Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty: A randomized,double-blind,placebo-controlled trial with 116 patients

Background and purpose — The local infiltration analgesia (LIA) technique has been widely used to reduce opioid requirements and to improve postoperative mobilization following total hip arthroplasty (THA). However, the evidence for the efficacy of LIA in THA is not yet clear. We determined whether single-shot LIA in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA.Patients and methods — 116 patients undergoing primary THA under spinal anesthesia were included in this randomized, double-blind, placebo-controlled trial. All patients received oral opioid-sparing multimodal analgesia: etoricoxib, acetaminophen, and glucocorticoid. The patients were randomized to receive either 150 mL ropivacaine (2 mg/mL) and 0.5 mL epinephrine (1 mg/mL) or 150 mL 0.9% saline. Rescue analgesic consisted of morphine and oxycodone as needed. The primary endpoint was pain during mobilization in the recovery unit. Secondary endpoints were pain during mobilization on the day after surgery and total postoperative opioid requirements on the first postoperative day.Results — The levels of pain during mobilization—both in the recovery unit and on the day after surgery—and consumption of opioids on the first postoperative day were similar in the 2 groups.Interpretation — LIA did not provide any extra analgesic effect after THA over and above that from the multimodal analgesic regimen used in this study.Implementation of accelerated clinical pathways based on the fast-track principles reduces morbidity and enhances recovery for patients undergoing THA (Kehlet and Wilmore 2008). One of the key prerequisites is optimized pain relief, allowing early postoperative mobilization (Kehlet and Wilmore 2008). This requires that the pain treatment should be safe and effective, both at rest and during activity (Srikandarajah and Gilron 2011).The concept of multimodal analgesia for acute postoperative pain is to combine analgesics with additive or synergistic effects, which is meant to reduce the use of—and the adverse effects of—opioids and to allow early mobilization (Kehlet and Dahl 1993, Kehlet et al. 1999, Buvanendran and Kroin 2009). Multimodal analgesia in THA usually includes analgesics such as opioids, gabapentin, NSAIDs, acetaminophen, glucocorticoids, and local infiltration (Kardash et al. 2008, Kerr and Kohan 2008, Toms et al. 2008, Fredheim et al. 2011, Maund et al. 2011, Zhang et al. 2011).Kerr and Kohan (2008) reported reduced opioid requirements and reduced hospital stay with the use of LIA consisting of ropivacaine and NSAIDs. However, trials investigating the effect of ropivacaine in LIA have not determined whether ropivacaine alone gives similar improvements following THA (Lunn et al. 2011, Dobie et al. 2012, Zoric et al. 2014). Studies using LIA have often combined different analgesics (Kerr and Kohan 2008, Kuchalik et al. 2013), and this complicates interpretation of the results regarding the extent to which ropivacaine alone contributes to the outcome.Various studies have shown that LIA does not provide any additional analgesic benefit or reduce opioid consumption after THA (Lunn et al. 2011, Dobie et al. 2012, Solovyova et al. 2013, Zoric et al. 2014), and some authors do not recommend LIA in addition to a multimodal analgesic regimen after THA (Andersen et al. 2011, Lunn et al. 2011). Other studies have shown that LIA reduces the opioid consumption (Andersen et al. 2007, Kerr and Kohan 2008, Busch et al. 2010, Murphy et al. 2012, Kuchalik et al. 2013) and shortens the hospital stay after THA (Kerr and Kohan 2008, Scott et al. 2012) The results are thus conflicting, and the role of LIA in THA surgery still needs to be clarified.We investigated whether a single-shot LIA with ropivacaine in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA.     

Moderate varus/valgus malalignment after total knee arthroplasty has little effect on knee function or muscle strength: 91 patients assessed after 1 year

