Diagnosis and Treatment of Osteoporosis in Postmenopausal Women With Distal Radius Fracture in Germany

By Endres, Heinz G Dasch, Burkhard; Maier, Christoph; Lungenhausen, Margitta; Smektala, Rudiger; Trampisch, Hans J; Pientka, Ludger

Key words: Distal radius fracture – Osteoporosis risk factors – Osteoporosis therapy Postmenopausal osteoporosis ABSTRACT

Objective: The aim of this study was to evaluate osteoporosis diagnosis and treatment on the basis of medical history, at hospital discharge, and 6-12 months after discharge, as well as to assess the frequency of subsequent fractures in postmenopausal women with distal radius fracture.

Research design and methods: A prospective, observational study of hospitalized women aged 55 years and older with an isolated distal radius fracture from minimal trauma. Subjects were recruited in 242 acute care hospitals in Germany.

Outcome measures: Potential risk factors for osteoporosis, frequency of osteoporosis assessment, frequency of medication treatment and subsequent fractures 6-12 months after discharge.

Results: Among 2031 patients we identified 652 appropriate postmenopausal women. Less than one-third of patient histories contained any bone density parameters, and only a minority of subjects (33%, 217) underwent bone density assessment while in hospital. Of these, 55% (119) were diagnosed with low bone density, yet only 30% of those were prescribed supplements (calcium/vitamin D) and/or specific osteoporosis medication (mostly bisphosphonates) at discharge. Six to twelve months after hospital discharge, the low rate of treatment had not changed substantially. In the interval, 4.3% had sustained a subsequent fracture from minimal trauma: 1.4% a distal radius fracture (0.3% a refracture) and 2.9% a hip joint or other fracture (not specified). A significant age difference between those with and without subsequent distal radius fractures was found (p = 0.01) but not a significant difference between patients with or without osteoporosis medication (p = 0.79), primarily because the case numbers were too small.

Conclusions: A substantial proportion of postmenopausal women hospitalized with distal radius fracture were not sufficiently evaluated or treated for their potential risk of osteoporosis.

Introduction

Osteoporosis represents a major public health problem, particularly in older women. The disease is characterized by bone fragility due to low bone mass and alterations of the bone microarchitecture. The main consequence of osteoporosis is an increased incidence of skeletal fractures, typically located at the hip or spine, resulting from low-energy trauma. At age 50 the lifetime risk of hip fracture and vertebral fracture for women is 17.5 and 16.0%, respectively’. The management of osteoporosis has improved in the past 10 years with the availability of new drugs with proved efficacy against fractures. Choice of treatment depends on the fracture risk and its determinants (e.g., age, bone mineral density, prevalent fractures)2,3.

Distal radius fracture has been shown to be associated with an increased risk of further fractures4,5. Interestingly, the incidence of distal radius fracture starts to rise approximately 15 years earlier than that of hip fracture; thus, a distal radius fracture is a potential marker of imminent hip fracture. Therefore, elderly patients with distal radius fracture resulting from lowenergy trauma constitute a high-risk group, and ideal candidates for secondary prevention including further assessment and treatment of osteoporosis and fall risk. The purpose of the present study, therefore, was to evaluate the diagnosis and treatment of osteoporosis in daily practice in Germany, specifically as it relates to postmenopausal women who have sustained a distal radius fracture due to low-energy trauma.

Patients and methods

The present analysis was part of a large prospective observational study described previously6. Briefly, more than 16000 inpatients with hip or forearm fractures were recruited in 423 clinics and hospitals (242 acutecare (57%) and 195 rehabilitation facilities (43%)) from all regions of Germany between January 2002 and September 2003. Total enrolment of patients with forearm fractures was 2031. All of the patients in the latter group were recruited in acute-care facilities.

Subjects

The present analysis focuses on postmenopausal women aged 55 years and older who sustained an isolated low-energy fracture of the distal radius. Postmenopausal women were selected because they are much more likely to have osteoporosis, and because most of the evidence regarding the effectiveness of osteoporosis treatment has been derived from studies of women. The minimum age was set at 55 because the average age of menopause is 50, with 98.5% of women having experienced menopause by the age of 55(7). Exclusion criteria were fa) fracture not resulting from minimal trauma, ( b) pathologic fracture due to malignancy, (c) age under 55, or (d) unwillingness to take part in a telephone interview 6-12 months after discharge. Patients with missing data concerning the circumstances of the accident were also excluded. On the basis of these criteria, we identified 652 eligible patients.

