The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice. Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry. Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone. Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL. Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups. Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects of hormone treatments upon murine-derived bone cells will be investigated to provide mechanistic insights

Abstract. Objective. In this phase 2 clinical trial (EudraCT 2011-000541-20) we examined the effect of denosumab versus placebo on osteolytic lesion activity in patients undergoing revision surgery after THA. Methods. Men and women ≥ 30 years old scheduled for revision surgery for symptomatic, radiologically-confirmed osteolysis were randomised (1:1) to receive either denosumab 60mg or placebo subcutaneously eight weeks prior to operation. At surgery, biopsies from the osteolytic membrane-bone interface were taken for histomorphometric analysis of osteoclast number, the primary outcome measure. Secondary outcome measures included other static histomorphometric indices and systemic bone turnover markers. Adverse events and patient-reported clinical outcome scores were recorded as safety endpoints. Results. Of the 24 subjects enrolled, 22 completed the study (10 denosumab) and comprise the per-protocol analysis. There were no differences in baseline characteristics and bone turnover markers between groups (p>0.05). The denosumab group had 78% fewer osteoclasts at osteolytic lesion sites (95% CI −61 to −95, P=0.011), 81% lower osteoclast surface (−70 to −95, P=0.009), and 73% lower eroded surface (−54 to −92, P=0.020) compared to the placebo group. Number of osteoblasts and osteoblast surface were also reduced by 81% (−62 to −100, p=0.021) and 82% (−64 to −101, p=0.017), respectively. Immunocytochemistry for cell proliferation (Ki67) and apoptosis (Caspase 3) identified no differences between the groups (p>0.05). At surgery, serum CTX-I in the denosumab group was 80% lower (−65 to −95, p<0.001), TRAP5b −65% (−40 to −90, p<0.001), PINP −53% (−41 to −65, p<0.001). Patient-reported outcome measures and the rate of adverse events (denosumab 6, placebo 7) were similar between groups (P>0.05). Conclusion. A single dose of denosumab reduced osteoclast activity within osteolytic lesions and was safe to administer. These data provide a biological basis for a phase 3 trial using clinical outcomes of pain, function and prosthesis survival as the study endpoints. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Introduction and Objective. Global prevalence of obesity has risen almost three-fold between 1975 and 2016. Alongside the more well-known health implications of obesity such as cardiovascular disease, cancer and type II diabetes, is the effect of male obesity on testosterone depletion and hypogonadism. Hypogonadism is a well-known contributor to the acceleration of bone loss during aging, and obesity is the single biggest risk factor for testosterone deficiency in men. Understanding the micro and macro structural changes to bone in response to testosterone depletion in combination with a high fat ‘Western’ diet, will advance our understanding of the relationship between obesity and bone metabolism. This study investigated the impact of surgically induced testosterone depletion and subsequent testosterone treatment upon bone remodelling in mice fed a high fat diet. Materials and Methods. Male ApoE. −/−. mice were split into 3 groups at 7 weeks of age and fed a high fat diet: Sham surgery with placebo treatment, orchiectomy surgery with placebo treatment, and orchiectomy surgery with testosterone treatment. Surgeries were performed at 8 weeks of age, followed by fortnightly testosterone treatment via injection. Mice were sacrificed at 25 weeks of age. Tibiae were collected and scanned ex-vivo at 4.3μm on a SkyScan 1272 Micro-CT scanner (Bruker). Left tibiae were used for assessment of trabecular and cortical Volumes of Interest (VOIs) 0.2mm and 1.0mm respectively from the growth-plate bridge break. Tibiae were subsequently paraffin embedded and sectioned at 4μm prior to immunohistochemical evaluation of alkaline phosphatase. Results. Trabecular bone volume and mineral density were significantly reduced in orchiectomised mice compared to sham-operated controls; and these parameters were normalised to control levels in orchiectomised mice treated with testosterone. In contrast, Trabecular thickness was significantly higher in testosterone depleted animals. Cortical bone parameters and body weights did not significantly differ between groups. Levels of alkaline phosphatase did not differ significantly in cortical or trabecular osteoblasts between groups. Conclusions. Findings suggest that testosterone deficiency significantly reduces trabecular bone parameters, and testosterone therapy may be a useful intervention for the loss of bone mass in testosterone deficient males. These results indicate that testosterone therapy may be useful for the treatment of trabecular bone frailty in testosterone deficient males. Observed changes in trabecular bone do not appear to be due to decreased mineralisation caused by osteoblast alkaline phosphatase. Ongoing work includes histology analysis to elucidate the mechanisms underpinning the changes seen in the bones of testosterone deficient animals

