not the patient had an office visit for a routine examination; counts of visits to the patient s personal primary care clinician; visits to any primary care clinician (internal medicine or family practice physicians, nurse practitioners or physician assistants); emergency room visits; hospital admissions; days spent in skilled nursing, intermediate or residential care facilities. We hypothesized that some types of clinicians might be more apt to treat than others. Clinician characteristics were assessed at the time of the index fracture and included the age and gender of the patient s primary care clinician, whether that clinician was an MD or non-MD (nurse practitioner or physician assistant), the total number of patients on the clinician s panel and the average number of monthly visits to the clinician.

Statistical methods

All analyses were performed using SAS version 6.12 (SAS Institute, Cary, N.C.). We conducted bivariate comparisons using Student s t -test for continuous measures and Pearson s chi-square tests for dichotomous or categorical variables. We used the Mantel-Haenszel chi-square to test trends across index years.

We evaluated 34 potential explanatory variables for their ability to predict receipt of a drug for the treatment of osteoporosis in the follow-up period, limiting the analysis to the 1,143 men who had not received an osteoporosis drug prior to their index fracture. The variables tested included patient clinical characteristics, patient utilization and health benefit variables, primary care clinician characteristics and three interaction terms (age with osteoporosis diagnosis, age with number of ambulatory visits and osteoporosis diagnosis with chronic steroid use). Using the backward selection stepwise option and a 0.05 P -value criterion, we reduced these 34 possible predictor variables to the four-variable model presented here (results for the 30 nonsignificant variables are shown in the Appendix).

Results

Table 1 shows that the mean age of study subjects was 76.7±7.6 years, and body weight was 179±34 pounds. BMD measurement was rare ( n =13, 1.1%). There were 39 patients (3.3%) with a diagnosis of osteoporosis, 178 patients (15.2%) who had a diagnosis or were taking a medication associated with secondary osteoporosis and 484 patients (41.3%) with a diagnosis or medication associated with falls. The most common comorbidities were hypertension ( n =452, 38.6%), heart disease ( n =381, 32.5%), arthropathies ( n =374, 31.9%), and asthma/COPD ( n =327, 27.9%).

Table 1  Study population by post-fracture treatment status

⁺Includes hyperthyroidism (0.6%), hyperparathyroidism (0.3%), Cushing s syndrome (0.2%), cirrhosis (0.5%), chronic renal failure (5.3%) and testicular hypofunction (0.5%)

⁺⁺Includes Parkinson s (3.8%), rheumatoid arthritis (2.0%), osteoarthritis (18.1%), dementia (5.7%), alcoholism (2.6%), type 1 diabetes (2.9%) and stroke (13.3%). Note: These figures are not additive because the percentages are not mutually exclusive. *P<0.001, **P<0.05

Pharmacologic treatment of osteoporosis was uncommon—only 83 (7.1%) of the study population received one or more dispensed prescriptions following the index fracture. Nearly a quarter of these patients were already being treated prior to the fracture, i.e., only 63 (5.4%) received new treatment. In the bivariate analyses, factors strongly associated with receiving a drug after fracture included having received pre-fracture treatment (24.1% vs. 0.7%, P <0.001), having had a BMD measurement (5% vs. 0.8%, P <0.001), lower body weight (164 vs. 180 pounds, P <0.001), having received an osteoporosis diagnosis (28% vs. 1.5%, P <0.001), and chronic glucocorticoid use (24% vs. 3.9%, P <0.001). Men receiving a drug were also older (78.7 vs. 76.6 years, P =0.013) and less healthy, as evidenced by a higher score on the Charlson Comorbidity Index (1.8 vs. 1.3, P =0.005). Patients in the treated group were more likely to have malignant neoplasms (36% vs. 22.6%, P =0.005) and asthma/COPD (40% vs. 27.0%, P =0.013) than those who were not treated.

