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Skeletal Pain in Postmenopausal Women With Osteoporosis

January 10, 2007

By Scharla, S; Oertel, H; Helsberg, K; Kessler, F; Et al

Key words: Analgesia – Bone pain – Osteoporosis, postmenopausal – Raloxifene

ABSTRACT

Objective: To assess the prevalence of skeletal pain in postmenopausal women before the onset of raloxifene treatment and the further course of pain during treatment in a naturalistic setting.

Research design and methods: Prospective, uncontrolled, multicentre, 6-month, observational study in Germany. Clinical, diagnostic and pain data were collected at baseline, 6 weeks and 6 months of raloxifene treatment from 3299 female outpatients with postmenopausal osteoporosis. Physicians assessed the presence or absence of back pain, joint pain and diffuse bone pain at each visit, perceived sleep quality and the use of analgesics. Patients assessed intensity and frequency of pain using a 100mm visual analogue scale (VAS) and a 5-point scale (from ‘rarely’ to ‘permanently’), respectively.

Results: At baseline, patients had mean (SD) age 67.6 (9.3) years, 89.4% were reported to have reduced bone mineral density, 39.8% had pre-existing fractures and 93.4% had skeletal pain (physician assessment): 85.1% had back pain, 41.8% joint pain and 32.5% diffuse bone pain. Median pain intensity on VAS was 66.0 mm. After 6 months of raloxifene treatment the frequency and intensity of pain and use of analgesics for skeletal pain decreased consistently by approximately 50%. Pain frequency decreased in 58.2% and increased in 2.3% of patients. The median decrease in pain intensity from baseline to 6 months was 27.0 mm (46%). Patients’ subjective quality of sleep improved: the proportion of patients who were reported to sleep well increased from 21.3% at baseline to 46.7% at 6 months. The decrease in relative pain frequency was greatest with diffuse pain (67.6%) followed by joint pain (36.9%) and back pain (32.5%).

Conclusion: Raloxifene treatment in postmenopausal women with osteoporosis was associated with a marked reduction of skeletal pain and analgesic consumption and an improvement in subjective sleep quality. Further investigation in a randomised, placebo-controlled trial is warranted.

Introduction

Skeletal pain is a relatively common problem among women with postmenopausal osteoporosis and can be disabling, impairing patient functioning and quality of life1. The intensity and localisation of osteoporosis-associated skeletal pain varies among individuals, but back pain in the thoracic and lumbar spine region is the most common type of pain and is frequently associated with vertebral fracture.

A variety of underlying causes for osteoporosis-associated bone pain has been described. Back pain has been related to vertebral fractures2,3, vertebral deformities4,5, and increases in bone turnover markers6. Not all vertebral fractures are painful, but the pain seems to increase with the number and severity of vertebral fractures3. The acute pain associated with new vertebral fractures is often short-lived and resolves within a few weeks to months as the fracture stabilizes7. However, some osteoporosis patients may have persistent, chronic pain caused by further fractures or persistent vertebral deformity, leading to paraspinal muscle spasm and changes in spinal alignment8. In addition, it is currently assumed that high-turnover osteoporosis per se, such as that seen in the early postmenopause, can cause diffuse bone pain9. Further possible causes of chronic back pain, especially in older patients, include accompanying inflammatory and/or degenerative changes at the spinal column, such as spondylosis or osteoarthritis and concomitant rheumatic diseases10.

Little is known about the prevalence of these different types of pain in osteoporosis patients, and how the frequency and intensity of pain responds during treatment of osteoporosis.

Analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) or opioids, are commonly used to relieve osteoporosis- related pain, but frequently are associated with adverse effects. Various osteoporosis therapies have also been found to reduce osteoporosis-associated pain. Calcitonin, a polypeptide hormone that inhibits osteoclast-induced bone resorption, has been shown to be effective for treating bone pain, including the acute pain of osteoporosis-related vertebral fractures11,12. The mechanism of this analgesic effect remains unclear but evidence suggests that it may involve modulation of nociception in the central nervous system (CNS) via a direct receptor-mediated effect or an indirect endorphin- mediated effect7,13. The role of calcitonin in relieving chronic bone pain associated with osteoporosis is less clear. Several small, controlled, open-label studies have reported reduced chronic pain among osteoporosis patients receiving calcitonin7. However, a recent study showed that intranasal calcitonin for 3 months had no effect on chronic back pain intensity in postmenopausal women with osteoporosis14.

