Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

Debate has raged over whether a cruciate retaining (CR) or a posterior stabilised (PS) total knee replacement (TKR) provides a better range of movement (ROM) for patients. Various sub-sets of CR design are frequently lumped together when comparing outcomes. Additionally, multiple factors have been proven to influence the rate of manipulation under anaesthetic (MUA) following TKR. The purpose of this study was to determine whether different CR bearing insert designs provide better ROM or different MUA rates. All primary TKRs performed by two surgeons between March 2006 and March 2009 were reviewed and 2449 CR-TKRs were identified. The same CR femoral component, instrumentation, and tibial base plate were consistently used. In 1334 TKRs a CR tibial insert with 3° posterior slope and no posterior lip was used (CR-S). In 803 there was an insert with no slope and a small posterior lip (CR-L) and in 312 knees the posterior cruciate ligament (PCL) was either resected or lax and a deep-dish, anterior stabilised insert was used (CR-AS). More CR-AS inserts were used in patients with less pre-operative ROM and greater pre-operative tibiofemoral deformity and flexion contracture (p < 0.05). The mean improvement in ROM was highest for the CR-AS inserts (5.9° (-40° to 55°) vs CR-S 3.1° (-45° to 70°) vs CR-L 3.0° (-45° to 65°); p = 0.004). There was a significantly higher MUA rate with the CR-S and CR-L inserts than CR-AS (Pearson rank 6.51; p = 0.04). Despite sacrificing or not substituting for the PCL, ROM improvement was highest, and the MUA rate was lowest in TKRs with a deep-dish, anterior-stabilised insert. Substitution for the posterior cruciate ligament (PCL) in the form of a PS design may not be necessary even when the PCL is deficient.

Cite this article: Bone Joint J 2013;95-B, Supple A:129–32.

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.

Objectives

Wear debris released from bearing surfaces has been shown to provoke negative immune responses in the recipient. Excessive wear has been linked to early failure of prostheses. Analysis using coordinate measuring machines (CMMs) can provide estimates of total volumetric material loss of explanted prostheses and can help to understand device failure. The accuracy of volumetric testing has been debated, with some investigators stating that only protocols involving hundreds of thousands of measurement points are sufficient. We looked to examine this assumption and to apply the findings to the clinical arena.

Background

Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes.

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.

Objectives

Osteochondral injuries, if not treated adequately, often lead to severe osteoarthritis. Possible treatment options include refixation of the fragment or replacement therapies such as Pridie drilling, microfracture or osteochondral grafts, all of which have certain disadvantages. Only refixation of the fragment can produce a smooth and resilient joint surface. The aim of this study was the evaluation of an ultrasound-activated bioresorbable pin for the refixation of osteochondral fragments under physiological conditions.

The April 2012 Research Roundup³⁶⁰ looks at who is capable of being an arthroscopist, bupivacaine, triamcinolone and chondrotoxicity, reducing scarring in injured skeletal muscle, horny Goat Weed and the repair of osseous defects, platelet-derived growth factor and fracture healing, the importance of the reserve zone in a child’s growth plate, coping with advanced arthritis, hydroxyapatite and platelet-rich plasma for bone defects, and calcium phosphate and bone regeneration

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.

Platelet-derived growth factor (PDGF) is known to stimulate osteoblast or osteoprogenitor cell activity. We investigated the effect of locally applied PDGF from poly-d,l-lactide (PDLLA)-coated implants on fracture healing in a rat model. A closed fracture of the right tibia of four-month-old Sprague-Dawley rats (n = 40) was stabilised with implants coated with a biodegradable PDLLA versus implants coated with PDLLA and PDGF. Radiographs were taken throughout the study, and a marker of DNA activity, bromodeoxyuridine (BrdU), was injected before the rats were killed at three, seven and ten days. The radiographs showed consolidation of the callus in the PDGF-treated group compared with the control group at all three time points. In the PDGF-treated group, immunohistochemical staining of BrdU showed that the distribution of proliferating cells in all cellular events was higher after ten days compared with that at three and seven days.

These results indicate that local application of PDGF from biodegradable PDLLA-coated implants significantly accelerates fracture healing in experimental animals. Further development may help fracture healing in the clinical situation.

This review examines the future of total hip arthroplasty, aiming to avoid past mistakes

Hip simulators have been used for ten years to determine the tribological performance of large-head metal-on-metal devices using traditional test conditions. However, the hip simulator protocols were originally developed to test metal-on-polyethylene devices. We have used patient activity data to develop a more physiologically relevant test protocol for metal-on-metal devices. This includes stop/start motion, a more appropriate walking frequency, and alternating kinetic and kinematic profiles.

There has been considerable discussion about the effect of heat treatments on the wear of metal-on-metal cobalt chromium molybdenum (CoCrMo) devices. Clinical studies have shown a higher rate of wear, levels of metal ions and rates of failure for the heat-treated metal compared to the as-cast metal CoCrMo devices. However, hip simulator studies in vitro under traditional testing conditions have thus far not been able to demonstrate a difference between the wear performance of these implants.

Using a physiologically relevant test protocol, we have shown that heat treatment of metal-on-metal CoCrMo devices adversely affects their wear performance and generates significantly higher wear rates and levels of metal ions than in as-cast metal implants.

High-flexion total knee replacement (TKR) designs have been introduced to improve flexion after TKR. Although the early results of such designs were promising, recent literature has raised concerns about the incidence of early loosening of the femoral component. We compared the minimum force required to cause femoral component loosening for six high-flexion and six conventional TKR designs in a laboratory experiment.

