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Background: Denosumab is a fully human IgG2 monoclonal antibody that, neutralizing the receptor activator of nuclear factor kappa-Β ligand (RANKL), inhibits the osteoclast-mediated bone resorption. It is yet to be defined if denosumab can reduce osteoporosis-related disability and improve health-related quality-of-life (HRQoL) in patients with fragility fractures. Objective: To assess the effectiveness of denosumab in reducing back pain related disability and improving HRQoL in osteoporotic post-menopausal women with vertebral fractures. Research design and methods: A real practice prospective study was carried out, enrolling women over 50 years with a post-menopausal osteoporosis that experienced at least one vertebral fracture receiving subcutaneous denosumab (60 mg, every 6 months), calcium carbonate (500-1000 mg/day) and cholecalciferol (800 IU/day) for 1 year. Back pain related disability was assessed as the primary outcome using the Spine Pain Index (SPI); secondary outcomes were: SF-12 (Physical Health Composite Score, PCS, and Mental Health Composite Score, MCS), and EuroQol-5D (EuroQol-5D-3L index and EuroQol-Visual Analog Scale, EQ-VAS). All outcome measures were assessed at baseline (T0), after 6 months (T1), and after 12 months (T2) of treatment. Trabecular Bone Score (TBS), lumbar spine (LS) and femoral neck (FN) BMD at T0 and T2 were also evaluated. Results: This study included 140 post-menopausal women, mean age = 70.60 (SD = 8.81) years. There were statistically significant differences after 12 months (T2-T0) in all outcomes assessed: SPI ( p  < 0.001), SF-12 PCS ( p  < 0.001), SF-12 MCS ( p  < 0.001), EQ-5D-3L index ( p  = 0.039), and EQ-VAS ( p  = 0.003). Moreover, there was a significant improvement of both LS BMD ( p  < 0.001) and FN BMD ( p  < 0.001). No local or systemic adverse events, including new vertebral fractures, osteonecrosis of the jaw and atypical femur fractures, were reported. Conclusions: The data demonstrated that denosumab was effective in reducing back pain related disability and in improving HRQoL in post-menopausal women with vertebral fractures.

Background: Establishing content validity is an essential component of instrument development., Objective: To assess the content validity and patient interpretation of the Self-Reported Misuse, Abuse and Diversion of Prescription Opioids (SR-MAD) instrument., Methods: A cross-sectional, qualitative study was conducted in patients with chronic or acute pain. Patients were recruited from three patient groups (opioid naïve, known opioid abusers, and chronic opioid non-abusers). After patients completed the SR-MAD, they participated in an in-person cognitive interview to assess the patient's understanding of the instrument. Descriptive statistics and content analysis were performed., Results: Fifty-seven patients (Wave 1: 20; Wave 2: 37) were enrolled and completed the SR-MAD and cognitive interview. Mean age was 54.5 ± 13.7 years (range 25-84) with 12.5 years of living with pain. The most common chronic pain conditions were back pain (68%), neck pain (32%), and osteoarthritis (25%). Overall, most patients understood the meaning of each question and were able to describe each item using their own words. Many patients reported that some questions were not applicable to them but understood the meaning of the questions as well as the need to ask questions about misuse, abuse, and diversion of opioid medications. Minor revisions to the SR-MAD wording, response options, recall period, and the definition of "opioid", were recommended by the patients in both waves., Limitations: Given its qualitative design, this study has a small sample size. Additionally, quantitative validation of the SR-MAD is needed., Conclusion: The SR-MAD, developed based on expert consensus and revised with patient input, is a 15-item self-report instrument that can be used to identify and monitor prescription opioid abuse, misuse, and diversion.