Background and purpose — Postoperative muscle strength and component alignment are important factors affecting functional results after total knee arthroplasty (TKA). We are not aware of any studies that have investigated the relationship between them. We therefore investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.Patients and methods — We included 120 consecutive osteoarthritis (OA) patients admitted for TKA. Preoperative active range of motion (ROM) of the knee, patient age, sex, and BMI were recorded and the Knee Society score (KSS) and knee joint extensor/flexor muscle strength were assessed. At 1-year follow-up, the mechanical and coronal component alignment was measured from a postoperative long standing radiograph, and ROM, KSS, and muscle strength measurements were taken in 91 patients. Functional outcome and muscle strength measurements were compared between normally aligned and malaligned TKA groups.Results — 29 of 91 TKAs were malaligned, i.e. they deviated more than 3° from the neutral mechanical axis. 18 femoral components and 15 tibial components were malaligned. Before surgery, the malaligned and normally aligned groups were similar regarding sex distribution, BMI, ROM, KSS, and muscle strength. At the 1-year follow-up, the differences between the groups regarding knee joint function and muscle strength were small, not statistically significant, and barely clinically relevant.Interpretation — Moderate varus/valgus malalignment of the mechanical axis or of individual components has no relevant clinical effect on function or muscle strength 1 year after TKA surgery.Failure to restore limb alignment in total knee arthroplasty (TKA) increases the risk of revision (Jeffery et al. 1991, Ritter et al. 1994 and 2011, Berend et al. 2004), but the effect of accurate postoperative alignment on TKA function is controversial (Lotke and Ecker 1977, Choong et al. 2009, Fang et al. 2009, Longstaff et al. 2009, Huang et al. 2012).Huang et al. (2012) reported that TKAs with a coronal alignment within 3° from the neutral axis had better function and quality of life at 5-year follow-up than TKAs that deviated more than 3° from neutral alignment. Other studies comparing computer-assisted TKA with conventional TKA surgery have not been able to correlate malalignment with inferior functional outcomes (Spencer et al. 2007, Kamat et al. 2009, Kim et al. 2009, Burnett and Barrack 2013).Patients with greater preoperative muscle strength have been reported to have faster recovery and better functional outcome after TKA (Mizner et al. 2005, Yoshida et al. 2008). However, full recovery of muscle strength after TKA is uncommon (Berth et al. 2002, Valtonen et al. 2009, Maffiuletti et al. 2010, Vahtrik et al. 2012).It is plausible that failure to restore the mechanical axis restoration results in inferior muscle function. Sogabe et al. (2009) found different cross-sectional areas in the quadriceps muscles with different knee alignments. They suggested that knees with varus or valgus deformation should have poorer muscle function compared to normally aligned knees. However, we have not been able find any studies investigating muscle strength after TKA in relation to component alignment and mechanical axis restoration.We investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.     

Muscular strength after total hip arthroplasty: A prospective comparison of 3 surgical approaches

ResultsDifferences in maximal strength change were greatest after 2 and 8 days. The posterior and anterior approaches produced less decrease in muscular strength than the direct lateral approach. 6 weeks postoperatively, the posterior approach produced greater increase in muscular strength than the direct lateral approach, and resulted in a greater increase in abduction strength than the anterior approach. At 3-month follow-up, no statistically significant differences between the groups were found. The operated legs were 18% weaker in leg press and 15% weaker in abduction than the unoperated legs, and the results were similar between groups.InterpretationThe posterior and anterior approaches appeared to have the least negative effect on abduction and leg press muscular strength in the first postoperative week; the posterior approach had the least negative effect, even up to 6 weeks postoperatively. THA patients have reduced muscle strength in the operated leg (compared to the unoperated leg) 3 months after surgery.Regaining muscular strength is important for postoperative function after hip arthroplasty. Inactivity reduces muscular strength and physical function (McGuire et al. 2001, Suesada et al. 2007, Kortebein et al. 2008), and muscular strength decreases substantially in the first week after total hip arthroplasty (THA) (Holm et al. 2013). Early recovery and rehabilitation of the weakened musculature is therefore of importance (Sicard-Rosenbaum et al. 2002). The type of surgical approach used has a major impact on THA stability and muscle function (Masonis and Bourne 2002).The direct lateral approach (DLA) is associated with a low dislocation risk (Witzleb et al. 2009), but of concern is that it traumatizes the abductor muscles, which can lead to permanent postoperative limp and weakness (Edmunds and Boscainos 2011). The posterior approach (PA) has been associated with postoperative dislocations (Edmunds and Boscainos 2011, Brooks 2013), mainly owing to the small femoral heads used to prevent wear (Bystrom et al. 2003). However, the introduction of highly cross-linked polyethylene into the articulation has reduced wear independently of head diameter (Bragdon et al. 2007), leading to increased use of larger head diameters (Lombardi et al. 2011). It has also been shown that a posterior soft-tissue repair following PA reduces the dislocation rate (van Stralen et al. 2003, Suh et al. 2004). The anterior approach (AA), first described by Robert Judet in 1947 as a modified Smith-Petersen approach, follows the principles of minimally invasive surgery. This approach provides intermuscular and internervous exposure to the hip (Wojciechowski et al. 2007), leading to reduced soft-tissue dissection and trauma (Bergin et al. 2011). Concerns have been related to higher complication rates owing to wound complications, intraoperative fracture, and compromised fixation after minimally invasive surgery, with increased risks of early revision surgery (Graw et al. 2010).There is no consensus on the relative functional advantages of different surgical approaches (Gulati et al. 2008, Edmunds and Boscainos 2011), and differences in maximal strength have not been examined. To our knowledge, there have been no studies comparing the DLA, the PA, and the AA in terms of early maximal muscular strength. We compared these 3 surgical approaches with regard to regaining of maximal muscular strength by 3 months postoperatively in patients undergoing THA.     

Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

ResultsIn Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 10⁵ person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 10⁵ person-years in 1997 to 97 per 10⁵ person-years in 2012, but not in Sweden.InterpretationThe incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries.Degenerative knee disease produces a variety of symptoms, clinical findings, and tissue abnormalities, eventually leading to knee osteoarthritis (OA). Nonoperative treatment of degenerative knee disease is recommended in guidelines, but arthroscopy is widely used (Kim et al. 2011, Nelson et al. 2014). Arthroscopic treatment includes debridement (lavage, smoothening, and removal of loose articular cartilage fragments), treatment of cartilage lesions, and resection of meniscal lesions (Felson 2010). Meniscal repair is preferred for acute traumatic tears of the meniscus (Sgaglione 2005). However, it is often difficult to distinguish between degenerative and traumatic meniscal tears. In older individuals and in patients with knee OA, meniscal tears are often degenerative and their prevalence increases with age (Curl et al. 1997, Metcalf and Barrett 2004, Englund et al. 2008). In younger patients, traumatic meniscal tears usually result from acute knee injury and are often associated with tears of the anterior cruciate ligament (Poehling et al. 1990).The practice of knee arthroscopy is in turmoil. In 2002, a pivotal randomized and placebo- (surgery) controlled trial found that arthroscopic debridement or lavage is no better than a sham procedure for treating knee OA (Moseley et al. 2002). This finding was later corroborated by Kirkley et al. (2008). This evidence led to recommendations to avoid knee arthroscopy procedures for patients with a primary diagnosis of knee OA (Conaghan et al. 2008, Richmond et al. 2009, Zhang et al. 2010). The recommendations, however, provided the option of knee arthroscopy in patients with signs and symptoms of a torn meniscus (Conaghan et al. 2008, Richmond et al. 2009) and for patients with low-grade OA (Zhang et al. 2010).Previous reports regarding the trends in a number of knee arthroscopic procedures indicate a reduced incidence of arthroscopies for knee OA, and a steady increase in the number of arthroscopic meniscus surgeries (Hawker et al. 2008, Kim et al. 2011, Abrams et al. 2013). In the UK, the incidence of arthroscopic meniscal resections more than doubled from 2000 to 2012 in patients over 60 years of age (Lazic et al. 2014). Similarly, in Denmark the number of meniscal procedures in patients aged 35 years or more increased during the period 2000–2011 (Thorlund et al. 2014).In this bi-national registry-based study involving the entire populations of Finland and Sweden, we assessed the numbers and incidence trends of arthroscopic knee procedures for degenerative knee disease and meniscal tears in Finland (between 1997 and 2012) and in Sweden (between 2001 and 2012).     

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model

Background and purpose — Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984).Methods — ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry.Results — Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%).Interpretation — This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs.Male and female hormones, which act mainly via androgen receptors (ARs) and estrogen receptors (ERs), are physiological regulators of bone remodeling (Clarke and Khosla 2009, Vanderschueren et al. 2014). Drug development programs have successfully launched non-steroidal selective estrogen receptor modulators (SERMs) for various clinical indications, including postmenopausal osteoporosis (Komm and Mirkin 2014). The common goal of the corresponding programs for non-steroidal tissue-selective androgen receptor modulators (SARMs), which act as AR ligands, is to achieve systemic anabolic effects on bones and muscles without adverse androgenic effects (Mohler et al. 2009). Preclinical models have shown that the systemic administration of SARMs can protect the skeleton from the catabolic effects of orchiectomy and ovariectomy (Gao et al. 2005, Kearbey et al. 2007), partially restore the bone mass lost by ovariectomy (Kearbey et al. 2009), and enhance the therapeutic effects of anti-resorptive drug treatment (Vajda et al. 2009). The main clinical target of SARMs is aging populations with sarcopenia and bone frailty (Mohler et al. 2009), but no SARMs have yet reached the market.ARs are highly expressed in mature osteoblasts and osteocytes (Abu et al. 1997, Wiren et al. 2002), and androgens have been traditionally claimed to have direct anabolic bone effects. Data from studies on androgen-insensitive null mice with non-functional ARs (Yeh et al. 2002, Kawano et al. 2003, Venken et al. 2006, Sinnesael et al. 2012) and in mice that overexpress ARs (Wiren et al. 2004, 2008) have confirmed the physiological significance of AR-mediated bone remodeling processes. The androgenic action may be partly compartment-specific, and anabolic effects mainly appear at periosteal surfaces (Wiren et al. 2004, 2008, 2010, 2011), but several studies have clearly demonstrated that the lack of AR action results in general trabecular bone loss (Vanderschueren et al. 2014).Clinically, there are unmet needs for bone enhancement agents in elective reconstructive procedures and also in trauma surgery. One unexplored therapeutic option would be local application of SARMs as an anabolic bone agent. In this pilot study, the osteogenic efficacy of a SARM compound (ORM-11984) was tested in a rat bone marrow ablation model. Bone marrow ablation is a unique bone-healing model in which robust endosteal intramembranous bone formation is induced transiently by surgical ablation of the bone marrow (Suva et al. 1993). ARs are present in mesenchymal stromal stem cells of the bone marrow (Bellido et al. 1995), which are among the repair cells responsible for bone-healing processes (Bais et al. 2009). We hypothesized that the intramedullary administration of ORM-11984 would have androgenic anabolic effects on bone marrow-derived precursor cells and produce a dose-dependent enhancement of the local osteogenic response.     