Each TKR design was implanted in a femoral bone model and placed in a loading frame in 135° of flexion. Loosening of the femoral component was induced by moving the tibial component at a constant rate of displacement while maintaining the same angle of flexion. A stereophotogrammetric system registered the relative movement between the femoral component and the underlying bone until loosening occurred.

Compared with high-flexion designs, conventional TKR designs required a significantly higher force before loosening occurred (p < 0.001). High-flexion designs with closed box geometry required significantly higher loosening forces than high-flexion designs with open box geometry (p = 0.0478). The presence of pegs further contributed to the fixation strength of components.

We conclude that high-flexion designs have a greater risk for femoral component loosening than conventional TKR designs. We believe this is attributable to the absence of femoral load sharing between the prosthetic component and the condylar bone during flexion.

The October 2014 Wrist & Hand Roundup360 looks at: pulsed electromagnetic field of no use in acute scaphoid fractures; proximal interphalangeal joint replacement: one at a time or both at once; trapeziometacarpal arthrodesis in the young patient; Tamoxifen and Dupytren’s disease; and endoscopic or open for de Quervain’s syndrome?

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.

Objectives

An ongoing prospective study to investigate failing metal-on-metal hip prostheses was commenced at our centre in 2008. We report on the results of the analysis of the first consecutive 126 failed mated total hip prostheses from a single manufacturer.

Biofilm-associated infections in wounds or on implants are difficult to treat. Eradication of the bacteria is nearly always impossible, despite the use of specific antibiotics. The bactericidal effects of high-energy extracorporeal shock waves on Staphylococcus aureus have been reported, but the effect of low-energy shock waves on staphylococci and staphylococcal biofilms has not been investigated. In this study, biofilms grown on stainless steel washers were examined by electron microscopy. We tested ten experimental groups with Staph. aureus-coated washers and eight groups with Staph. epidermidis.

The biofilm-cultured washers were exposed to low-energy shock waves at 0.16 mJ/mm² for 500 impulses. The washers were then treated with cefuroxime, rifampicin and fosfomycin, both alone and in combination. All tests were carried out in triplicate. Viable cells were counted to determine the bactericidal effect.

The control groups of Staph. aureus and Staph. epidermidis revealed a cell count of 6 × 10⁸ colony-forming units/ml. Complete eradication was achieved using the combination of antibiotic therapy (single antibiotic in Staph. aureus, a combination in Staph. epidermidis) and shock wave application (p < 0.01).

We conclude that shock waves combined with antibiotics could be tested in an in vitro model of infection.

As many as 25% to 40% of unicompartmental knee replacement (UKR) revisions are performed for pain, a possible cause of which is proximal tibial strain. The aim of this study was to examine the effect of UKR implant design and material on cortical and cancellous proximal tibial strain in a synthetic bone model. Composite Sawbone tibiae were implanted with cemented UKR components of different designs, either all-polyethylene or metal-backed. The tibiae were subsequently loaded in 500 N increments to 2500 N, unloading between increments. Cortical surface strain was measured using a digital image correlation technique. Cancellous damage was measured using acoustic emission, an engineering technique that detects sonic waves (‘hits’) produced when damage occurs in material.

Anteromedial cortical surface strain showed significant differences between implants at 1500 N and 2500 N in the proximal 10 mm only (p < 0.001), with relative strain shielding in metal-backed implants. Acoustic emission showed significant differences in cancellous bone damage between implants at all loads (p = 0.001). All-polyethylene implants displayed 16.6 times the total number of cumulative acoustic emission hits as controls. All-polyethylene implants also displayed more hits than controls at all loads (p < 0.001), more than metal-backed implants at loads ≥ 1500 N (p < 0.001), and greater acoustic emission activity on unloading than controls (p = 0.01), reflecting a lack of implant stiffness. All-polyethylene implants were associated with a significant increase in damage at the microscopic level compared with metal-backed implants, even at low loads. All-polyethylene implants should be used with caution in patients who are likely to impose large loads across their knee joint.

Cite this article: Bone Joint J 2013;95-B:1339–47.

The April 2013 Foot & Ankle Roundup³⁶⁰ looks at: whether arthroscopic arthrodesis is advantageous; osteochondral autografts; suture button associated fractures; an ultrasound solution to Achilles tendinopathy; the safety of the tendo Achilles in men; charcot and antibiotic-coated nails; and botox and Policeman’s Heel.

Matrix metalloproteinases (MMPs), responsible for extracellular matrix remodelling and angiogenesis, might play a major role in the response of the growth plate to detrimental loads that lead to overuse injuries in young athletes. In order to test this hypothesis, human growth plate chondrocytes were subjected to mechanical forces equal to either physiological loads, near detrimental or detrimental loads for two hours. In addition, these cells were exposed to physiological loads for up to 24 hours. Changes in the expression of MMPs -2, -3 and -13 were investigated.

We found that expression of MMPs in cultured human growth plate chondrocytes increases in a linear manner with increased duration and intensity of loading. We also showed for the first time that physiological loads have the same effect on growth plate chondrocytes over a long period of time as detrimental loads applied for a short period.

These findings confirm the involvement of MMPs in overuse injuries in children. We suggest that training programmes for immature athletes should be reconsidered in order to avoid detrimental stresses and over-expression of MMPs in the growth plate, and especially to avoid physiological loads becoming detrimental.

Cite this article: Bone Joint J 2013;95-B:568–73.