The multimodal management of canal stenosis is increasing, and inhibitors of central sensitization are playing a crucial role in central sensitization processes. Pregabalin and gabapentin are antiepileptic drugs that reduce presynaptic excitability. The objective of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of canal stenosis. A literature search was conducted in four databases. The inclusion criteria were studies that compared pregabalin or gabapentin with a control group in lumbar canal stenosis. Randomized clinical trials and a comparative retrospective cohort study were included. The main clinical endpoints were VAS/NRS, ODI, and RDQ (Roland Morris Disability Questionnaire) at 2, 4, 8 weeks, and 3 months, adverse events, and walking distance were also collected. Data were combined using Review Manager 5.4 software. Six studies and 392 patients were included. The mean age was 60.25. No significant differences were observed in VAS at 2, 4, and 8 weeks: (MD: 0.23; 95% CI: −0.63-1.09), (MD: −0.04; 95% CI: −0.64 to −0.57), and (MD: −0.6; 95% CI: −1.22 to 0.02). Significant differences were observed in favor of pregabalin with respect to VAS at three months: (MD: −2.97; 95% CI: −3.43 to −2.51). No significant differences were observed in ODI (MD: −3.47; 95% CI: −7.15 to −0.21). Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95%CI 1.28-27.05). Walking distance and RDQ could not be compared, although the results were controversial. Gabapentinoids have not been shown to be superior to other drugs used in the treatment of LSS or to placebo. However, they have shown a higher incidence of adverse effects, improved results in VAS at 3 months, and a slight improvement in ambulation at 4 months in combination with NSAIDs compared to NSAIDs in monotherapy

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Introduction and Objective. Tranexamic acid (TXA) is used across surgical specialties to reduce perioperative bleeding. It has been shown to be effective in trauma, spinal surgery, and lower limb arthroplasty. The aim of this study is to investigate the clinical effectiveness of TXA in all types of shoulder surgery on bleeding and non-bleeding related outcomes. Materials and Methods. This study was registered prospectively on the PROSPERO database (ref: CRD42020185482). A systematic review and meta-analysis of randomised controlled trials (RCTs) investigating intra-operative use of TXA versus placebo in any type of surgery to the shoulder girdle. Electronic databases searched included MEDLINE, EMBASE, PsychINFO, and the Cochrane Library. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and Jadad score. Certainty of findings were reported using the GRADE approach. The primary outcome was total blood loss. Secondary outcomes included patient reported outcome measures, adverse events, and rate of blood transfusion. Results. Eight RCTs were included in the systematic review and data from 7 of these studies pooled in the meta-analysis. A total of 708 patients were randomized across the studies (406 received TXA, 302 received placebo). Studies included patients undergoing anatomic or reverse total shoulder arthroplasty, open Latarjet surgery, and arthroscopic rotator cuff repair. Pooled analysis demonstrated significant reduction in perioperative bleeding with TXA compared to controls; estimated total blood loss (mean difference [MD], −209.66; 95% CI −389.11 to −30.21; p=0.02), and post-operative blood loss (via drain output) (MD, −84.8ml; 95% CI, −140.04 to −29.56; p=0.003). A mean difference in Visual Analogue Scale (VAS) of 2.93 was noted in favour of TXA (95% CI 0.2 to 5.66; p=0.04). Conclusions. Whilst noting some risk of bias within the studies, TXA was effective in reducing blood loss and pain in shoulder surgery. There may be a benefit of TXA use in both open and arthroscopic shoulder procedures. Larger, low risk of bias, RCTs for specific surgical shoulder procedures are required