Which patients do not recover from shoulder impingement syndrome,either with operative treatment or with nonoperative treatment?: Subgroup analysis involving 140 patients at 2 and 5 years in a randomized study

Background and purpose — Shoulder impingement syndrome is common, but treatment is controversial. Arthroscopic acromioplasty is popular even though its efficacy is unknown. In this study, we analyzed stage-II shoulder impingement patients in subgroups to identify those who would benefit from the operation.Patients and methods — In a previous randomized study, 140 patients were either treated with a supervised exercise program or with arthroscopic acromioplasty followed by a similar exercise program. The patients were followed up at 2 and 5 years after randomization. Self-reported pain was used as the primary outcome measure.Results — Both treatment groups had less pain at 2 and 5 years, and this was similar in both groups. Duration of symptoms, marital status (single), long periods of sick leave, and lack of professional education appeared to increase the risk of persistent pain despite the treatment. Patients with impingement with radiological acromioclavicular (AC) joint degeneration also had more pain. The patients in the exercise group who later wanted operative treatment and had it did not get better after the operation.Interpretation — The natural course probably plays a substantial role in the outcome. Based on our findings, it is difficult to recommend arthroscopic acromioplasty for any specific subgroup. Regarding operative treatment, however, a concomitant AC joint resection might be recommended if there are signs of AC joint degeneration. Even more challenging for the development of a treatment algorithm is the finding that patients who do not recover after nonoperative treatment should not be operated either.Shoulder impingement syndrome has traditionally been divided into 3 progressive stages: (1) edema and hemorrhage (stage I), (2) fibrosis and tendinitis (stage II), and (3) tears of the rotator cuff, biceps ruptures, and bone changes (stage III) (Neer 1983). Nowadays, the term impingement syndrome is used to refer to a full range of rotator cuff abnormalities, being still a diagnosis based on physical examination (Papadonikolakis et al. 2011). Diercks et al. (2014) highlighted the need for a combination of clinical tests in the diagnosis, and suggested the use of an imaging test after prolonged symptoms (of more than 6 weeks) to rule out rotator cuff tears. Shoulder impingement is a common cause of shoulder pain (van der Windt et al. 1995, Urwin et al. 1998). Tendinopathy is considered to have a multifarious etiology: intrinsic mechanisms may be more important than extrinsic mechanisms (Factor and Dale 2014).Both nonoperative treatment and operative treatment have been used to treat this syndrome (Coghlan et al. 2008, Dorrestijn et al. 2009, Kromer et al. 2009, Chaudhury et al. 2010). It has been shown that arthroscopic acromioplasty is not superior to a supervised exercise program (Ketola et al. 2009, 2013, Papadonikolakis et al. 2011, Diercks et al. 2014, Saltychev et al. 2015). However, arthroscopic acromioplasty has been increasingly used during the last decade (Paloneva et al. 2015). Similar results have been obtained with open and arthroscopic acromioplasty (Davis et al. 2010). It is unclear whether a specific subgroup of patients who would benefit from arthroscopic acromioplasty can be identified. In most studies, the inclusion criterion has simply been failure of nonoperative treatment (Brox et al. 1999, Henkus et al. 2009). We have already done a cost-effectiveness study that suggested that arthroscopic acromioplasty followed by a structural exercise program is less cost-effective than exercise treatment alone (Ketola et al. 2009), and this was confirmed by Saltychev et al. (2015). We have now analyzed the 140 impingement patients from our previous study (Ketola et al. 2009) in subgroups to find out whether there is a subgroup of patients who would really benefit from arthroscopic acromioplasty. Secondly, we wanted to determine whether there is a subgroup in which the procedure should be avoided.     

The role of “cell therapy” in osteonecrosis of the femoral head: A systematic review of the literature and meta-analysis of 7 studies