Back pain in patients with osteoporosis is reduced during long- term treatment with alendronate15 or teriparatide16-18. The mechanism of pain reduction with these drugs is unknown, but is thought to be related to the reduction in the number and severity of new vertebral fractures16. In contrast, data from the Study of Osteoporotic Fractures (SOF) showed that oestrogen replacement therapy in postmenopausal women was associated with an increased risk of back pain19.

Raloxifene is a selective oestrogen receptor modulator (SERM), indicated for the treatment and prevention of osteoporosis in postmenopausal women. Raloxifene 60mg/day reduces the risk of new moderate/severe vertebral fractures (which are associated with symptoms such as back pain) by 37% and 61% in postmenopausal women with and without pre-existing vertebral fractures, respectively20. In a previous prospective, observational study of the comorbidity of osteoporosis and cardiovascular diseases, there was a marked decrease of bone and joint pain during 6 months of raloxifene treatment, although pain data were collected as a secondary outcome measure and was not extensive21.

The aim of this prospective, uncontrolled, observational study was to assess the prevalence, intensity and possible underlying causes of skeletal pain, particularly back pain, in women with postmenopausal osteoporosis, and to assess the course of this osteoporosis-associated pain during 6 months of treatment with raloxifene in a naturalistic, observational setting.

Methods

Study design and patients

This was a prospective, uncontrolled, multicentre, observational study of postmenopausal women with osteoporosis, conducted by 810 office-based physicians in Germany. The study was conducted according to the local German laws and regulations. There were no specific requirements regarding the type and extent of patient information and consent to participate in an observational study, according to the regulations of the Federal German Drug Law.

The patients included in the study were postmenopausal women with osteoporosis whose physician intended to initiate treatment with raloxifene and who were willing to answer questions concerning pain; there were no formal inclusion or exclusion criteria. All treatment decisions and the dosage of raloxifene were at the discretion of the participating physician; no instructions were included in the study protocol.

Assessments

Data were collected by physicians at the baseline assessment (day of treatment initiation with raloxifene), and at approximately 6 weeks and 6 months of raloxifene treatment. The following data were recorded at the baseline visit: patient demographics; historical information on osteoporosis [presence of risk factors, decreased bone mineral density (BMD), vertebral and non-vertebral fractures without adequate trauma, history of falls and height loss]; presence of radiologically diagnosed degenerative changes of the spine; inflammatory and degenerative concomitant diseases of the skeletal system; medication for these concomitant diseases; and previous medication for the treatment of osteoporosis.

Bone pain

At each visit, patients indicated whether or not they had skeletal pain present and physicians specified the location of the skeletal pain as back pain, joint pain or diffuse bone pain. Patients with skeletal pain estimated the frequency and intensity of their pain during the previous 4 weeks. Pain frequency was rated on a 5-point Likert scale ranging from ‘rarely’ to ‘permanently’, and pain intensity was assessed using a 100mm visual analogue scale (VAS) ranging from 0mm = no pain to 100mm = very strong pain.

Use of analgesics

At each visit, the use of analgesics to treat skeletal pain was indicated by the participating physician on a 4-point Likert scale ranging from ‘less than once per month’ to ‘once daily or more’. The use of analgesics for non-skeletal pain (e.g. headaches, toothache) was also recorded.

Sleep quality

At each data collection point, the perceived quality of patient sleep was rated by the participating physician as ‘good’, ‘moderate’ or ‘poor’, based on statements made by the patient.

Biochemical markers of bone turnover

The availability of bone turnover data, the type of biochemical markers used for assessing bone formation and bone resorption and the status of the marker (increased, decreased, normal) were recorded at ea\ch data collection point.