Matrix therapy is a newly coined name emphasizing the importance of the extracellular matrix in regenerative medicine. Heparan sulfates (HS) are key elements of the extracellular matrix (ECM) scaffold which store and protect most growth factors/cytokines controlling the cell migration and differentiation required for healing processes. We have engineered biodegradable nano-polymers (alpha 1–6 polyglucose carboxymethyl sulfate) mimicking (RGTA®) to replace destroyed HS in the damaged ECM scaffolding and to protect cytokines produced by healthy neighbouring cells, thereby restoring the ECM microenvironment and tissue homeostasis and, if needed, provide a homing niche for cell therapy. This matrix therapy approach has considerably improved the quality of healing in various animal models, including muscle and tendon, with reduction or absence of fibrosis resulting in a regeneration process. Over 50 000 patients have been treated in the last years for skin and corneal wounds with dedicated products based on this technology. A randomized controlled trial was performed on 22 racing French Standardbred Trotters (ST) horses to evaluate the efficacy of another polymer, OTR4131 Equitend®, to treat tendinopathies. We evaluated the effect versus placebo on acute superficial digital flexor tendonitis over 4 months by clinical and ultrasonographic measures and their racing performances followed up over the 2 years after treatment. A significant reduction on tendon cross section area was measured in treated animals, racing was 2–3 times more often than placebo, with 3.3 times fewer recurrences and pre-injury performance level was maintained. This study may pave the way for development in humans

Introduction. Osteonecrosis (ON) is one of the most debilitating skeletal disorders. Most patients with ON of the femoral head eventually require surgery, usually total hip arthroplasty, within a few years of disease onset. Previous reports have shown that alendronate reduces osteoclastic activity and reduces the incidence of femoral head collapse in osteonecrotic hips. A randomized study to examine the ability of alendronate to delay or prevent femoral head collapse was performed. Methods. From June 2005 to December 2006, sixty four patients were enrolled and randomly assigned to alendronate or placebo. Five patients were excluded from the analysis because of their failure to adhere to the study protocol. Disease progression was evaluated using radiographs and magnetic resonance imaging (MRI). Results. While the proportion of patients in the alendronate group who underwent total hip arthroplasty was 13% (4 of 31 patients), the proportion of patients undergoing the procedure in the placebo group was 29% (8 of 28 patients; p=0.22, cumulative incidence between the two groups by log-rank test). As such, there was a numerical reduction in the rate of total hip arthroplasty in the alendronate group compared to placebo that did not achieve statistical significance likely because the study was originally powered to detect a between-group difference based on event rates of 35.7% and 3.4% in the placebo and alendronate groups, respectively. Conclusion. Alendronate treatment shows promise for the treatment of atraumatic osteonecrosis. However, additional studies are needed to confirm our results. Osteotomy or bone grafting still remains the procedure of choice for osteonecrosis of the femoral head prior to collapse. Disclosure. The study was supported in part by Merck Sharp & Dohme (I.A) Corp. Taiwan Branch. All these schools received some financial reimbursement for the study

The goals of perioperative management are to relieve pain, achieve early mobilization after surgery, reduce length of hospital stay, and obtain adequate patient satisfaction. Several treatment options combining systemic analgesics and/or regional analgesia with or without opioids are available for postoperative pain; however, a gold standard has not been established although there is a progressive shift towards multimodal approaches to improve analgesia while minimizing opioid-related side effects. EX-TRA-05 (DAVID-ART) was a randomised, double-blind, parallel, pivotal study, evaluating the analgesic efficacy and safety of the innovative oral combination of dexketoprofen/tramadol 25mg/75mg in comparison with the individual components (tramadol given at the higher dose of 100mg) on moderate to severe acute pain after total hip replacement. Repeated doses of study drug were administered every 8 hours and pain intensity (PI) was to be scored according to a 100mm visual analogue scale (VAS) on a programmed e-diary every 2 hours over a 56-hour period (i.e. along 7 repeated doses). A placebo arm was included at the first administration to validate the pain model. Rescue medication, metamizole 500mg, was available during the treatment period. The study primary endpoint was the mean sum of the pain intensity difference values throughout the first 8 hours (SPID. 8. ), which considered the 3 active treatment arms and placebo (ITT population; N=641). In this phase, a clear superiority of the combination over the single agents was demonstrated (p<0.05). An additional analysis was performed during the entire 0–56h repeated-dose period excluding those patients who had received placebo at the first dose (N=161). The estimated mean (SE) differences on PI-VAS over 24, 32 and 56 hours post first dose (0–24h, 0–32h, and 0–56h) between the combination and each single agent were evaluated. Patients who received active analgesic from the first dose (mITT population; N=480) were aged 29–80 years (42% were ≥65 years). At randomisation, pain was moderate (≥40–60mm) in 51% patients and severe (>60mm) in 49%. For dexketoprofen/tramadol, mean (SD) PI-VAS values were 22 (4.0) over 24 hours; 21 (4.1) over 32 hours; and 19 (3.8) over 56 hours. The estimated differences versus dexketoprofen 25mg and tramadol 100mg were respectively 10 (0.7) and 7.6 (0.7) over 24 hours; 9.8 (0.6) and 7.2 (0.6) over 32 hours; and 8.1 (0.5) and 6.3 (0.5) over 56 hours (p<0.0001 for all comparisons), which confirmed the superiority of the combination versus both single agents throughout the periods analysed. This significant higher decrease of PI favouring dexketoprofen/tramadol 25mg/75mg over dexketoprofen 25mg and tramadol 100mg, all given every 8 hours, during the first 56 hours post dose confirmed the superior analgesia shown after the first 0–8h post-dose period. The combination of dexketoprofen/tramadol 25mg/75mg is able to provide a level of analgesia above that achievable by each component alone, with a sustained effect when used as a multiple-dose regimen. The addition of this new combo to the analgesic armamentarium may contribute to facilitate early mobilization after surgery, thus positively impacting perioperative co-morbidities and length of in-hospital stay