ResultsThe pooled estimate of effect size for structural failure of the femoral head favored the cell therapy group, as, in this treatment group, the odds of progression of the femoral head to the collapse stage were reduced by a factor of 5 compared to the CD group (odds ratio (OR) = 0.2, 95% CI: 0.08–0.6; p = 0.02). The respective summarized estimate of effect size yielded halved odds for conversion to THR in the cell therapy group compared to CD group (OR = 0.6, 95% CI: 0.3–1.02; p = 0.06).InterpretationOur findings suggest that implantation of autologous mesenchymal stem cells (MSCs) into the core decompression track, particularly when employed at early (pre-collapse) stages of ONFH, would improve the survivorship of femoral heads and reduce the need for hip arthroplasty.Osteonecrosis of the femoral head (ONFH) is a progressive disease caused by a critical reduction in the blood supply to the femoral head and elevation of intraosseous pressure. Although its pathogenesis is poorly understood, it is generally accepted that various traumatic and non-traumatic insults compromise the already precarious circulation of the femoral head, leading to bone marrow and osteocyte death—and eventually collapse of the necrotic segment (Mont and Hungerford 1995). It mostly affects young adults, causing considerable morbidity (Slobogean et al. 2015). The annual incidence of ONFH in the USA is estimated to be 15,000–20,000 cases (Vail and Covington 1997). Most cases without any treatment progress to femoral head collapse and joint destruction, with total hip arthroplasty being the only treatment option (Lieberman et al., 2003). Magnetic resonance imaging (MRI) has contributed to early (pre-collapse) detection of the disease, providing an opportunity for timely intervention in order to avoid femoral head collapse and subsequent joint destruction.Various nonoperative and operative treatment modalities have been used to prevent—or at least delay—the progress of the disease towards femoral head collapse. Core decompression is a commonly used procedure, particularly in pre-collapse stages, but its effectiveness remains controversial (Ficat 1985, Learmonth et al. 1990, Markel et al. 1996, Saito et al. 1988, Yoon et al. 2001). Current research has focused on clarifying the molecular mechanisms involved in the pathogenesis of ONFH (Gangji and Hauzeur 2009, Kasten et al. 2008, Lee et al. 2009). Particular attention has been paid to multipotent mesenchymal stem cells (MSCs) and their ability to maintain mitotic multiplication while being capable of differentiating into various cellular types, such as osteoblasts, osteocytes, chondrocytes, and adipocytes (Baksh et al. 2004). Experimentally, MSCs have been shown to enhance tissue regeneration when transplanted in areas of necrotic bone (Yan et al. 2009). Various researchers have pioneered the clinical application of cell-based methods for the treatment of ONFH (Hernigou and Beaujean 2002, Gangji and Hauzeur 2005, Calori et al. 2014). Their technique was used in conjunction with the classical core decompression procedure and involved harvesting of autologous bone marrow aspirate, isolation of its mononuclear cell fraction, and injection of it into the necrotic zone of the femoral head through the canal of the preceding core decompression. This treatment strategy was based on the hypothesis that multiipotent MSCs in the bone marrow aspirate could repopulate the trabeculae of the necrotic zone within the femoral head, enhancing regeneration and remodeling of the necrotic bone (Hernigou et al. 2004).We performed a meta-analysis to investigate whether implantation of autologous bone marrow aspirate, containing MSCs, into the core decompression track would improve the clinical and radiological results of ONFH compared to the classical method of core decompression alone. The primary outcomes of interest were structural failure (collapse) of the femoral head and conversion to total hip replacement (THR).     

Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases

Background and purpose — Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment.Patients and methods — We retrospectively reviewed all 4 cases (aged 38–77 years) of transtibial amputations managed with osseointegration and TKR in 2012–2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1–3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test.Results — There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29–52 and a 6-minute walk test improvement range of 37–84 meters.Interpretation — It is possible to combine TKR with osseointegrated implants.Socket-related discomfort leads to a significant reduction in the quality of life of individuals with lower limb amputation (Dillingham et al. 2001, Gholizadeh et al. 2014). Socket-skin interface problems lead to poor fit, diminished proprioception in the amputated limb, lack of rotational control, and reduction of ipsilateral proximal joint movement (Legro et al. 1999, Lyon et al. 2000, Meulenbelt et al. 2006).A direct connection of the prosthetic limb to the bone using osseointegrated implants can address these socket-related problems (Van de Meent et al. 2013, Tsikandylakis et al. 2014). Brånemark introduced this surgical procedure in 1995. He adapted osseointegration principles established in dental surgery to the rehabilitation of individuals with transfemoral amputation using a percutaneous bone anchoring implant screwed into the femur (Brånemark et al. 2001). Hip replacement spongiosa surface coating technology has been used to make a chrome cobalt intramedullary press-fit implant (Endo-Exo Prosthesis) allowing larger surface area for osseointegration and faster rehabilitation (Staubach and Grundei 2001). Al Muderis et al. (2015) adapted highly porous plasma-sprayed titanium implants to provide optimum initial press-fit and solid bone ingrowth.Studies of transfemoral implants have found improved quality of life, prosthetic use, body image, hip range of motion, sitting comfort, and walking ability (Van de Meent et al. 2013, Hagberg et al. 2014). For example, substantial improvements in health-related quality of life using the Global component of the questionnaire for transfemoral amputees (Q-TFA)—of 38 points (Hagberg et al. 2014) and 24 points (Van de Meent et al. 2013)—have been reported in 2 case series of 51 and 22 patients, respectively.Similar benefits could be expected for transtibial amputees using osseointegrated implants, as the knee joint could possibly enhance their gait. A study of 39 cases involving upper and lower limb prostheses (Tillander et al. 2010) found infections in 7 patients at an average follow-up period of 54 (3–132) months, with no infections reported for 1 tibial implant. At our own center, preliminary evidence of the safety and effectiveness of the tibial impants in 22 transtibial amputees with a minimum of 6 months of follow-up gave results consistent with the published results for transfemoral amputations (Khemka et al. 2015).Few authors have reported on the safety of this procedure (Brånemark et al. 2014, Tsikandylakis et al. 2014). One of the largest studies included 51 patients and reported superficial infections in approximately half of these patients at 2-year follow-up. In that study, the implant was removed in 1 patient due to deep infection and in 3 patients due to aseptic loosening (Brånemark et al. 2014).Osseointegrated implants are not currently recommended for transtibial amputees with ultra-short residuum. In addition to the practical technical challenges, biomechanical studies have suggested that small bone-implant contact is more likely to increase the risk of loosening (Lohr et al. 2000, Henriksen et al. 2003, Carvalho et al. 2012). Osseointegration is also not currently recommended for those suffering from ipsilateral knee osteoarthritis because it is hypothesized that an osseointegrated tibial implant will aggravate arthritic symptoms due to mechanical forces (Frossard et al. 2008).We describe the surgical procedure and early results of combining a total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment for the first time.     