Objective: To observe and compare back pain and health-related quality of life (HRQoL) in postmenopausal women with a prior unsatisfactory response to antiresorptive therapy, treated with teriparatide (TPTD) or alternative treatments in normal clinical practice., Research Design and Methods: Prospective, observational, multicentre, 24-month study of postmenopausal women with osteoporosis. A back pain and HRQoL questionnaire (European Quality of Life Questionnaire, EQ-5D) including visual analogue scale (VAS) was completed at each visit., Results: A total of 153 patients were enrolled, 105 patients started TPTD treatment during the study (TPTD cohort) and 48 patients did not take TPTD treatment at any time during the study (non-TPTD cohort). Four patients did not meet the inclusion criteria for the study. Of the patients in the non-TPTD cohort, 31 (68.9%) took antiresorptives during the study. The patients selected by the investigator for teriparatide treatment were distinctly different from those not selected. At baseline, the mean back pain VAS was greater in the TPTD than the non-TPTD cohort, 64  mm and 42 mm, respectively (p < 0.001). During the study, compared with baseline, the mean back pain VAS decreased in the TPTD cohort at all visits (p < 0.001). In the non-TPTD cohort, a transitory decrease in the mean after 12 months was observed (-10 mm, p = 0.023) only. After 24 months, the mean back pain VAS improved in the TPTD cohort (-36 mm, p < 0.001) while no change was observed in the non-TPTD cohort (-4 mm, p = 0.467). At baseline, the mean EQ-VAS was lower in the TPTD than in the non-TPTD cohort, 40.8 and 55.2, respectively (p < 0.001). After 24 months, EQ-VAS improved in both cohorts (TPTD 34, p < 0.001 and non-TPTD 9, p = 0.026)., Conclusions: TPTD-treated patients had more back pain and lower HRQoL at baseline. In the TPTD cohort the mean value was consistently and significantly improved in back pain and quality of life. In the non-TPTD cohort, the mean improvement in back pain and QoL was inconsistent possibly due to the initially higher QoL and lower back pain leaving less room for improvement. These results should be interpreted in the context of limitations related to a non-randomised observational study.

Objective: To investigate changes in back pain in postmenopausal women with severe osteoporosis who received teriparatide for 24 months or switched at 12 months to raloxifene or no active treatment., Study Design and Methods: This prospective, controlled, randomised, open-label, 2-year study enrolled 868 postmenopausal women with osteoporosis and a recent fragility fracture. After 12 months of teriparatide (20 microg/day), 507 patients were randomised to further teriparatide (n = 305), raloxifene 60 mg/day (n = 100), or no active treatment (n = 102) for another 12 months (substudy 1); in substudy 2, 199 patients continued teriparatide. All received calcium and vitamin D supplementation. Back pain was self-assessed by patients using a visual analogue scale (0-100 mm). Changes in back pain were analysed using a mixed model for repeated measures., Results: During year 1, back pain decreased from a mean (SD) of 48.9 mm (24.0) at baseline by 11.5 mm (p < 0.001) in the total study population. In substudy 1, mean change in back pain from month 12 (randomisation) to 24 months was -2.2, -4.4 and +0.7 mm in the teriparatide (p = 0.076), raloxifene (p = 0.041), and no active treatment groups (p = 0.751). There were no between-group differences from randomization to 18 or 24 months. In a sensitivity analysis excluding patients with low baseline back pain (VAS < 30 mm), mean change from randomisation to endpoint was significant for teriparatide (-3.9 mm, p = 0.006) and raloxifene (-6.3 mm, p = 0.018) groups. Subgroup analyses of 503 patients who received teriparatide for up to 2 years showed that patients with a recent vertebral fracture had a greater decrease in back pain than those without (p < 0.05). Those with and without mild back pain (>or=30 mm), and those with and without severe back pain (>or=60 mm) at baseline all had a statistically significant reduction in back pain after 24 months (p < 0.05)., Conclusions: Teriparatide treatment is associated with significant reductions in back pain regardless of the presence of recent vertebral fracture. These results need to be considered with caution due to the open-label design of the study.