The following data were also recorded at each data collection point: dosage of raloxifene; patient compliance with raloxifene (assessed by the physician as ‘daily intake’, ‘almost daily intake’ and ‘intake frequently missed’); concomitant osteoporosis medications prescribed; presence of non-skeletal pain; incidence and type of adverse events.

Analysis

All data are presented as descriptive summary statistics: i.e. means, standard deviations (SD), etc. for continuous variables, absolute and relative frequencies for categorical variables. For categorical variables of interest, 95% confidence interval limits (95% CL) were calculated. Changes from baseline to 6 weeks or 6 months were calculated for all patients with data available for the baseline visit and the respective postbaseline visit. To explore the effect of raloxifene on osteoporosis-associated pain in more detail, the relative change in pain intensity (%) (patient self-reported VAS scores) from baseline to 6 months was determined for subgroups of patients with the following characteristics: age (< 65 years vs. 65 years); body mass index (⓰¤ 25 vs. > 25); history of vertebral fragility fractures

; history of non-vertebral fragility fractures (yes or no); co-medication (previous or concomitant treatment with other anti-osteoporosis drugs, concurrent analgesic use); type of skeletal pain (back pain, joint pain, diffuse bone pain, or a combination of these); duration of pre-existing pain (<, 4 weeks, 4 weeks to 6 months, > 6 months); and potentially underlying cause(s) of skeletal pain [previous fragility fractures vs. degenerative or rheumatic/inflammatory disease vs. high bone turnover as determined by biochemical bone marker (s)]. All statistical analyses were performed using SAS version 8.2.

Results

Patient characteristics

A total of 3302 women with postmenopausal osteoporosis were included in the study and 3299 (99.9%) were eligible for analysis. Three patients were excluded from the analysis because no visit dates were available, raising the possibility that the data had been recorded retrospectively. Of the 3299 remaining patients, 79 (2.4%) failed to return for the second visit, and a further 129 patients (3.9%) failed to return for the final visit, such that data from all three visits were available for 3091 patients (93.7%) of the original cohort. A total of 252 patients (7.6%) discontinued raloxifene treatment before the end of the observation period, either because of an adverse event (n = 81), a physician’s recommendation (n = 51), the patient’s decision (n = 23), or other specified reasons (n = 90). In the remaining seven cases, the reasons for early discontinuation of treatment were not documented.

The baseline demographic and disease characteristics of the patients included in the analysis are summarised in Table 1. The majority of patients (89.4%) were reported to have reduced BMD. In total, 39.8% of patients had a history of one or several atraumatic fractures.

According to the physician assessment, 93.4% of all patients experienced skeletal pain at the start of raloxifene treatment (baseline visit). Similarly, 89.2% of patients reported having skeletal pain at baseline (VAS questionnaire). With respect to the type of skeletal pain (physician’s assessment), 85.1% of patients had back pain, 41.8% had joint pain and 32.5% had diffuse pain at baseline. Mean ( SD, median) pain intensity assessed by patients using the 100mm VAS scale was 62.7 ( 21.6, 66.0) mm at baseline. The median duration of pre-existing skeletal pain at baseline was 36 months, and 75% of patients had experienced skeletal pain for more than 10 months.

A high proportion of patients had concomitant diseases that may have contributed to their skeletal pain: 83.5% of patients had X- ray findings indicating degenerative changes in the spine region (e.g. spondylosis, osteophytes) and 21.7% of patients had known concomitant rheumatic/inflammatory degenerative disease (e.g. osteoarthritis).

Of the total patient cohort (N = 3299), only 525 (15.9%) patients had bone turnover data available at baseline; biochemical markers of bone formation and bone resorption were documented for 496 (15.0%) patients and 207 (6.3%) patients, respectively. Alkaline phosphatase (AP) was the bone formation marker measured most frequently (in 484 patients). All other markers of bone formation or resorption were measured in less than 2% of patients.

