Aims. The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone. Methods. This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group. Results. We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups. Conclusion. The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications. Cite this article: Bone Joint J 2024;106-B(8):849–857

There is increasing evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can adversely affect bone repair. We have, therefore, studied the in vitro effects of NSAIDs, which differentially inhibit cyclooxygenases (COX), the prostaglandin/thromboxane synthesising enzymes, on human osteoblasts. Indomethacin and the new nitric oxide (NO)-donating NSAIDs block the activity of both COX-1 and COX-2. Indomethacin and 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulphonal) phenyl-2 (5H)-furanone (DFU) reduced osteoblast numbers in a dose-dependant manner and increased collagen synthesis and alkaline phosphatase activity. The reduction in osteoblast numbers was not caused by loss of adhesion and was reversible. Neither NSAID influenced DNA synthesis. There was no difference between the effects of indomethacin and DFU. NO-NSAIDs did not affect cell numbers. These results suggest that care should be taken when administering NSAIDs to patients with existing skeletal problems and that NO-NSAIDs may be safer

Aims. Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries. Methods. This multicentre case-control study comprised 200 patients with post-traumatic elbow HO and 229 patients who had elbow trauma but without HO formation between July 2019 and December 2020. Features possibly associated with HO formation were obtained. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariable logistic regression analysis was applied to build the new nomogram: the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction model (STEHOP). STEHOP was validated by concordance index (C-index) and calibration plot. Internal validation was conducted using bootstrapping validation. Results. Male sex, obesity, open wound, dislocations, late definitive surgical treatment, and lack of use of non-steroidal anti-inflammatory drugs were identified as adverse predictors and incorporated to construct the STEHOP model. It displayed good discrimination with a C-index of 0.80 (95% confidence interval 0.75 to 0.84). A high C-index value of 0.77 could still be reached in the internal validation. The calibration plot showed good agreement between nomogram prediction and observed outcomes. Conclusion. The newly developed STEHOP model is a valid and convenient instrument to predict HO formation after surgery for elbow trauma. It could assist clinicians in counselling patients regarding treatment expectations and therapeutic choices. Cite this article: Bone Joint J 2022;104-B(8):963–971

Aims. It is common practice for patients to have postoperative blood tests after total joint replacement (TJR). However, there have been significant improvements in perioperative care with arthroplasty surgery, and a drive to reduce the length of stay (LOS) and move towards day-case TJR. We should reconsider whether this intervention is necessary for all patients. Methods. This retrospective study included all patients who underwent a primary unilateral TJR at a single tertiary arthroplasty centre during a one-year period. Electronic medical records of 1,402 patients were reviewed for patient demographics, LOS, and American Society of Anesthesiologists (ASA) grade. Blood tests were examined to investigate the incidence of postoperative anaemia, electrolyte abnormalities, and incidence of acute kidney injury (AKI). Results. For total knee arthroplasties, preoperative (R = −0.22) and postoperative haemoglobin (R = 0.2) levels were both negatively correlated with LOS (p < 0.001). For all patients who had undergone a TJR, 19 patients (0.014%) required a blood transfusion postoperatively due to symptomatic anaemia. Risk factors identified were age, preoperative anaemia, and long-term aspirin use. Significant abnormal sodium levels were found in123 patients (8.7%). However, only 36 patients (2.6%) required intervening treatment. Risk factors identified were age, preoperative abnormal sodium level, and long-term use of non-steroidal anti-inflammatory drugs, angiotensin receptor blockers, and corticosteroids. Similarly, abnormal potassium levels were evident in 53 patients (3.8%), and only 18 patients (1.3%) required intervening treatment. Risk factors identified were preoperative abnormal potassium level, and long-term use of angiotensin-converting enzyme inhibitors and diuretics. The incidence of AKI was 4.4% (61 patients). Risk factors identified were age, increased ASA grade, preoperative abnormal sodium, and creatinine level. Conclusion. Routine blood tests after primary TJR is unnecessary for most patients. Blood tests should only be performed on those with identifiable risk factors such as preoperative anaemia and electrolyte abnormalities, haematological conditions, long-term aspirin use, and electrolyte-altering medications. Cite this article: Bone Jt Open 2023;4(5):357–362