Objective: To review the efficacy and safety of current treatments for acute low back pain., Research Design and Methods: PubMed was searched for clinical trials in which the words, acute, back, and pain all appeared in the study summary. The search was from the earliest references included in this database (1949) until 1 May 2009. This resulted in retrieval of 129 papers. Review of study summaries indicated that 36 provided information about either a topical treatment or oral therapy for acute low back pain. In addition, studies included as part of the evidence base for the Evidence Review of American Pain Society/American Academy of Pain Medicine Evidence Review for Evaluation and Management of Low Back Pain were reviewed., Results: Recommended topical and systemic pharmacologic treatments for acute low back pain include application of superficial heat, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), skeletal muscle relaxants/benzodiazepines, and opioids including tramadol. Only a small number of studies compared different approaches to treatment of acute back pain and most failed to demonstrate significant differences among treatments. Available results support the view that both NSAIDs and low-level continuous heat treatment are more effective than acetaminophen and that heat treatment is also significantly more effective than ibuprofen. A potential limitation of this study is that information from trials published in journals not included in PubMed or reported only at meetings and not yet published was not included., Conclusions: A wide range of treatments is currently recommended for the management of patients with acute back pain and all are supported by results from controlled clinical trials.

Background: Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain., Methods: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients >or= 75 years) or 300-400 mg once daily (patients < 75 years)., Results: A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator., Conclusions: Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.

Objective: This prospective, randomized, open-label, multicenter, community-based study was conducted to compare cyclobenzaprine 5 mg three times daily (TID) orally (CYC5) given for 7 days as monotherapy or in combination with ibuprofen 400 mg TID (CYC5/IBU400) or 800 mg TID (CYC5/IBU800) in adults with acute neck or back pain with muscle spasm., Study Design: Eligible patients were 18-65 years old, had cervical or thoracolumbar pain and spasm for < or = 14 days, and, aside from the prescribed study medications, discontinued treatment with all analgesics, anti-inflammatory agents, and skeletal muscle relaxants during the study period. Randomization was 1:1:1 to the three treatment groups. Treatment outcome was assessed after 3 and 7 days of therapy using five patient-rated scales: spasm, pain, patient global impression of change (PGIC), medication helpfulness, and Oswestry Disability Index (ODI)., Results: A total of 867 patients provided postbaseline data and were included in the intent-to-treat population (CYC5, n = 288; CYC5/IBU400, n = 286; CYC5/IBU800, n = 293). All three treatment groups demonstrated significant improvements from baseline in PGIC, spasm, pain, ODI, and medication helpfulness (p < 0.001 for all comparisons) after 3 and 7 days of therapy. There were no significant differences in mean PGIC among groups after 3 days of therapy (p = 0.65 for treatment effect) or after 7 days of therapy (primary endpoint; p = 0.41). A PGIC responder analysis of changes from baseline showed that 88% and 93% of patients reported at least mild improvement after 3 and 7 days of therapy, respectively. All three treatments were well tolerated, with no significant differences between treatments regarding the number of adverse events (AEs) reported or number of patients reporting AEs. The most common AEs in all groups were fatigue, somnolence, dizziness, sedation, and nausea. Limitations of this study include an unblinded design and possible introduction of bias into efficacy and safety results by use of a voluntary telephone reporting system., Conclusions: This randomized, community-based clinical trial demonstrated that combination therapy with cyclobenzaprine 5 mg TID plus ibuprofen was not superior to cyclobenzaprine 5 mg TID alone in adult patients with acute neck and back pain with muscle spasm. All treatments were well tolerated.