Better survival of hybrid total knee arthroplasty compared to cemented arthroplasty: A report from the Norwegian Arthroplasty Register 1999–2012

Background and purpose — There have been few comparative studies on total knee replacement (TKR) with cemented tibia and uncemented femur (hybrid TKR). Previous studies have not shown any difference in revision rate between cemented and hybrid fixation, but these studies had few hybrid prostheses. We have evaluated the outcome of hybrid TKR based on data from the Norwegian Arthroplasty Register (NAR).Patients and methods — We compared 4,585 hybrid TKRs to 20,095 cemented TKRs with risk of revision for any cause as the primary endpoint. We included primary TKRs without patella resurfacing that were reported to the NAR during the years 1999–2012. To minimize the possible confounding effect of prosthesis brands, only brands that were used both as hybrids and cemented in more than 200 cases were included. Kaplan-Meier survival analysis and Cox regression analysis were done with adjustment for age, sex, and preoperative diagnosis. To include death as a competing risk, cumulative incidence function estimates were calculated.Results — Estimated survival at 11 years was 94.3% (95% CI: 93.9–94.7) in the cemented TKR group and 96.3% (CI: 95.3–97.3) in the hybrid TKR group. The adjusted Cox regression analysis showed a lower risk of revision in the hybrid group (relative risk = 0.58, CI: 0.48–0.72, p < 0.001). The hybrid group included 3 brands of prostheses: LCS classic, LCS complete, and Profix. Profix hybrid TKR had lower risk of revision than cemented TKR, but the LCS classic and LCS complete did not. Kaplan-Meier estimated survival at 11 years was 96.8% (CI: 95.6–98.0) in the hybrid Profix group and 95.2% (CI: 94.6–95.8) in the cemented Profix group. Mean operating time was 17 min longer in the cemented group.Interpretation — Survivorship of the hybrid TKR at 11 years was better than that for cemented TKR, or the same, depending on the brand of prosthesis. Hybrid fixation appears to be a safe and time-efficient alternative to cemented fixation in total knee replacement surgery.Total knee joint replacement (TKR) is a highly successful operation with survival rates of more than 90% at 10 years (Carr et al. 2012). Only a few large comparative studies on different designs have been published (Knutson et al. 1986, Rand and Ilstrup 1991, Knutson et al. 1994, Robertsson 2000, Furnes et al. 2002, 2007, Sibanda et al. 2008). Most previous studies were not conclusive, due to their being too small or being biased with potential conflicts of interests (Carr et al. 2012). In the only meta-analysis on this topic, Nakama et al. (2012) found only 3 small randomized controlled studies that could be included for quantitative analysis. These authors were not able to make any conclusions about whether the prostheses should be cement-fixated, cementless, or hybrid.The fixation of primary TKRs has been extensively discussed, but no general agreement has been reached (Nakama et al. 2012). Cemented prostheses are regarded as the gold standard for TKR, supported by the long-term clinical success and survivorship analysis from registry-based and clinical studies (Robertsson 2000, Bellemans et al. 2005, Nakama et al. 2012). Cementless fixation is, however, still of interest to clinicians, who have used it in an attempt to reduce operation time, improve prosthetic durability, and preserve bone stock (Bassett 1998, Duffy et al. 1998, Nelissen et al. 1998, Regner 1998, Abu-Rajab et al. 2006).There have been few studies comparing the survival of different prosthesis brands and implant designs. A previous study from the Norwegian Arthroplasty Register (NAR) did not find any significant short-term differences at 5 years between the most commonly used brands in Norway (Furnes et al. 2002). The study did not show any significant differences in the overall revision rates between different fixation methods, but the number of hybrid prostheses was low, with only 739 knees (10%). The median follow-up time was short, number of prosthesis brands was high (7), and the power of the study was low regarding fixation method, due to low numbers of hybrid and cementless prostheses.In Sweden, almost all TKRs are cemented (SKAR, 2012). In Australia, there is more variation in fixation; more than 20% of TKRs have hybrid fixation (AOA 2012). In the report from 2011, for the first time hybrid fixation performed better than both cemented and cementless fixation at 10 years. Annual cumulative percent revision of primary TKR at 10 years was 5.6% (5.3–6.0) with cement fixation and 5.0 (4.6–5.3) with hybrid fixation (p = 0.02) (AOA 2012).There have been very few randomized prospective studies comparing primary TKRs using cemented fixation and primary TKRs using hydroxyapatite-coated, hybrid fixation. Most of them have compared uncemented fixation of the tibia and cemented fixation of the tibia. These studies have shown similar or inferior results for uncemented fixation (Nilsson et al. 1999, Regner et al. 2000, Carlsson et al. 2005, Beauprè et al. 2007). Short-term studies of hybrid fixation with cemented femur showed promising results (Faris et al. 2008). However, 1 medium-term report of 65 press-fit condylar arthroplasties had unacceptable implant survivorship and problems with the femoral component (Campbell et al. 1998).We compared the failure rates and mechanisms of failure of primary hybrid TKRs with those of primary cemented TKRs using the nationwide prospective observational register of knee implants in Norway.     