Table 1. Baseline demographic and disease characteristics of patients

At baseline, 58.1% of patients had received prior treatment for osteoporosis, with calcium/vitamin D supplementation being reported most frequently (45.0% of 3299 patients). Bisphosphonates had been used by 15.2% of patients, hormone replacement therapy by 8.7%, fluorides by 7.3% and calcitonin by 3.5% of patients.

Raloxifene was prescribed at the recommended dose of 60 g once daily for the majority of patients (99.5%, 3284/3299); 14 patients were prescribed raloxifene 120 g/day at least once and one patient was prescribed raloxifene 30 mg/day. Patient compliance with raloxifene treatment was rated high, with 83% of patients rated as ‘taking their raloxifene daily’. The majority of patients (80.2%, 2646/3299) started raloxifene treatment alone; concomitant osteoporosis medications such as bisphosphonates, calcitonin, fluorides were used in less than 3% of patients each. However, 37.6% of patients (1241/3299) received concomitant analgesics and/or anti- inflammatory drugs for the treatment of inflammatory degenerative disease such as osteoarthritis.

Changes in skeletal pain during treatment

The frequency of skeletal pain at baseline and during raloxifene treatment at Week 6 and Month 6 (patients’ assessment) is shown in Figure 1. The percentage of patients reporting permanent or frequent pain decreased from 78.1% at baseline to 34.9% after 6 months of raloxifene treatment. Overall, 58.2% of patients showed a decrease in their frequency of pain after 6 months of raloxifene treatment and 2.3% showed an increase in pain frequency.

Figure 2 shows the frequency of the different types of skeletal pain (physician assessed) at baseline and during raloxifene treatment for all eligible patients (N = 3299). For patients with data available at both baseline and Month 6 (n = 3057), there was a 32.6% relative decrease in the frequency of back pain (from 85.4% to 57.6%), a 36.9% relative decrease in the frequency of joint pain (from 41.4% to 26.1%) and a 67.6% relative decrease in diffuse bone pain (from 32.7% to 10.6%); the percentage of patients with no skeletal pain increased from 6.4% at baseline to 27.1% at 6 months.

Figure 1. Frequency of skeletal pain at baseline and during raloxifene treatment (patients’ assessment; N = 3299)

Figure 2. Frequency of pain at different skeletal sites at baseline and during raloxifene treatment (physicians’ assessment; N = 3299)

The intensity of skeletal pain (as assessed by patients wing the VAS) decreased during raloxifene treatment. The median percentage decrease in pain intensity from baseline to 6 months was 46% (mean 42%, 95% CL 40-44%; absolute median decrease 27.0mm) for the 2491 patients with data available at both time points. Pain reduction was similar regardless of age, BMI and anti-resorptive pre-treatment (data not shown). The pain intensity at baseline and after 6 months of raloxifene treatment in further selected subgroups of patients with different histories of osteoporosis and concomitant skeletal diseases as well as duration of pre-existing pain is summarised in Table 2. The median decrease in pain intensity did not differ relevantly between subgroups and was similar to that observed in the total group of patients with skeletal pain (46%); i.e. pain reduction occurred regardless of the duration or type of pre- existing pain or its underlying cause.

Of those 525 patients who had one or several biochemical markers of bone turnover documented at baseline, 185 women (35.5%) had at least one elevated marker, and in 93 patients (17.7%) all assessed biochemical markers were increased. At Month 6, 289 patients had documented bone marker data: 56 patients (19.4%) had at least one elevated biochemical marker of bone turnover. Among the subgroup of patients with skeletal pain and increased biochemical markers of bone turnover at baseline (n = 152), the median decrease in pain intensity after 6 months of treatment was 53% (mean 46%, 95% CL 40- 52%). However, only nine patients had both increased biochemical markers at baseline and no confounding factor for bone pain (i.e. vertebral fracture or concomitant degenerative, inflammatory or rheumatic disease). The median decrease in pain intensity (61%) after 6 months of treatment in this subgroup of patients was in the same range as in the other subgroups (Table 2), but the small sample size precludes firm conclusions from being drawn.