INTRODUCTION. Endochondral ossification in the growth plate is directly responsible for skeletal growth and its de novo bone-generating activity. Growth plates are vulnerable to disturbances that may lead to abnormal skeletal development. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics but have been reported to impair endochondral ossification-driven fracture healing. Despite the general awareness that NSAIDs affect endochondral ossification, the consequences of NSAIDs on skeletal development are unknown. We hypothesise that the NSAID celecoxib leads to impaired growth plate development and consequently impairs skeletal development. METHODS. Healthy skeletally immature (5 weeks old) C57BL/6 mice were treated for ten weeks with celecoxib (daily oral administration 10 mg/kg) or placebo (water) (institutional approval 2013–094) (n=12 per group). At 15 weeks postnatally, total growth plate thickness, the thickness of specific growth plate zones, (immuno)histological analysis of extracellular matrix composition in the growth plate, cell number and cell size, longitudinal bone growth and bone micro-architecture by micro-CT were analysed. Inhibition of COX-2 activity was confirmed by determining PGE2 levels in plasma using an ELISA. RESULTS. No significant difference in total growth plate thickness or thickness of the resting zone, proliferative or hypertrophic zone was found between groups. Staining of growth plate extracellular matrix components revealed, however, a significantly higher proteoglycan content and less collagen type II staining in the proliferative zone. In the hypertrophic zone of the growth plates of celecoxib treated mice collagen type X was hardly detectable as compared to placebo mice. In addition, a significantly decreased cell number was observed in the hypertrophic zone of the growth plate and cells were significantly smaller in the celecoxib group. Micro-CT analysis of the subchondral bone region directly beneath the growth plate showed significantly higher bone density, bone volume density and trabecular thickness following celecoxib treatment. Despite the detected differences in extracellular matrix composition of the growth plate, no difference was found in the length of the tibia in celecoxib treated mice. DISCUSSION. In summary, there are no measurable differences found in murine skeletal formation as a result of treatment with celecoxib in this study. However, there are notable phenotypic features found in the maturation of the growth plate (hypertrophic zone and subchondral bone) as a result from the celecoxib treatment, of which the potential consequences we do not yet understand. SIGNIFICANCE. When follow-up actions from the use of celecoxib on the growing individual are found this may warrant re-evaluation for the use of celecoxib in these individuals