The recruitment and research protocols were reviewed and approved by the ethics committee of the Bavarian State Medical Association and the study was undertaken in accordance with the Declaration of Helsinki. All subjects gave written, informed consent.

Physician questionnaire

Demographic characteristics, medical history, comorbidity, ASA classification (American Society of Anesthesiologists rating of operative risk), lifestyle factors such as past and present tobacco use, cause and site of the fracture, medical procedures (surgical, laboratory, radiology) and other aspects of medical care were obtained by the responsible physician. Women were asked whether they had fallen at least once during the past 3 months to define them as fallers. Established factors that contribute to an increased risk of falls were assessed. All subjects were asked about risk factors for primary osteoporosis, including prior diagnosis of low bone mineral density (BMD), previous history of minimal-trauma vertebral or hip fractures, physical immobility (over a period of more than 6 months), underweight (body mass index < 18kg/m2), height reduction (more than 4 cm height loss in the last 20 years), maternal history of fracture, and early onset of menopause (before the age of 45). Information was also collected about total calcium/vitamin D intake and prescription of specific osteoporosis drugs bisphosphonates, hormone replacement therapy, SERM (selective estrogen receptor modulators: raloxifene), or calcitonin - at the time of hospital admission and discharge. Differences in the rates of prescription between these two time periods were analyzed.

Follow-up telephone interview

All 652 patients who consented to participate in a follow-up survey were contacted by telephone 6-12 months after hospital discharge. No proxy interviews were conducted. A standardized questionnaire designed to elicit further patient information, including treatment data, was used. The main events of interest were the occurrence of skeletal fractures resulting from minimal trauma subsequent to hospital discharge, and osteoporosis medication.

Statistical analysis

Frequency distributions of baseline demographic and clinical characteristics were tabulated. A risk factor assessment for falls was made for patients classified as fallers or non-fallers. The frequency of osteoporosis risk factors as well as the frequency of prescriptions for osteoporosis medication were determined. We looked for differences in osteoporosis medication usage between the time of hospital admission, discharge and telephone interview, respectively. In addition, analyses were performed to determine whether the use of osteoporosis medication at the time of hospital discharge was related to occurrence of subsequent post-discharge fractures. Data analyses were primarily descriptive. Differences in proportion were tested with the Fisher’s exact test or chi-square test. All analyses were performed using the Statistical Analysis System (SAS, version 9.1.3).

Table 1. Characteristics of postmenopausal women with isolated distal radius fracture

Results

Baseline characteristics

Demographic and clinical characteristics of study subjects are shown in Table 1. The mean age was 70 years, and the majority of fractures (68.4%) occurred in women older than 65 years. Of the 652 subjects, 84.3% were classified as ASA I or II, 14.4% as ASA III and 1.2% as ASA IV or V. Twenty-four (3.7%) had a previous history of myocardial infarction, and 30 (4.6%) a history of stroke or transient ischemie attack. In 58.2% BMI was >/=25, in 17.6% it was >/ =30. Approximately 89% received operative treatment of the fracture, the remaining 11 % were treated conservatively.

Fallers

As shown in Table 2, more than half of subjects (51.5%) had suffered at least one fall during the 3 months prior to the fracture event that led to hospital. There was no significant difference between younger (< 70 years) and older (70+) with regard to frequency of previous falls (p = 0.21). Balance problems or dizziness, visual impairment, need for assistive walking devices, a history of arrhythmias, diagnosis of Parkinson's disease and the use of psychotropic drugs were significantly more common in women with a history of falls (p < 0.02) than in women without previous falls (data not shown). Also a history of stroke/transient ischemie attack was more frequent in fallers compared to nonfallers, but the number of cases was not large enough to show a statistically significant difference. Table 2. Risk factors for osteoporosis stratified by age

Assessment of risk factors for primary osteoporosis

Table 2 presents the prevalence of risk factors for primary osteoporosis, assessed at the time of hospital admission. Nearly 80% (517) of postmenopausal women in our study had at least one of the osteoporosis risk factors shown in Table 2. Of subjects for whom data on the following specific risk factors were available, 31 % had a prior diagnosis of low bone mineral density [BMD < -1 SD), 34% had previously sustained at least one fracture from low-energy trauma (radius fracture in about half of these cases), 41 % had lost > 4 cm of height in the last 20 years, 17% had experienced onset of menopause before age 45, and 14% reported a maternal history of fractures. The frequency of fractures increases significantly with age (p < 0.001), particularly fractures of the femoral neck, vertebrae and humerus.