Table 2. Pain intensity at baseline (100mm VAS) and percentage reduction after 6 months of treatment with raloxifene in various subsets of the study population

Figure 3. Use of analgesics for skeletal pain at baseline and dunng raloxifene treatment (N = 3299)

Use of analgesics

The use of analgesics for skeletal pain decreased markedly during raloxifene treatment (Figure 3). At the start of raloxifene treatment (baseline), 56.4% of patients required analgesics at least once per week or more. The percentage of patients using analgesics at this rate had decreased to 27.6% at Month 6 of raloxifene treatment. By the end of 6 month of treatment with raloxifene, 37.8% of patients did not use analgesics for skeletal pain.

In addition, the percentage of patients using analgesics and/or antiphlogistics for concomitant inflammatory degenerative skeletal disease decreased from 37.6% at baseline to 27.0% at Month 6 of treatment.

To assess if changes in skel\etal pain and analgesic use may have been confounded by the presence of nonskeletal pain unrelated to osteoporosis, we determined the frequency of non-skeletal pain and the use of analgesics for this pain. Non-skeletal pain was present in 13.7% (453/3299) of patients at baseline and 64.2% of these patients (291/453) reported using analgesics for this pain. At 6 months, 290 patients (8.8%) had non-skeletal pain and 175 (60.3%) of these patients reported using analgesics.

Sleep quality

Patients’ perceived sleep quality (physician questioned) improved markedly during raloxifene treatment as shown in Figure 4. The proportion of patients with good sleep quality increased from 21.3% at baseline to 46.7% at Month 6 of raloxifene treatment. In addition, the percentage of patients with poor sleep quality decreased from 31.9% at baseline to 6.8% after 6 months of raloxifene treatment. Overall, 45.0% of patients reported an improvement in sleep quality, whereas only 2.7% of patients reported any worsening of sleep quality.

Tolerability

Adverse events were reported for 131 of 3299 patients (4.0%) and led to the discontinuation of raloxifene in 81 patients (2.5%). Most of the reported adverse events (168/186, 90.3%) were considered as related to raloxifene. The adverse events reported most frequently were hot flushes/hyperhidrosis (22 patients/7 patients, 0.7/0.2%), nausea (13, 0.4%), upper abdominal pain (7, 0.2%), stomach discomfort (7, 0.2%), peripheral oedema (7, 0.2%) and muscle cramps (7 patients each, 0.2%). The adverse events leading to discontinuation of raloxifene in at least two patients are listed in Table 3. Thirteen women experienced a serious adverse event, three of which were considered related to raloxifene: one patient experienced a retinal vein thrombosis with loss of vision in one eye approximately 4 months after starting raloxifene; one patient experienced a transient increase in hepatic enzyme levels approximately 1 week after starting raloxifene; and one patient with diabetes experienced increased blood glucose levels 1 day after starting raloxifene treatment. There were four deaths during the study, but none were related to raloxifene treatment.

Figure 4. Reported sleep quality at baseline and during raloxifene treatment (N = 3299)

Discussion

Skeletal pain, especially back pain, is common in postmenopausal women with osteoporosis. Individualised pain management is important to prevent further progression of bone loss due to immobilisation. In this prospective, uncontrolled, observational study of postmenopausal women with osteoporosis, the majority (89% by patients’ self-assessment, 93% by physicians’ assessment) had skeletal pain before starting raloxifene treatment. The pain had been present for more than 10 months in 75% of patients, and back pain was the most common type of pain, being present in 85% of patients. There was a marked reduction in the frequency of skeletal pain during treatment with raloxifene for 6 months; the reduction in pain was seen for all types of skeletal pain, but the greatest relative decrease was seen for diffuse bone pain (68%). In addition, the intensity of skeletal pain decreased by approximately 50% over the 6-month treatment period. This reduction in pain was accompanied by decreased use of analgesics by approximately 50% and improved subjective patient quality of sleep.