Objective: Documentation of the clinical results obtained utilizing perispinal etanercept off-label for treatment-refractory back and neck pain in a clinical practice setting., Research Design and Methods: The medical charts of all patients who were treated with etanercept for back or neck pain at a single private medical clinic in 2003 were reviewed retrospectively. Patients were treated if they had disc-related pain which was chronic, treatment-refractory, present every day for at least 8 h, and of moderate or severe intensity. Patients with active infection, demyelinating disease, uncontrolled diabetes, lymphoma or immunosuppression were excluded from treatment with etanercept. Etanercept 25 mg was administered by subcutaneous injection directly overlying the spine. Visual Analogue Scales (VAS, 0-10 cm) for intensity of pain, sensory disturbance, and weakness prior to and 20 min, 1 day, 1 week, 2 weeks, and 1 month after treatment were completed. Inclusion criteria for analysis required baseline and treatment VAS data., Main Outcome Measures: Before and after treatment VAS comparisons for intensity of pain, sensory disturbance, and weakness., Results: 143 charts out of 204 met the inclusion VAS criteria. The 143 patients had a mean age of 55.8 +/- 14, duration of pain of 9.8 +/- 11 years, and an initial Oswestry Disability Index of 42.8 +/- 18, with 83% having back pain, 61% sciatica, and 33% neck pain. 30% had previous spinal surgery, and 69% had previously received epidural steroid injections (mean 3.0 +/- 3). The patients received a mean of 2.3 +/- 0.7 doses of perispinal etanercept separated by a mean interval of 13.6 +/- 16.3 days. The mean VAS intensity of pain, sensory disturbance, and weakness were significantly reduced after perispinal etanercept at 20 min, 1 day, 1 week, 2 weeks, and 1 month with a p < 0.0001 at each time interval for the first dose in this patient population., Conclusions: Perispinal etanercept is a new treatment modality which can lead to significant clinical improvement in selected patients with chronic, treatment-refractory disc-related pain. Generalizability of the present study results is limited by the open-label, uncontrolled methodology employed. Based on this and other accumulating recent studies, etanercept may be useful for both acute and chronic disc-related pain. Further study of this new treatment modality utilizing double-blind placebo controlled methodology is indicated. NOTE: This treatment method is protected by multiple patents awarded to Edward Tobinick MD, including U. S. patents 6 015 557; 6 177 077; 6 419 944; 6 537 549 and Australian patent 758 523.

An open, multi-centre study was carried out in patients with various moderate to severe painful conditions to assess the effectiveness of zomepirac in relieving pain. Patients were treated with 300 mg to 600 mg zomepirac daily for 7 days. Data from 15,484 patients have been analyzed. Most of the patients (75%) were already being treated with an analgesic on entry and more than half of them had been prescribed this by their doctor. Almost half, however, had still been in pain for more than 4 weeks before receiving zomepirac. An analysis of pain severity assessments showed a reduction from an initial score of 2.4 to 1.3 (on a 4-point rating scale). Global responses were recorded and 71.7% of the patients were considered to have improved according to the opinion of both doctors and patients, with the best response (84.1%) being observed in those with acute painful states such as sprains, strains and fractures and with pain of short duration. Pain frequently disrupts sleep, and 46.2% of patients reported their sleep as 'bad' or 'very bad' on entry to the study. After treatment, this figure was reduced to 15.1%. The side-effects reported, which were mainly gastro-intestinal, were mild in general and led to withdrawal of only 7.2% of the patients before completion of treatment.

Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200 mg meptazinol or 250 mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal.

A double-blind trial of azapropazone (300 mg. 4-times daily) and ketoprofen (50 mg. 4-times daily) was carried out in 50 patients with acute backache sufficiently severe to necessitate hospital admission. Of 39 patients who completed the full 3-weeks' study period, 18 preferred azapropazone therapy, 10 preferred ketoprofen, and 11 showed either preference for the intermediate placebo period or no preference at all. Ten patients suffered from sufficiently severe side-effects with ketoprofen to necessitate their withdrawal from the trial. There were no similar episodes of withdrawal occurring during the azapropazone period.

The marketed formulations of 6 analgesic preparations were compared in the treatment of patients suffering from acute exacerbations of low back pain using a crossover trial of balanced incomplete block design. Sixty out-patients with symptoms resulting from a mechanical or degenerative condition were each prescribed 3 drugs which were administered consecutively for 1 week each. The medications (and daily dosages) were coded as A --aspirin (3600 mg), B --dextropropoxyphene plus paracetamol (260 mg plus 2600 mg), C --indomethacin (150 mg), D --mefenamic acid (1500 mg), E --paracetamol (4000 mg), and F --phenylbutazone (300 mg). Daily pain scores were significantly lower (p less than 0.05) during treatment D than during treatments E and B, and significantly lower (p less than 0.05) during treatment A than during treatment B. There were large and significant differences between treatments in the percentages of recommended doses acceptable to the patients and in the number of defaults from the prescribed regimens. The patients chose F and D significantly more (p less than 0.05) often than A. Overall, there were consistently superior performances by mefenamic acid and phenylbutazone with little to choose between the two.