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy: A 15-year follow-up of 32,476 total knee arthroplasties in the Norwegian Arthroplasty Register

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material.Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis.Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8).Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty.High tibial osteotomy (HTO) is a well-established joint preserving procedure for the treatment of medial knee osteoarthritis. The goal is to achieve unloading of the affected medial compartment of the knee to prevent or postpone the need for an artificial knee joint. This is performed by slightly overcorrecting the knee joint from varus malalignment to valgus or neutral position. Osteotomy was a standard treatment option for unicompartmental knee osteoarthritis in earlier years before knee arthroplasty was a surgical option, but osteotomy lost importance in the 1980s because of the success of knee replacement surgery (Smith et al. 2013). However, there has been an increase in osteotomies during the last 15 years, especially in younger patients in some countries (Seil et al. 2013). National arthroplasty registers have demonstrated higher risk of revision for knee arthroplasty in younger patients (under the age of 60) (NAR 2014, SKAR 2013). The 2 most commonly used methods for HTO are lateral closing wedge and medial opening wedge osteotomy. Both methods have shown improvement in knee pain and function (Naudie et al. 1999, van Raaij et al. 2008, Efe et al. 2011, W-Dahl et al. 2012). Nevertheless, some patients later require a second procedure, a total knee arthroplasty (Naudie et al. 1999), depending on the degree of osteoarthritis, their level of pain and function, and the degree of correction achieved. Although total knee arthroplasty appears to be technically more challenging after HTO in cases with severe overcorrection, bone stock loss, altered joint line (Figures 1 and ​and2),2), or patella infera, only a few studies have found inferior results compared to primary TKA (Windsor et al. 1988, Parvizi et al. 2004, Haslam et al. 2007, Farfalli et al. 2012). The aim of this study was to evaluate the risk of revision after TKA, comparing primary TKA with and without previous high tibial osteotomy using data from the Norwegian Arthroplasty Register (NAR).Open in a separate windowFigure 1.Example of extra-articular malalignment after high tibial osteotomy (HTO) with opening wedge technique. The red line on the left radiograph (a) indicates the mechanical axis lateral to the knee joint. The radiograph to the right (b) indicates the extra-articular angulation of the tibia in the osteotomy area.Open in a separate windowFigure 2.Example of intra-articular malalignment after high tibial osteotomy (WTO) with closing wedge technique. The solid red line indicates that the tibial plateau has been elevated medially and is not perpendicular to the tibial axis.     

Open reduction and internal fixation aided by intraoperative 3-dimensional imaging improved the articular reduction in 72 displaced acetabular fractures

Background and purpose — During acetabular fracture surgery, the acetabular roof is difficult to visualize with 2-dimensional fluoroscopic views. We assessed whether intraoperative 3-dimensional (3D) imaging can aid the surgeon to achieve better articular reduction and improve implant fixation.Patients and methods — We operated on 72 acetabular fractures using intraoperative 3D imaging and compared the operative results, duration of surgery, and complications with those for 42 consecutive acetabular fracture operations conducted using conventional fluoroscopic imaging. Postoperative reduction was evaluated on reconstructed coronal and sagittal images of the acetabulum.Results — The fracture severity and patient characteristics were similar in the 2 groups. In the 3D group, 46 of 72 patients (0.6) had a perfect result after open reduction and internal fixation, and in the control group, 17 of 42 (0.4) had a perfect result. The mean difference in postoperative articular incongruity was 0.5 mm (95% CI: 0.4–0.7). In 29 of 72 operations, the intraoperative 3D scans led to intraoperative correction of the reduction and an improved result. The duration of surgery and infection rate were similar in the 2 groups.Interpretation — Intraoperative 3D imaging, which is not time-consuming, allowed the surgeon to correct malreductions and screw placement in 29 of 72 operations, leading to better articular reduction and more precise screw placement than in operations where conventional fluoroscopic imaging was used to control the reduction.The overall incidence of coxarthrosis after acetabular fracture is high and multifactorial. Giannoudis et al. (2005) found that patients with residual articular steps of the acetabular roof smaller than 2 mm had a 13% risk of coxarthrosis and that patients with articular steps larger than 2 mm had a 43% risk. Tannast et al. (2012) reported a 27% conversion rate to arthroplasty after acetabular surgery in 816 patients, with a close correlation to the quality of reduction postoperatively. Most surgeons use computed tomography (CT) of the acetabulum to plan their approach and strategy before fracture surgery. For intraoperative decision making and for evaluation of the reduction, 2-dimensional (2D) fluoroscopic imaging is still the standard imaging modality. Several studies have found that intraoperative fluoroscopy is unable to detect clinically significant steps and incongruences of the acetabular roof, and standard postoperative anteroposterior and oblique Judet radiographs cannot detect significant articular steps and screws protruding into the joint (Borrelli et al. 2002, Moed et al. 2003, Kendoff et al. 2008).Several image intensifiers now offer 3-dimensional (3D) imaging solutions that provide the surgeon with reconstructed intraoperative 2-dimensional (2D) images in axial, coronal, and sagittal projections at a resolution and with a quality comparable to CT. Before purchase of the 3D image intensifier, we investigated whether the operative results achieved with the 3D image intensifier were better than the operative results achieved with conventional fluoroscopic control. The primary outcome measure was postoperative articular residual step and secondary outcome measures were infection and duration of operation.     