Diagnosis of osteopenia/osteoporosis

In two-thirds (435 of 652) of subjects, no bone density diagnosis was performed during their stay in hospital. In almost half of the subjects (312 of 652) bone density status remained unknown, since the patient history contained no information in this regard. Only a third (217) underwent bone density diagnosis in hospital (Table 2). Osteopenia was diagnosed in 25 (11.5%) patients and osteoporosis in 94 (43.3%), with a significant difference by age classes. Reduced bone density was found in 45% of those < 70 years, but in 66% of those 70 or older. In most cases in which a bone density diagnosis was recorded, the diagnostic method was not specified (192). It is likely, however, that in most of these cases the assessment was by means of dual energy X-ray absorptiometry (DEXA).

For one-third (212) of subjects, the patient history did contain data on bone density. In 89 of these cases the diagnosis was verified in hospital (Table 3). In 41 % (20) of the 49 patients whose records indicated 'no bone density reduction', this information had to be corrected to osteopenia (9) or osteoporosis (11). In all 40 of the cases in which the records indicated the presence of osteopenia/osteoporosis, on the other hand, verification confirmed the diagnosis: five cases of osteopenia and 35 cases of osteoporosis.

For two-thirds (440) of subjects, the patient history contained no data on bone density. Verification of the status of 128 of these subjects showed normal bone density in 54% (69), and reduced bone density in 46% (59): 11 cases of osteopenia and 48 cases of osteoporosis.

Treatment of osteoporosis

Table 4 shows the proportion of patients receiving medical treatment for osteoporosis. At the time of hospital admission, 103 (15.8%) subjects were taking any osteoporosis medication. No age differences were found for this global variable. However, if the variables are considered individually, younger women, as would be expected, took estrogen more frequently than older ones [p = 0.003), although the overall proportion was small (5.1% of all subjects). This percentage was further reduced during stay in hospital to 2.5%. Use of bisphosphonates, on the other hand, increased significantly (from 1.7 to 6.3%, p < 0.001), while calcium/vitamin D supplementation declined moderately (from 11.5 to 9.4%, p = 0.24).

Table 3. Verification of patient history data on bone density

Even when osteopenia/osteoporosis had been previously diagnosed, only a minority (46%) of those diagnosed were regularly taking osteoporosis medication of any kind at time of admission (Table 5). Although in-hospital diagnoses increased the number of known cases of osteopenia/osteoporosis from 79 to 144, there was no improvement in medical treatment as regards osteoporosis medication. At time of discharge, only 30% of patients with proven bone density reduction were taking osteoporosis medication, and at the time of the interview the percentage had shrunk to 21 % (Table 5).

Osteoporosis medications at admission and at discharge included only a marginal rate of calcitonin but not raloxifene. Six to twelve months after hospital discharge this situation had not changed substantially, although four more patients were now taking raloxifene (Table 6). Notably, the use of estrogen declined to a tiny minority of 3 (0.5%).

Other treatments

Use of benzodiazepines and antidepressants also declined significantly over the course of hospital stay - that of antidepressants most markedly (from 4.5% of subjects to 0.8%; p < 0.001). In contrast to estrogen, however, use of psychopharmaceuticals returned almost to the initial values in the first 6-12 months after discharge. At discharge, a large percentage of subjects were supplied with analgesics, as would be expected, with rate of use decreasing noticeably up to the time of the interview. Nevertheless, 15% of subjects were still taking analgesics at that point.

Table 4. Medication at time of admission and discharge

Table 5. Osteoporosis medication by bone density status

Table 6. Medication at discharge and 6-12 months after discharge

Subsequent fractures after hospital discharge

Of the 652 patients who participated in the follow-up interviews 6-12 months after hospital discharge, 28 (4.3%) had experienced a subsequent fracture from minimal trauma. These fractures were nine distal radius fractures (six on the left side) and 21 hip joint or fractures at other locations (not specified). Of the nine patients with distal radius fracture, two (22%) had suffered a refracture at the same location (in both cases the left forearm), and two a combination fracture (forearm and other body part). A significant age difference was found only for the distal radius fractures (p = 0.014), which were more likely to occur in the older age group (70+).