Table 2 shows the number of fractures by fracture site and the proportion of subjects with each fracture type who received post-fracture osteoporosis medication, BMD measurement and a pre-fracture diagnosis of osteoporosis, secondary osteoporosis or falls risk. The most common type of fracture was other torso (rib or clavicle) with 310 (26.5%), followed by vertebral ( n =204, 17.4%), hip ( n =203, 17.3%) and other lower extremity ( n =200, 17.1%). Although only 7.1% of all subjects received an osteoporosis medication following their fracture, 29.4% ( n =60) of the 204 subjects who had a vertebral fracture received post-fracture treatment. Only 5 of 203 (2.5%) of the men who had a hip fracture received an osteoporosis medication following their fracture. As noted, BMD measurement was rare overall and remained rare for all fracture types. Fractures most frequently associated with an osteoporosis diagnosis were vertebral fractures (11.8%), and those most frequently associated with a diagnosis increasing the risk for secondary osteoporosis or a diagnosis increasing the risk of falls were hip fractures (12.3% and 56.2%, respectively).

Table 2  Number (%) with post-fracture osteoporosis drug treatment, BMD measurement* and relevant diagnoses by Index Fracture Site

*BMD measurement in the window 12 months prior to and 6 months after index fracture

We also compared the distribution of fractures in those who did and did not receive an osteoporosis medication and/or a BMD measurement. Most (72.3%) of the 83 subjects who received a drug had vertebral fractures. Of the 13 subjects who had a BMD measurement, 6 (46.2%) had vertebral fractures, 3 (23.1%) had hip fractures, 2 (15.4%) had other torso fractures, and one each (7.7%) had a wrist fracture or other lower extremity fracture. Four (30.8%) had osteoporosis and 8 (61.5%) had osteopenia at any site, while only 1 (7.7%) had normal bone mass. In univariate comparisons, patients who had not received a post-fracture osteoporosis medication were significantly more likely than those who did have such treatment to have had fractures of hip (18.2% vs. 6.0%; P <0.001), other upper extremity (9.9% vs.1.2%; P <0.05), other lower extremity (18.2% vs. 2.4%; P <0.001) or other torso (27.6% vs. 12.1%; P <0.001). Patients who had received an osteoporosis medication or a BMD measurement were more likely than those who had not (72.3% vs. 13.2%; P <0.001 and 46.2% vs. 17.1%; P <0.05) to have had a vertebral fracture.

Figure 1 displays the proportion of study subjects who received a BMD measurement and who received new or ongoing pharmacotherapy for osteoporosis by year of index fracture. Although these proportions were relatively stable (the test for trend was not significant), new drug treatment appeared greater in 2001 than in prior years. New drug treatment in men with a hip or vertebral fracture (not displayed) also appeared to improve from 12.7% in 1998 to 18.6% in 2001, although this was also not significant. Figure 2 shows post-fracture pharmacologic treatment by type of treatment, by index year. Calcitonin was the osteoporosis treatment of choice in 1998 and 1999, but bisphosphonates became more common in 2000, and significantly ( P =0.018) more common in 2001.

Fig. 1  Post-fracture treatment, by year of index fracture

Fig. 2  Post-fracture pharmacological treatment by year of index fracture

Table 3 displays the results of the multivariate logistic regression model predicting new osteoporosis medication use after the index fracture. Of the 34 variables tested in the stepwise fashion, only 4 provided statistically significant predictive value: a higher value on the Charlson Comorbidity Index (OR 1.26, 95% CI 1.05–1.51), an osteoporosis diagnosis (OR 8.11, 95% CI 3.08–21.3), chronic glucocorticoid use (OR 5.37, 95% CI 2.37–12.2) and a vertebral fracture (OR 16.6, 95% CI 7.8–31.4). Individual co-morbidities, those associated with secondary osteoporosis or falls, measures of utilization and healthcare benefit and clinician characteristics did not provide significant predictive value for new osteoporosis medication use.

Table 3  Multivariate logistic regression predicting post-fracture osteoporosis drug treatment in subjects without pre-fracture treatment (n=1, 143)

Discussion

We evaluated patient characteristics and trends in osteoporosis treatment after a fracture in men aged 65 and old