We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment.

The use of intramedullary nails prevented recurrence of deformity and refracture.

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair.

Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1^+/−) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection.

When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1^+/− mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07).

These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1.

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.

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions.

Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation.

Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future.

Cite this article: Bone Joint J 2014; 96-B: 569–73.

The June 2014 Children’s orthopaedics Roundup³⁶⁰ looks at: plaster wedging in paediatric forearm fractures; the medial approach for DDH; Ponseti – but not as he knew it?; Salter osteotomy more accurate than Pemberton in DDH; is the open paediatric fracture an emergency?; bang up-to-date with femoral external fixation; indomethacin, heterotopic ossification and cerebral palsy hips; lengthening nails for congenital femoral deformities, and is MRI the answer to imaging of the physis?

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting. There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone

Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture.

We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery.

The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2).

A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

Cite this article: Bone Joint J 2014;96-B:658–64.

Using human cadaver specimens, we investigated the role of supplementary fibular plating in the treatment of distal tibial fractures using an intramedullary nail. Fibular plating is thought to improve stability in these situations, but has been reported to have increased soft-tissue complications and to impair union of the fracture. We proposed that multidirectional locking screws provide adequate stability, making additional fibular plating unnecessary. A distal tibiofibular osteotomy model performed on matched fresh-frozen lower limb specimens was stabilised with reamed nails using conventional biplanar distal locking (CDL) or multidirectional distal locking (MDL) options with and without fibular plating. Rotational stiffness was assessed under a constant axial force of 150 N and a superimposed torque of ± 5 Nm. Total movement, and neutral zone and fracture gap movement were analysed.

In the CDL group, fibular plating improved stiffness at the tibial fracture site, albeit to a small degree (p = 0.013). In the MDL group additional fibular plating did not increase the stiffness. The MDL nail without fibular plating was significantly more stable than the CDL nail with an additional fibular plate (p = 0.008).

These findings suggest that additional fibular plating does not improve stability if a multidirectional distal locking intramedullary nail is used, and is therefore unnecessary if not needed to aid reduction.

Cite this article: Bone Joint J 2014;96-B:385–9.

The August 2012 Research Roundup³⁶⁰ looks at: PRP and chondrogenic differentiation; basic fibroblast growth factor; whether glucosamine works; randomised trials; ossification of the ligamentum flavum; treadmill running; inhibiting BMP antagonists; and whether NSAIDs delay union after all.

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36

This preliminary study evaluates a combination of bone morphogenetic protein (BMP)-7 and non-vascularised autologous fibular grafting (AFG) for the treatment of osteonecrosis of the femoral head.

BMP-7/AFG combination was applied in seven pre-collapse femoral heads (five Steinberg stage II, two stage III) in six patients. Pre- and post-operative evaluation included clinical (Harris hip score (HHS), visual analogue scale (VAS) for pain) and radiological assessment (radiographs, quantitative CT) at a mean follow-up of 4 years (2 to 5.5).

A marked improvement of function (mean HHS increase of 49.2) and decrease of pain level (mean VAS decrease of 5) as well as retention of the sphericity of the femoral head was noted in five hips at the latest follow-up, while signs of consolidation were apparent from the third post-operative month. One patient (two hips) required bilateral total hip replacement at one year post-operatively. In the series as a whole, quantitative-CT evaluation revealed similar densities between affected and normal bone. Heterotopic ossification was observed in four hips, without compromise of the clinical outcome.

In this limited series AFG/BMP-7 combination proved a safe and effective method for the treatment of femoral head osteonecrosis, leading to early consolidation of the AFG and preventing collapse in five of seven hips, while the operative time and post-operative rehabilitation period were much shorter compared with free vascularised fibular grafts.

Cite this article: Bone Joint J 2014;96-B:31–5.

The June 2012 Foot & Ankle Roundup³⁶⁰ looks at: the Achilles tendon Total Rupture Score (ATRS); endoscopic treatment of Haglund’s syndrome; whether it is worth removing metalwork; hyaluronic acid injection; thromboembolic events after fracture fixation in the ankle; whether surgeons are as good as CT scans for OCD of the talus; proximal fractures of the fifth metatarsal; nerve blocks for hallux valgus surgery; chronic osteomyelitis in the non-diabetic patient; Charcot arthropathy.

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.

Objectives

Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

The December 2013 Research Roundup³⁶⁰ looks at: Inflammation implicated in FAI; Ponseti and effective teaching; Unicompartmental knee design and tibial strain; Bisphosphonates and fracture healing; Antibiosis in cement; Zoledronic acid improves primary stability in revision?; Osteoporotic fractures revisited; and electroarthrography for monitoring of cartilage degeneration

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (sd 20)), compared with metformin 10 µg/ml (185% (sd 10)), metoprolol 0.25 µg/ml (190% (sd 20)), citalopram 0.05 µg/ml (150% (sd 10)) and omeprazole 0.001 µg/ml (145% (sd 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (sd 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis.

Cite this article: Bone Joint J 2013;95-B:1575–80.

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly.

There is no absolute method of evaluating healing of a fracture of the tibial shaft. In this study we sought to validate a new clinical method based on the systematic observation of gait, first by assessing the degree of agreement between three independent observers regarding the gait score for a given patient, and secondly by determining how such a score might predict healing of a fracture.

We used a method of evaluating gait to assess 33 patients (29 men and four women, with a mean age of 29 years (15 to 62)) who had sustained an isolated fracture of the tibial shaft and had been treated with a locked intramedullary nail. There were 15 closed and 18 open fractures (three Gustilo and Anderson grade I, seven grade II, seven grade IIIA and one grade IIIB). Assessment was carried out three and six months post-operatively using videos taken with a digital camera. Gait was graded on a scale ranging from 1 (extreme difficulty) to 4 (normal gait). Bivariate analysis included analysis of variance to determine whether the gait score statistically correlated with previously validated and standardised scores of clinical status and radiological evidence of union.

An association was found between the pattern of gait and all the other variables. Improvement in gait was associated with the absence of pain on weight-bearing, reduced tenderness over the fracture, a higher Radiographic Union Scale in Tibial Fractures score, and improved functional status, measured using the Brazilian version of the Short Musculoskeletal Function Assessment questionnaire (all p < 0.001). Although further study is needed, the analysis of gait in this way may prove to be a useful clinical tool.