Of those who were prescribed any osteoporosis medication at the time of discharge (M = 98), three (3.1%) suffered a subsequent fracture. Twenty-five cases of subsequent fractures, including the two subjects with combination fractures, occurred in patients not receiving osteoporosis medication at discharge (4.5% of 554). However, the differences in event rates between patients with or without osteoporosis medication were not statistically significant (p = 0.79).

Discussion

As a consequence of the aging of many Western populations, aging- related problems like the increasing incidence of osteoporotic fractures are becoming major issues8. A low-energy fracture of the distal radius is often the first sign of osteoporosis, particularly in the case of type I (postmenopausal) osteoporosis. About 50% of postmenopausal women with this kind of fracture have been shown to have evidence of osteoporosis at the distal radius, spine or hip9. A distal radius fracture has also been shown to be associated with an increased risk of subsequent osteoporotic fractures4'5. Therefore we focused on hospitalized postmenopausal women aged 55 and older who had sustained an isolated distal radius fracture from minimal trauma, and studied the treatment these patients received during their stay in hospital and afterwards.

The first sobering finding is that two-thirds of these patients did not undergo bone density diagnosis while in hospital. This means that, in about 50% of cases, bone density status remained unknown, since in a large proportion of cases the patient's medical history also lacked any information on bone density status. The second sobering finding is that, despite the diagnosis of 79 additional cases of osteopenia/osteoporosis, the rate of treatment with osteoporosis medication did not improve during hospitalization, but actually worsened significantly from 46 to 30% of the known cases of osteopenia/osteoporosis (p = 0.02). By the time of the interview, only 21% of known cases were still being treated with osteoporosis medication (Table 5).

Both results are surprising. From large observational studies we know that roughly 50% of postmenopausal women will suffer bone density loss (osteopenia or osteoporosis)10, and that the condition is more common in women like those in our study who have already suffered a distal radius fracture from low-energy trauma.

Therefore it is not surprising that in our study reduced bone density was found in 55% of patients who underwent a bone density assessment during their stay in hospital (Table 2). Among those patients aged 70 and older, bone density loss was found in two- thirds of the women assessed, reflecting the fact that in older women type I (postmenopausal) and type II (senile) osteoporosis can occur together.

Yet another sobering finding of our study is that data contained in the patient history indicating absence of bone density loss were not reliable. While diagnoses of bone density reduction was confirmed in 100% of cases by bone density measurements performed in hospital, diagnoses indicating no bone density loss were confirmed by in-hospital assessments in only 59% of cases (Table 3). In other words, more than 40% of all patients were incorrectly assessed as having normal bone density. Among patients whose medical history indicated unknown bone density status, almost half of those assessed in hospital were diagnosed with osteopenia/osteoporosis.

These results show that bone density testing should be performed on postmenopausal women with distal radius fractures resulting from a low-energy trauma, and that the appropriate medication should be prescribed. Postmenopausal women are perfect candidates for secondary prevention, particularly since there is good evidence that pharmacological treatment is effective in preventing skeletal fracture2'3'11. Nevertheless, at time of admission only 16% of subjects were taking any kind of osteoporosis medication. At discharge, the percentage had shrunk to 15% and by the time of the interview, 6-12 months after discharge, to 12% (Table 4, 6), even though nearly 80% of all patients had at least one risk factor for osteoporosis (Table 2). This decline in the percentage of patients taking osteoporosis medications was due mostly to patients who were first diagnosed with bone density loss during their stay in hospital not taking supplements at the same rate as those who had been diagnosed earlier on, as shown by the much sharper reduction in the relative frequency of medication use in the former subgroup. The rates of osteoporosis medication found in our study are substantially lower than those a recently published study found among female osteoporosis patients in Austria12. In that study, 350 patients of family physicians completed telephone surveys concerning their use of calcium and vitamin D supplements. In the telephone interview, 89% of the osteoporosis patients reported taking calcium and vitamin D supplements, although only 78% said they did so daily or most days. One reason for the remarkable difference compared to our study (where only 21% of women diagnosed with osteoporosis were taking medication of any kind at the time of interview) could be the significant differences in the health-care systems of European countries. For example, figures from Great Britain, where 32% of female osteoporosis patients surveyed reported taking calcium and vitamin D supplements12, accord very well with the rates found in our study population. Another reason for the difference could be the higher mean age (70) of our patients compared to the mean age (66) in the study by Resch et al.12. Older patients generally have more medications to take (polypharmacy), leading to reduced compliance with respect to taking of the calcium and vitamin D supplement. Another aspect to consider is that our study looked at hospitalized postmenopausal women, who may differ in some respects from outpatients.