Table 3. Adverse events leading to discontinuation of raloxifene treatment in at least two patients (n = 3299)

Vertebral fractures are regarded as a major cause of back pain. However, back pain is common among older adults and may have many causes that are not directly related to vertebral fracture. The prevalence of back pain in the present study (85%) was much higher than the prevalence of radiologically confirmed pre-existing vertebral fractures (new, 11%; old, 23%). Our findings are consistent with those of a cross-sectional study of older women (aged 65-75 years) with osteoporosis, which reported a high prevalence of back pain (75%), although only 13% of women had previously diagnosed vertebral fractures22. Likewise, in the Study of Osteoporotic Fractures, only about 10% of postmenopausal women had vertebral deformities that caused chronic pain4. Thus, fracture- associated pain is only one major cause of back pain and much of the back pain experienced by the postmenopausal women in the present study must be due to other causes. Correspondingly, a high proportion of patients had relevant concomitant diseases that may have contributed to the presence of back and/or skeletal pain: 83% of patients had X-ray findings indicating degenerative changes at the spine and 22% had concomitant inflammatory degenerative changes, such as osteoarthritis.

Our findings of pain reduction with raloxifene are in agreement with a previous observational study in women with osteoporosis, which found that the frequency of severe bone and joint pain was reduced from 46% to 3% after 6 months of treatment with raloxifene21. Moreover, the magnitude of pain reduction in the present study was similar to that seen when the analgesic drug flupirtine was used to treat chronic pain in patients with osteoporosis23. In a recent randomised placebo-controlled study of postmenopausal women with osteoporosis and chronic back pain, there was a trend towards reduction in pain intensity with raloxifene treatment at both 6 and 12 months which was not seen in the control group; however, the differences between the two groups did not reach statistical significance24. The reasons for this lack of significant pain reduction with raloxifene in the Papadokostakis study compared with ours are unclear. Possible explanations may include the differences in study design, statistical analysis methods (within- group vs. between-group comparison), and – most importantly – the greater baseline mean pain intensity (VAS scores) in our study cohort (63 mm) compared with the Papadokostakis study cohort (39 mm), allowing for a more pronounced treatment effect.

Interestingly, we found that the greatest decrease in pain was seen for diffuse bone pain, which was reduced by about 68% after 6 months of raloxifene treatment. Diffuse bone pain in patients with osteoporosis is thought to be caused by high bone turnover9. This implies that the pain alleviating effect of raloxifene might be associated with a reduction in bone turnover. Indeed, raloxifene has been shown to reduce bone turnover in younger and older postmenopausal women with high-turnover osteoporosis and in elderly women living in long-term care facilities25,26. Moreover, marked reductions in biochemical markers of bone turnover have been seen after 6 months of treatment with raloxifene in postmenopausal women27. We were unable to examine the effects of raloxifene on bone turnover thoroughly in the present study because only a relatively small number of patients had bone turnover data available at baseline and 6 months. However, even in this limited subset of our cohort, we observed a clear decrease in the proportion of patients with bone marker elevations from baseline (35.5%) to Month 6 (19.4%).

Although bone pain is common in osteoporosis, its pathophysiology is not completely understood. Nociceptors in bone tissue respond to various stimuli (mechanical, thermal, chemical). Injury or inflammation results in the release of a variety of chemical mediators (e.g. prostaglandins, cytokines, growth factors) which not only stimulate osteoclast activity, but also activate nociceptors and decrease their threshold for activation28,29.

The mechanism of action of raloxifene in reducing pain in postmenopausal women with osteoporosis is unknown. Agents used to treat bone pain, such as calcitonin, have direct effects on osteoclasts, decrease bone turnover, may exert an anti-inflammatory effect and may reduce pain by secondary effects to diminish nociceptor activation28. It is, therefore, conceivable that, conversely, anti-resorptive drugs such as raloxifene may reduce bone pain by suppressing osteoclast activity and thus the secretion of cytokines from osteoclasts. Some of the pain reduction is related to the effect of raloxifene on fracture reduction, as recently published data from the MORE trial shows that the risk of new vertebral fractures was reduced after 3-6 months of raloxifene treatment30. However, raloxifene also has oestrogen-like effects in bone tissue and may influence nociceptive processing in the CNS24.