Aims. The primary aim of this study was to identify independent predictors associated with nonunion and delayed union of tibial diaphyseal fractures treated with intramedullary nailing. The secondary aim was to assess the Radiological Union Scale for Tibial fractures (RUST) score as an early predictor of tibial fracture nonunion. Methods. A consecutive series of 647 patients who underwent intramedullary nailing for tibial diaphyseal fractures were identified from a trauma database. Demographic data, comorbidities, smoking status, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and steroid use were documented. Details regarding mechanism of injury, fracture classification, complications, and further surgery were recorded. Nonunion was defined as the requirement for revision surgery to achieve union. Delayed union was defined as a RUST score < 10 at six months postoperatively. Results. There were 41 nonunions (6.3%), of which 13 were infected (31.7%), and 77 delayed unions (11.9%). There were 127 open fractures (19.6%). Adjusting for confounding variables, NSAID use (odds ratio (OR) 3.50; p = 0.042), superficial infection (OR 3.00; p = 0.026), open fractures (OR 5.44; p < 0.001), and high-energy mechanism (OR 2.51; p = 0.040) were independently associated with nonunion. Smoking (OR 1.76; p = 0.034), open fracture (OR 2.82; p = 0.001), and high-energy mechanism (OR 1.81; p = 0.030) were independent predictors associated with delayed union. The RUST score at six-week follow-up was highly predictive of nonunion (sensitivity and specificity of 75%). Conclusion. NSAID use, high-energy mechanisms, open fractures, and superficial infection were independently associated with nonunion in patients with tibial diaphyseal fractures treated with intramedullary nailing. The six-week RUST score may be useful in identifying patients at risk of nonunion. Cite this article: Bone Jt Open 2021;2(4):227–235

Aims. The aim of this study was to assess the efficacy of non-selective and selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing heterotopic ossification (HO) after total hip arthroplasty (THA). Methods. A thorough and systematic literature search was conducted and 29 studies were found that met inclusion criteria. Data were extracted and statistical analysis was carried out generating forest plots. Results. Non-selective NSAIDs showed a significant decrease in the odds for forming HO after THA (odds ratio (OR) -1.35, confidence interval (CI) -1.83 to -0.86) when compared with placebo. Selective NSAIDs also showed a significant decrease in the odds for forming HO after THA when compared with placebo (OR -1.58, CI -2.41 to -0.75). When comparing non-selective NSAIDs with selective NSAIDs, there was no significant change in the odds for forming HO after THA (OR 0.22, CI -0.36 to 0.79). Conclusion. Our meta-analyses of all available data suggest that both non-selective and selective NSAIDs are effective HO prophylaxis and can be used routinely after THA for pain control as well as prevention of HO. Indomethacin may serve as the benchmark among non-selective NSAIDs and celecoxib among selective NSAIDs. There was no difference in the incidence of HO between non-selective and selective NSAIDs, allowing physicians to choose either based on the clinical scenario and patient-specific factors. Cite this article: Bone Joint J 2018;100-B:915–22

Aims. The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects. Methods. In this pilot study, buccal samples were collected from 31 primary TKA patients. Pharmacogenetics testing examined genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of non-steroidal anti-inflammatory drugs and opioids. We examined the frequency of genetic variants to any of the medications we prescribed including celecoxib, hydrocodone, and tramadol. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen, and the study group received a customized regimen based on the pharmacogenetic results. For the first ten postoperative days, patients recorded pain scores, medication, and side effects. Results. Genetic variants involving one or more medications in the multimodal pain protocol occurred in 13 of the 31 patients (42%). In total, eight patients (26%) had variants affecting more than one of the medications. For the 25 patients who recorded pain and medication logs, the mean pain levels and morphine equivalents (MEQs) consumed in the first ten days were higher in the control group than in the custom-guided group (p = 0.019 for pain and p = 0.655 for MEQ). Conclusion. Overall, 42% of patients had a variant involving one of the pain medications prescribed in our perioperative pain program for TKA. Ongoing research will help determine if using these data to modify a patient’s medication will improve outcomes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):73–78