Of interest is the increase in the prescription of bisphosphonates from 1.7% of subjects at admission to 6.3% at discharge (p < 0.001), a rate that did not change after discharge. There was a parallel increase from 8 to 11 % in bisphosphonate prescriptions among patients with known bone density loss. Bisphosphonates are currently considered the first-line preventive therapy for postmenopausal women with osteoporosis13. Bisphosphonate therapy is known to inhibit osteoclasts and thus bone resorption, resulting in an increase in bone density over the long term. Bisphosphonates are therefore considered particularly effective for 'high turnover' osteoporosis, of which postmenopausal osteoporosis is one example. It is also known, however, that reductions in fracture rates have so far been found only for limited periods. Thus the EPIC study found that in early postmenopausal women, daily taking of alendronate over 6 years resulted in a reduction in fracture rate from 11.5% in the control group (placebo) to 8.9% in the alendronate 5mg group11. The FLEX study showed that women with postmenopausal osteoporosis who had been on alendronate therapy for 5 years and then took a placebo for 5 years did not have a higher fracture risk - except for clinical vertebral fractures - than those who continued on alendronate for another 5 years14. For how long and at what dosage bisphosphonates should be taken thus remains unclear. This uncertainty, together with the markedly higher cost of bisphosphonates compared to that of calcium and vitamin D, could be a key reason for the relatively low rate of bisphosphonate prescription in Germany.

In contrast to the trend observed for bisphosphonates, use of estrogen sank from 5.1% (admission) to 2.5% (discharge) and to 0.5% 6-12 months after discharge (Table 6). Treatment with calcitonin or raloxifene was observed in only a tiny minority. With the exception of estrogen use prior to admission, significant age differences with regard to osteoporosis medication were not found at any point in the study.

Six to twelve months after hospital discharge, 4.3% of patients with distal radius fracture had suffered a subsequent fracture from minimal trauma. Two patients had sustained a refracture at the same location. The percentage of patients with subsequent fracture was lower among those receiving osteoporosis treatment (3.1%) than among non-treated individuals (4.5%), but these group differences were not large enough to be statistically significant (p - 0.79). The increase or decrease in fracture rates also reflects non-medication factors. One of these is physical activity. Because it is difficult to determine level of physical activity in patient interviews, difference in physical activity is a potential confounder of frequency of fractures after hospital discharge in our study as well.

Another noteworthy result of the interviews is that 6-12 months after discharge, 15% of subjects were still taking analgesics for pain in the distal radius area. The similarity to the results of a large study of patients with hip fracture15 is remarkable. In that study, more than 13% of the hip fracture patients reported still having pain in the hip area 6-12 months after discharge from hospital.

The marked undertreatment of at-risk patients with osteoporosis medication is consistent with reports from other studies. Freedman et al.16 performed a retrospective cohort study with 1162 women aged 55 years or older who sustained a distal radius fracture. Of these, only 2.8% (33) underwent a BMD measurement and only 23% (266) were treated with at least one of the medications approved for treatment of known osteoporosis. In contrast to the treatment data at discharge in our study, however, 20% of all patients were receiving hormone replacement therapy, compared with 2.5% in our study. This substantially larger percentage of patients taking hormone therapy is explained at least in part by the fact that the patients in the study by Freedman et al. were recruited roughly 10 years earlier. In the intervening 10 years, the attitude toward hormone therapy used only for postmenopausal osteoporosis treatment changed because of findings casting doubt on the risk-benefit ratio, especially with respect to invasive breast cancer (26% risk increase), coronary artery disease (20% risk increase), and stroke (41% risk increase)17. For the same reason the percentage of patients taking bisphosphonates in the Freedman study (3.4%) is only half the rate of our study (6.4%). The first major studies on alendronate therapy appeared only in 199618. Since such a large percentage of patients in the Freedman study had been receiving hormone therapy, it is not surprising that the rate of treatment declined significantly with increasing patient age. Because in Germany the main focus of osteoporosis treatment is on calcium and vitamin D intake as a preventive measure (along with other treatments such as regular exercise), a comparable decline in osteoporosis treatment with age was not found in our study.