Analgesic use decreased during raloxifene treatment and was paralleled by improvement of perceived sleep quality. The proportion of patients requiring analgesics for skeletal pain at least once per week was reduced by about 50% from 56% at baseline to 28% after 6 months of raloxifene treatment. Previous studies of the analgesic effect of calcitonin have shown that pain relief ; was accompanied by reduced analgesic consumption7.

Sleep disturbances are common among people with acute and chronic pain. In the present study, 78% of patients reported impaired (moderate or poor) quality of sleep at baseline, but this figure had fallen to 46% after 6 months of raloxifene treatment. Previous studies have not specifically examined the effects of treatment on sleep in postmenopausal women with osteoporosisassociated pain.

Our study has several important strengths. It was a large, longitudinal study of postmenopausal women with osteoporosis in actual clinical practice, with similar characteristics to those patients who took part in the large, randomised MORE study31. Our study evaluated changes in pain over time and has advantages over cross-sectional studies, which may not capture transient increases or decreases in pain. Pain was the primary outcome measure in our study and both the frequency and intensity of pain were assessed. Furthermore, we assessed the prevalence of all types of skeletal pain. In contrast, previous studies have tended to focus on back pain in women w\ith or without prevalent vertebral fractures.

Our study also has several limitations. Firstly, due to the uncontrolled nature of the study and lack of a control (placebo- treated) group, a cause-effect relationship between raloxifene and pain reduction cannot be proven and bias cannot be ruled out. As this was an observational study in a naturalistic setting that included a large number of participating sites, source data verification was limited. In consequence, the high standards of data validation that are usually applied to RCTs could not be applied to this study. Whenever information was not provided by a physician, this had to be accepted and there was no way to obtain this information. Furthermore, statistical methods commonly applied in RCTs to compensate for missing values (such as intention-to-treat analysis using the Last Observation Carried Forward approach) were not employed. These limitations are partly mitigated, however, by the large sample size and by the relatively high internal consistency of the data (for example, good agreement between physician assessments and patients’ self-assessments).

Conclusions

In this observational study of postmenopausal women with osteoporosis, we have shown that the frequency and intensity of skeletal pain was reduced during 6 months of raloxifene treatment. All types of skeletal pain, including back pain, were reduced and this was accompanied by a reduction in the use of analgesics and improved sleep quality. The reduction of osteoporosis-related skeletal pain with raloxifene warrants further investigation in a randomised, placebo-controlled trial.

Acknowledgements

This study was sponsored by Lilly Deutschland GmbH.

The authors thank all the patients who volunteered to give information for this study and Elke Gruening, Medical Department, Lilly Deutschland, for help with the conduct of the study. Deirdre Elmhirst, PhD, assisted in the editorial development of this manuscript.

Material contained in this paper was presented in two posters at the 27th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR), September 23-27, 2005, Nashville, Tennessee, and in one poster at the Annual Meeting of the European League Against Rheumatism (EULAR), 8-11 June 2005, Vienna, Austria. The references for the corresponding abstracts are listed as Refs 32, 33 and 34 respectively.

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

Paper CMRO-3569_2, Accepted for publication: 05 October 2006

Published Online: 30 October 2006

doi: 10.1185/030079906X154097

S. Scharla(a), H. Oertel(b), K. Helsberg(b), F. Kessler(b), F. Langer(b) and T. Nickelsen(b)

a Practice for Internal Medicine and Endocrinology, Bad Reichenhall, Germany

b Medical Department, Lilly Deutschland GmbH, Bad Homburg, Germany

Address for correspondence: Thomas Nickelsen MD, PhD, Professor of Internal Medicine, Department Head, Endocrine Research, Lilly Deutschland GmbH, Saalburgstrasse 153, D-61350 Bad Homburg, Germany. Tel.: +49 6172 273 2595; Fax: +49 6172 273 2427; email: nickelsen_thomas_n@lilly.com

Copyright Librapharm Dec 2006

(c) 2006 Current Medical Research and Opinion. Provided by ProQuest Information and Learning. All rights Reserved.




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