This study aims to investigate that a single dose of tranexamic acid (TXA) will reduce blood loss and transfusion rates in elderly patients, undergoing intertrochanteric (IT) or femoral neck fractures surgery. Consecutive elderly patients receiving hip fracture surgery for stable or unstable IT fracture, treated with short intramedullary nail (IMN) insertion as well as cemented hemiarthroplasty for acute femoral neck (subcapital) hip fracture, were screened for inclusion in this single-centre randomized trial. Patients were randomly allocated to a study group by sealed envelope. One TXA dose of 15 mg/kg i.v. diluted in 100 ml N/S or one placebo dose i.v. in 100 ml N/S were administered 5 mins before the skin cut. Haemoglobin (Hb) concentration was measured at admission time and prior to surgery. Post-operatively it was measured on a daily basis until day 4, giving a total of four Hb measurements (days 1 to 4). The transfusion trigger point was determined in accordance with the French guidelines for erythrocyte blood transfusion. The transfusion trigger was 10 g/dl for patients at risk, while in all other cases, it was 9 g/dl. Information regarding the transfusions number was assessed directly by the hospital blood bank database. Blood loss was calculated by the Hb dilution method. Nadler's formula was used to calculate patients' blood volume. For calculation of total blood loss (TBL) expressed to total Hb loss and total Volume loss, the number of transfusions (55 grams of Hb per transfusion), the Hb concentration on preoperatively (Hgbi) and the Hb concentration on the last measure (Hgbe) were used. (Hb balance method). The primary efficacy outcome was the number of transfusions of allogeneic RBC from surgery up to day 4. The secondary ones were the total blood loss from surgery to day 4 as it was calculated by Hb-balance method. After randomization, 35 patients with femoral neck fracture and 30 patients with IT fracture received TXA prior to surgery. Respectively, 30 patients with femoral neck fracture and 55 with IT fracture didn't receive TXA. The groups did not differ significantly in their basic demographics (age, gender, BMI, injury mechanism, ASA score, co-morbidities). Results showed that patients undergoing hemiarthroplasty after receiving TXA, were transfused with less allogeneic RBC and had less total blood loss than patients that didn't receive TXA, but without statistical significance. While patients treated with IMN in the TXA group received a significantly lower number of RBC units than the control group (1.28 ± 1.049 vs 2.075 ± 1.685), (P = 0.0396), had a significantly lower loss of Hb (98.59 ± 55.24 vs 161.6 ± 141.7), (P = 0.0195) and a lower total blood volume loss (951.3 ± 598.9 ml vs 1513 ± 1247 ml), (P = 0.023). This trial confirmed TXA administration efficacy in reducing blood loss and transfusion rate in elderly patients undergoing hip fracture surgery. A TXA single dose may be a safer option, taking into account these patients' physiological status and co-morbidities

Background. Osteoarthritis (OA) pain treatment has limitations in terms of serious adverse effects and low efficacy. We aimed to evaluate efficacy and safety of naproxen sodium/codeine phosphate combination in these patients. Methods. In this prospective, randomised, double blind, placebo controlled clinical trial, 135 patients with osteoarthritis, who were 40–65 years; applied to our institution's orthopaedics outpatient clinic; had grade 1, 2, or 3 primary osteoarthritis diagnosed in last 1 year; and had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score≥40, and Visual Analogue Scale score≥40, were enrolled. Subjects were randomised (1:1) to placebo (n= 67) or combination (n= 68) arms, in which 550 mg naproxen sodium/30mg codeine phosphate was given orally twice a day for 7 days. Rescue medicine was 500 mg paracetamol (max= 6 tablets/day). Demographic characteristics, medical history, adverse events, VAS and WOMAC scores were collected in study visits performed within 10 days. The study was approved by local institutional ethics committee and written informed consents were obtained from all participants. Results. Patients were evenly matched in both arms. The mean age was 52.3±6.6 years (89.7% female). WOMAC and VAS scores decreased significantly within each group (p<0.001 for all). For the study group (n=43) the mean (+ SD) and median (min-max) VAS Score was −29.8 (+21.0) and −30 (−70−0), respectively. In contrast, for the control group (n=36) the mean and median (min-max) VAS Score was −16.1 (+24.4) and −12.5 (−65−40), respectively. WOMAC score was decreased more in combination group (p= 0.044). Changes in VAS scores between visits were significantly different (more in combination receivers) between groups (p= 0.018). Ratio of patients requiring no rescue medicine was higher among combination receivers than controls (64.8% vs. 35.2%, respectively). Most common adverse events were constipation, dyspepsia, and somnolence; no fatality was encountered. Conclusions. Naproxen sodium/codeine phosphate combination is effective and safe in osteoarthritis patients. Level of Evidence. Level 1

The Cochrane Collaboration has produced three new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner. These are relevant to a wide range of musculoskeletal specialists, and include reviews in lateral elbow pain, osteoarthritis of the big toe joint, and cervical spine injury in paediatric trauma patients.