We analysed which pre-operative factors could be used to predict the length of in-patient stay following unilateral primary total hip replacement undertaken for osteoarthritis. Data were collected prospectively from 2302 patients undergoing primary total hip replacement over a nine-year period. The relationships between the various pre-operative factors and length of stay were studied separately using either Student’s t-test or Pearson’s correlation, and then subjected to multiple linear regression analysis. The mean length of stay was 8.1 days (median 7; 3 to 58). After adjusting for the effects of other pre-operative factors, younger age, male gender, higher combined Harris hip function and activity score, higher general health perception dimension of the Short-Form 36 score, and non-steroidal anti-inflammatory drug use were all found to be significantly associated with a reduced length of stay

Objectives. Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model. Methods. A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats. A ‘parecoxib immediate’ (Pi) group received parecoxib (3.2 mg/kg bodyweight twice per day) on days 0, 1, and 2. A ‘parecoxib delayed’ (Pd) group received the same dose of parecoxib on days 3, 4, and 5. A control group received saline only. Fracture healing was evaluated by biomechanical tests, histomorphometry, and dual-energy x-ray absorptiometry (DXA) at four weeks. Results. For ultimate bending moment, the median ratio between fractured and non-fractured tibia was 0.61 (interquartile range (IQR) 0.45 to 0.82) in the Pi group, 0.44 (IQR 0.42 to 0.52) in the Pd group, and 0.50 (IQR 0.41 to 0.75) in the control group (n = 44; p = 0.068). There were no differences between the groups for stiffness, energy, deflection, callus diameter, DXA measurements (n = 64), histomorphometrically osteoid/bone ratio, or callus area (n = 20). Conclusion. This study demonstrates no negative effect of immediate or delayed short-term administration of parecoxib on diaphyseal fracture healing in rats. Cite this article: G. A. Hjorthaug, E. Søreide, L. Nordsletten, J. E. Madsen, F. P. Reinholt, S. Niratisairak, S. Dimmen. Short-term perioperative parecoxib is not detrimental to shaft fracture healing in a rat model. Bone Joint Res 2019;8:472–480. DOI: 10.1302/2046-3758.810.BJR-2018-0341.R1

We have carried out a prospective double-blind randomised controlled trial to compare the efficacy of a single subacromial injection of the non-steroidal anti-inflammatory drug, tenoxicam, with a single injection of methylprednisolone in patients with subacromial impingement. A total of 58 patients were randomly allocated into two groups. Group A received 40 mg of methylprednisolone and group B 20 mg of tenoxicam as a subacromial injection along with lignocaine. The Constant-Murley shoulder score was used as the primary outcome measure and the Disability of Arm, Shoulder and Hand (DASH) and the Oxford Shoulder Score (OSS) as secondary measures. Six weeks after injection the improvement in the Constant-Murley score was significantly greater in the methylprednisolone group (p = 0.003) than in the tenoxicam group. The improvement in the DASH score was greater in the steroid group and the difference was statistically significant and consistent two (p < 0.01), four (p < 0.01) and six weeks (p < 0.020) after the injection. The improvement in the OSS was consistently greater in the steroid group than in the tenoxicam group. Although the difference was statistically significant at two (p < 0.001) and four (p = 0.003) weeks after the injection, it was not at six weeks (p = 0.055). Subacromial injection of tenoxicam does not offer an equivalent outcome to subacromial injection of corticosteroid at six weeks. Corticosteroid is significantly better than tenoxicam for improving shoulder function in tendonitis of the rotator cuff after six weeks

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel. In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing. Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib

We report four patients with unilateral postpartum sacroiliitis presenting with agonising unilateral pain, an elevated ESR, elevated alkaline phosphatase levels, leucocytosis and positive bone scans. The diagnosis of a non-infectious inflammatory cause was supported by the postpartum onset, the response to non-steroidal anti-inflammatory drugs, negative aspiration cultures in two cases and the lack of changes in the sacroiliac joints on long-term follow-up radiographs

Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones

We report a prospective, randomised, controlled trial of the effect of either a non-steroidal anti-inflammatory drug (diclofenac sodium) or physiotherapy on the recovery of knee function after arthroscopy. At 42 days after surgery there was no significant benefit from either form of postoperative treatment compared with the control group. Complications attributable to the anti-inflammatory drug occurred in 9.6% of the patients so treated. Neither the routine administration of a non-steroidal anti-inflammatory agent nor routine physiotherapy is justified after arthroscopy of the knee