Bone mineral density data were available in the records of roughly 30% of the patients in our study. Smith et al.19 found a very similar rate in their analysis of medical records of patients between ages 40 and 85 in Australia. Of the 218 subjects in that study who participated in a follow-up interview (78% female), 69 (32%) had undergone a BMD assessment, with 56% of the results indicating osteoporosis. The rate of only 15% of patients receiving osteoporosis medication (bisphosphonates being the most commonly prescribed) is also comparable to our findings in Germany, with the difference that in Germany dietary supplements are the more commonly prescribed treatment. However, the rate of postmenopausal women with a fragility fracture of the distal radius for whom BMD data are available can also be as low as 5%, as Cuddihy et al. found in a study from Olmsted County, Minnesota in the 1990s20.

In recent publications the percentage of patients who were prescribed osteoporosis medication at the time of discharge from hospital ranges from 15%21 and 16% 22, to 23%23 and around 26%24,25. In these studies, the percentage of patients who had previously undergone BMD testing differed considerably - if data were available at all - ranging from just over 10%21'2'1 to 24%25 and 34%22.

Our figures confirm both underassessment of bone density loss in at-risk patients, and undertreatment in patients who are diagnosed. In our view there continues to be a pressing need to educate both doctors and patients that a fragility fracture in a postmenopausal woman implies osteoporosis, until proven otherwise. The possible barriers to adequate diagnosis and treatment of osteoporosis in postmenopausal women with a distal radius fracture have already been discussed elsewhere26. We have already addressed the knowledge gap among physicians about the importance of a prior fracture as a risk factor for osteoporosis. As another possible barrier, we would like to point to the lack of consensus among physicians [e.g., orthopedic surgeons, internists, general practitioners) as to who is responsible for osteoporosis care, which is fostered in the German health system in particular by the open question of who bears the costs of diagnosis and treatment.

Some limitations of our study merit attention. First, we focused on hospitalized postmenopausal women and therefore our findings may differ to a certain extent from findings for other patient groups (outpatients, premenopausal women, men). second, we made the conservative assumption that estrogen therapy was prescribed for osteoporosis treatment. Thus, we may have somewhat overestimated rates of osteoporosis treatment. Third, we could not give precise data on the frequency of DEXA testing in hospital, since in most cases the records did not indicate how bone density was determined. It is believed that the actual rate of DEXA testing could be about 30%.

Conclusions We found that the vast majority of at-risk postmenopausal women with distal radius fracture from minimal trauma did not receive adequate assessment and treatment of osteoporosis. The potential to alter this pattern of practice represents a major public health opportunity.

Acknowledgments

This study was partially funded by an unrestricted educational grant from MSD Sharp & Dohme Germany. MSD Sharp & Dohme Germany did not influence study design, conduct of the study, data collection, management, analysis, interpretation of the data, manuscript preparation, or publication decisions.

List of abbreviations

ASA classification: American Society of Anesthesiologists physical status risk rating -

I: Healthy patient, no medical problems

II: Mild systemic disease

III: Severe systemic disease, but not incapacitating

IV: Severe systemic disease that is a constant threat to life

V: Moribund, not expected to live 24 hours irrespective of operation

BMD: Bone mineral density

DEXA: Dual energy X-ray absorptiometry

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CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-3562_3, Accepted for publication: 13 July 2007

Published Online: 3 August 2007

doi: 10.1185/030079907X219706

Heinz G. Endres(a), Burkhard Dasch(a), Christoph Maier(b), Margitta Lungenhausen(b), Rudiger Smektala(c), Hans J. Trampisch(a) and Ludger Pientka(d)

a Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Universitatsstrasse 150, Bochum, Germany

b Department of Pain Management, BG-Kliniken Bergmannsheil, Ruhr University Bochum, Buerkle de la Camp-Platz 1, Bochum, Germany

c Department of Surgery, Knappschaftskrankenhaus Bochum- Langendreer, Ruhr University Bochum, In der Schomau 23-25, Bochum, Germany

d Department of Geriatrics, Marienhospital Herne, Ruhr University Bochum, Widumer Sir. 8, 44627 Herne, Germany

Address for correspondence: Heinz G. Endres, Dr.med. Dipl.- Chem., Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Universitatsstr. 150, 44801 Bochum, Germany. Tel.: +49 234 32 26564; Fax: +49 234 32 06564; heinz.endres@ruhr- uni-bochum.de

Copyright Librapharm Sep 2007

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