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

The objective of this trial was to investigate the efficacy of a Comfrey root extract cream in patients with acute upper or lower back pain. The study was conducted as a double-blind, multi-centre, parallel group design RCT over a period of 5 ± 1 days. The patients (n=120, mean age 36.9 years, 46.7 % female) were treated three times a day, 4 g cream per application. The trial included four visits. The primary efficacy variable was the area-under-the-curve (AUC) of the Visual Analogue Scale (VAS) on active standardised movement values at visits 1 to 4. Among the secondary objectives were back pain at rest (VAS), pressure algometry (pain-time curve; AUC over 5 days), global assessment of efficacy by the patient and investigator, and functional impairment measured with the Oswestry Disability Index. There was a significant treatment difference between verum and placebo. In the course of the trial the primary variable decreased on average (median) about 95,2 % in the Comfrey extract group and 37.8 % in the placebo group. The results separated by pain location show an equivalent effect of comfrey extract: Regarding pain at rest, in lower back pain a reduction of 98% were observed, in upper back pain 96.9%. The results of this RCT were clear-cut and consistent across all variables. Comfrey root extract cream showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 hour) was also witnessed in this trial. Conflicts of interest and sources of funding. CS and MT are employees of Merck Selbstmedikation GmbH, the sponsor of the presented clinical trial. BMG is CEO of CRM Pharmaberatung GmbH, the CRO of the presented clinical trial

The postoperative course of median nerve decompression in the carpal tunnel syndrome may sometimes be complicated by postoperative pain, paresthesias, and other unpleasant symptoms, or be characterized by a slow recovery of nerve function due to prolonged preoperative injury causing extensive nerve damage. The aim of this study is to explore any possible effects of alpha lipoic acid (ALA) in the postoperative period after surgical decompression of the median nerve at the wrist. Patients were enrolled with proven carpal tunnel syndrome and randomly assigned into one of two groups: Group A: surgical decompression of the median nerve followed by ALA for 40 days. Group P: surgical decompression followed by placebo. The primary endpoint of the study was nerve conduction velocity at 3 months post surgery, Other endpoints were static 2 point discrimination, the Boston score for hand function, pillar pain and use of pain killers beyond the second postoperative day. ALA did not show to significantly improve nerve conduction velocity or Boston score. However, a statistically significant reduction in the postoperative incidence of pillar pain was noted in Group A. In addition, static 2 point discrimination showed to be significantly improved by ALA. Administration of ALA following decompression of the median nerve for carpal tunnel release is effective on nerve recovery, although this is not detectable through nerve conduction studies but in terms of accelerated and improved static two-point discrimination. The use of ALA as a supplementation for nerve recovery after surgical decompression may be extended to all types of compression syndromes or conditions where a nerve is freed from a mechanical insult. Furthermore, ALA limits post-decompression pain, including late pericicatricial pain at the base of the palm, the so called pillar pain, which seems to be associated with a reversible damage to the superfical sensitive small nerve fibers. In conclusion postoperative administration of ALA for 40 days post-median nerve decompression was positively associated with nerve recovery, induced a lower incidence of postoperative pillar pain and was associated with a more rapid improvement of static two-point discrimination. This treatment is well tolerated and associated with high levels of satisfaction and compliance, supporting its value as a standard postoperative supplementation after carpal tunnel decompression

Aims. A systematic review of the available literature comparing the outcomes of radiofrequency denervation to sham procedure in treating chronic low back pain caused by lumber zygapophysial joint pathology. Methods. Medline and EMBASE databases were searched for English language articles from 2005 to July 2010. Articles were considered for review if they satisfied the inclusion criteria: Randomised Controlled Trials(RCT) comparing radiofrequency neurotomy(RFN) to a ‘placebo’ procedure in patients with chronic low back pain caused by facet joint osteoarthritis. Adult patients of both sexes above 17 years of age who complained of continuous low back pain for more than 6 months with focal tenderness over the facet joints. Outcome measures of interest are pain improvement, physical activity, analgesic use, quality of life variables, range of motion of the lumbar spine and hip movement. Critical appraisal of the selected studies was carried out using the CASP appraisal tool for RCT. Results. Two articles were identified. Both demonstrated a statistically significant improvement in the pain (p<0.05) using a visual analogue scale in the RFN group compared to the sham procedure. Only one trial demonstrated a corresponding reduction in analgesic use. There was no consensus of improvement of quality of life factors in either study as compared to placebo. Conclusion. Radiofrequency denervation is better than sham procedure in treating pain caused by facet joint osteoarthritis with minimal adverse effects in the short term. A higher powered trial using a larger cohort and longer follow up is required to resolve some of the equivocal results. Conflicts of Interest. None. Source of Funding. None