We investigated the clinical response to arthroscopic synovectomy in patients with undifferentiated chronic monoarthritis (UCMA) of the wrist. Arthroscopic synovectomy was performed on 20 wrists in 20 patients with UCMA of the wrist who had not responded to non-steroidal anti-inflammatory drugs. The mean duration of symptoms at the time of surgery was 4.3 months (3 to 7) and the mean follow-up was 51.8 months (24 to 94). Inflamed synovium was completely removed from the radiocarpal, midcarpal and distal radioulnar joints using more portals than normal. After surgery, nine patients had early remission of synovitis and 11 with uncontrolled synovitis received antirheumatic medication. Overall, there was significant improvement in terms of pain relief, range of movement and Mayo score. Radiological deterioration was seen in five patients who were diagnosed as having rheumatoid arthritis during the follow-up period. Lymphoid follicles and severe lymphocyte infiltration were seen more often in synovial biopsies from patients with uncontrolled synovitis. These results suggest that arthroscopic synovectomy provides pain relief and functional improvement, and allows rapid resolution of synovitis in about half of patients with UCMA of the wrist

We studied the effect of non-steroidal anti-inflammatory drugs on the fixation of hydroxyapatite-coated implants. Cylindrical plugs of pure titanium, coated with hydroxyapatite (HA), were inserted into both femora of 10 adult rabbits, 5 of which received 7 daily doses of 30 mg diclofenac. Three weeks after implantation the interface strengths were measured by the pull-out test. The mean peak force for the diclofenac-treated group was 290 +/- 57 N compared with 369 +/- 37 N for the control group (p < 0.025). We conclude that the inhibitory effect of diclofenac on bone repair is not neutralised by HA-coating of an implant

We studied the safety of combining the postoperative use of a non-steroidal anti-inflammatory drug with low-dose heparin. In a double-blind, placebo-controlled clinical trial we reviewed the complications in 235 patients after total hip replacement, all treated with low-dose heparin and either indomethacin or a placebo. The incidence and type of complications in the two groups were nearly equal; indomethacin-treated patients had no increase in complications related to bleeding. Postoperative bleeding into drains was marginally greater in the indomethacin group, although the difference was not statistically significant. We conclude that treatment with indomethacin and low-dose heparin after hip replacement does not significantly increase the bleeding or other complications. We also found that patients receiving indomethacin were mobilised an average of one day before those on placebo

Tuberculous osteomyelitis which does not involve a joint is uncommon and may fail to be diagnosed by an orthopaedic surgeon. We treated 28 lesions of tuberculous osteomyelitis in 25 patients between 1988 and 1995. The duration of symptoms was from two to 39 months, and most of our patients had been treated initially with non-steroidal anti-inflammatory drugs which failed to provide relief. Bone pain which does not promptly respond to analgesic medication is often due to infection or neoplasia. In the early stages, when plain radiographs are normal, MRI or CT may help to localise lesions. On plain radiographs, more advanced lesions may mimic chronic pyogenic osteomyelitis, Brodie’s abscess, tumours or granulomatous lesions. Biopsy is mandatory to confirm the diagnosis, and antituberculous drugs are the mainstay of treatment. When operative findings at biopsy have the features of skeletal tuberculosis curettage of the affected bone may promote earlier healing

We assessed factors which may affect union in 32 patients with nonunion of a fracture of the diaphysis of the femur and 67 comparable patients whose fracture had united. These included gender, age, smoking habit, the use of non-steroidal anti-inflammatory drugs (NSAIDs) the type of fracture (AO classification), soft-tissue injury (open or closed), the type of nail, the mode of locking, reaming v non-reaming, infection, failure of the implant, distraction at the fracture site, and the time to full weight-bearing. Patients with severe head injuries were excluded. Both groups were comparable with regard to gender, Injury Severity Score and soft-tissue injury. There was no relationship between the rate of union and the type of implant, mode of locking, reaming, distraction or smoking. There were fewer cases of nonunion in more comminuted fractures (type C) and in patients who were able to bear weight early. There was a marked association between nonunion and the use of NSAIDs after injury (p = 0.000001) and delayed healing was noted in patients who took NSAIDs and whose fractures had united