Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Osteoid osteoma is treated primarily by radiofrequency (RF) ablation. However, there is little information about the distribution of heat in bone during the procedure and its safety. We constructed a model of osteoid osteoma to assess the distribution of heat in bone and to define the margins of safety for ablation. Cavities were drilled in cadaver bovine bones and filled with a liver homogenate to simulate the tumour matrix. Temperature-sensing probes were placed in the bone in a radial fashion away from the cavities. RF ablation was performed 107 times in tumours < 10 mm in diameter (72 of which were in cortical bone, 35 in cancellous bone), and 41 times in cortical bone with models > 10 mm in diameter. Significantly higher temperatures were found in cancellous bone than in cortical bone (p <  0.05). For lesions up to 10 mm in diameter, in both bone types, the temperature varied directly with the size of the tumour (p < 0.05), and inversely with the distance from it. Tumours of > 10 mm in diameter showed a trend similar to those of smaller lesions. No temperature rise was seen beyond 12 mm from the edge of a cortical tumour of any size. Formulae were developed to predict the expected temperature in the bone during ablation.

Cite this article: Bone Joint J 2014; 96-B:677–83

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus.

Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells.

In conclusion, it should not be assumed that degenerative changes always precede disc herniation.

Cite this article: Bone Joint J 2013;95-B:1127–33.

Pain, swelling and inflammation are expected during the recovery from total knee arthroplasty (TKA) surgery. The severity of these factors and how a patient copes with them may determine the ultimate outcome of a TKA. Cryotherapy and compression are frequently used modalities to mitigate these commonly experienced sequelae. However, their effect on range of motion, functional testing, and narcotic consumption has not been well-studied.

A prospective, multi-center, randomised trial was conducted to evaluate the effect of a cryopneumatic device on post-operative TKA recovery. Patients were randomised to treatment with a cryopneumatic device or ice with static compression. A total of 280 patients were enrolled at 11 international sites. Both treatments were initiated within three hours post-operation and used at least four times per day for two weeks. The cryopneumatic device was titrated for cooling and pressure by the patient to their comfort level.

Patients were evaluated by physical therapists blinded to the treatment arm. Range of motion (ROM), knee girth, six minute walk test (6MWT) and timed up and go test (TUG) were measured pre-operatively, two- and six-weeks post-operatively. A visual analog pain score and narcotic consumption was also measured post-operatively.

At two weeks post-operatively, both the treatment and control groups had diminished ROM and function compared to pre-operatively. Both groups had increased knee girth compared to pre- operatively. There was no significant difference in ROM, 6MWT, TUG, or knee girth between the 2 groups. We did find a significantly lower amount of narcotic consumption (509 mg morphine equivalents) in the treatment group compared with the control group (680 mg morphine equivalents) at up to two weeks postop, when the cryopneumatic device was being used (p < 0.05). Between two and six weeks, there was no difference in the total amount of narcotics consumed between the two groups. At six weeks, there was a trend toward a greater distance walked in the 6MWT in the treatment group (29.4 meters versus 7.9 meters, p = 0.13). There was a significant difference in the satisfaction scores of patients with their cooling regimen, with greater satisfaction in the treatment group (p < 0.0001). There was no difference in ROM, TUG, VAS, or knee girth at six weeks. There was no difference in adverse events or compliance between the two groups.

A cryopneumatic device used after TKA appeared to decrease the need for narcotic medication from hospital discharge to 2 weeks post-operatively. There was also a trend toward a greater distance walked in the 6MWT. Patient satisfaction with the cryopneumatic cooling regimen was significantly higher than with the control treatment.

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.

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases.

This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry.

Cite this article: Bone Joint J 2013;95-B:305–13.

No previous studies have examined the physical characteristics of patients with cauda equina syndrome (CES). We compared the anthropometric features of patients who developed CES after a disc prolapse with those who did not but who had symptoms that required elective surgery. We recorded the age, gender, height, weight and body mass index (BMI) of 92 consecutive patients who underwent elective lumbar discectomy and 40 consecutive patients who underwent discectomy for CES. On univariate analysis, the mean BMI of the elective discectomy cohort (26.5 kg/m² (16.6 to 41.7) was very similar to that of the age-matched national mean (27.6 kg/m², p = 1.0). However, the mean BMI of the CES cohort (31.1 kg/m² (21.0 to 54.9)) was significantly higher than both that of the elective group (p < 0.001) and the age-matched national mean (p < 0.001). A similar pattern was seen with the weight of the groups. Multivariate logistic regression analysis was performed, adjusted for age, gender, height, weight and BMI. Increasing BMI and weight were strongly associated with an increased risk of CES (odds ratio (OR) 1.17, p < 0.001; and OR 1.06, p <  0.001, respectively). However, increasing height was linked with a reduced risk of CES (OR 0.9, p < 0.01). The odds of developing CES were 3.7 times higher (95% confidence interval (CI) 1.2 to 7.8, p = 0.016) in the overweight and obese (as defined by the World Health Organization: BMI ≥ 25 kg/m²) than in those of ideal weight. Those with very large discs (obstructing > 75% of the spinal canal) had a larger BMI than those with small discs (obstructing < 25% of the canal; p < 0.01). We therefore conclude that increasing BMI is associated with CES.

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87).

All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance.

Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient’s local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.

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 describe a series of 20 patients with ununited fractures of the femoral neck following neglected trauma or failed primary internal fixation who were seen at a mean of 7.5 months (2 to 18) following injury. Open reduction and internal fixation of the fracture was performed in all patients, together with a myoperiosteal flap on the quadratus femoris muscle pedicle.

Union occurred at a mean of 4.9 months (2 to 10) in all patients. The mean follow-up was for 70 months (14 to 144). There was no further progression in six of seven patients with pre-operative radiological evidence of osteonecrosis of the femoral head. One patient had delayed collapse and flattening of the femoral head ten years after union of the fracture, but remained asymptomatic.

This study demonstrates the orthopaedic application of myoperiosteal grafting for inducing osteogenesis in a difficult clinical situation.

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p > 0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p < 0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p > 0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p < 0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p > 0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p < 0.05).

Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.