Histology of 8 atypical femoral fractures: Remodeling but no healing

Background and purpose

The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself may provide clues.

Patients and methods

Between 2008 and 2013, we collected bone biopsies including the fracture line from 4 complete and 4 incomplete atypical femoral fractures. 7 female patients reported continuous bisphosphonate use for 10 years on average. 1 patient was a man who was not using bisphosphonates. Dual-energy X-ray absorptiometry of the hip and spine showed no osteoporosis in 6 cases. The bone biopsies were evaluated by micro-computed tomography, infrared spectroscopy, and qualitative histology.

Results

Incomplete fractures involved the whole cortical thickness and showed a continuous gap with a mean width of 180 µm. The gap contained amorphous material and was devoid of living cells. In contrast, the adjacent bone contained living cells, including active osteoclasts. The fracture surfaces sometimes consisted of woven bone, which may have formed in localized defects caused by surface fragmentation or resorption.

Interpretation

Atypical femoral fractures show signs of attempted healing at the fracture site. The narrow width of the fracture gap and its necrotic contents are compatible with the idea that micromotion prevents healing because it leads to strains within the fracture gap that preclude cell survival.Atypical femoral shaft fractures are a rare type of stress fracture. They have gained attention recently because of their increasing incidence and strong association with bisphosphonate treatment (Schilcher and Aspenberg 2009, Bauer 2012, Dell et al. 2012, Shane et al. 2013). Bisphosphonates inhibit osteoclast activity and suppress bone turnover (Russell et al. 2007). This has been suggested to increase the risk of stress fracture, because reduced remodeling causes an increase in bone mineral density and matrix homogeneity (Boskey et al. 2008), which can lead to a greater propensity for formation and propagation of cracks. A high mineral-to-matrix ratio makes the bone brittle, with increased susceptibility to microdamage. In addition, bisphosphonates appear to cause an increase in advanced glycation end-products of the extracellular bone matrix (Saito et al. 2008), deteriorating the mechanical properties further. These changes combined with the high mechanical stresses at the femoral shaft could lead to an increase in local microdamage, in turn leading to fracture (Mashiba et al. 2001).In spite of these observations it remains unclear whether the reported changes in bone composition substantially contribute to the pathophysiology of atypical femoral fractures. An alternative or additional pathophysiological mechanism might be based on a reduced ability to heal microdamage. Microdamage usually occurs in bone (Norman and Wang 1997). It is taken care of by targeted remodeling: damaged areas are specifically resorbed and replaced. When bisphosphonates reduce the ability to remodel these areas, microdamage accumulates. This can progress to the formation of larger cracks, i.e. stress fractures.We have previously described the histological picture of a bisphosphonate-associated atypical femoral fracture and found indicators suggesting impaired healing of the crack, in spite of increased remodeling of the adjacent bone (Aspenberg et al. 2010). In the current study, we wanted to verify those early findings. We also made new observations that were compatible with the idea that the mechanical environment in the fracture gap plays a key role in the pathophysiology.     

A single bisphosphonate infusion does not accelerate fracture healing in high tibial osteotomies

Background

Bisphosphonates increase the callus size and strength in animal fracture studies. In a human non-randomized pilot study of high tibial osteotomies in knee osteoarthritis, using the hemicallotasis (HCO) technique, bisphosphonates shortened the healing time by 12 days. In the present randomized study, we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing. Results from the same trial, showing improved pin fixation with zoledronate, have been published separately.

Methods

46 consecutive patients (aged 35–65 years) were operated. At 4 weeks postoperatively, the patients were randomized to an intravenous infusion of either zoledronic acid or sodium chloride. Dual-energy X-ray absorptiometry (DEXA) was performed 10 weeks postoperatively. Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing. Healing was evaluated blind, with extraction of the external fixator as the endpoint. At 1.5 years, an additional radiograph was taken and the hip-knee-ankle (HKA) angle measured to evaluate whether correction had been retained.

Results

All osteotomies healed with no difference in healing time between the groups (77 (SD 7) days). Bone mineral density and bone mineral content, as assessed with DEXA, were similar between the groups. Radiographically, both groups had retained the acquired correction at the 1.5-year follow-up.

Interpretation

In this randomized comparison, a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time. In both groups, the external fixator was extracted almost 2 weeks earlier than in previous studies. The early extraction did not cause a loss of correction in either group.Pharmaceutical substances, both anabolic and anti-catabolic, have been used to modulate fracture healing (for a review, see Aspenberg 2005). Anabolic drugs such as parathyroid hormone (PTH) or bone morphogenic protein (BMP) influence the osteoblasts, either unspecifically by increasing recruitment and proliferation, or specifically by directing the progenitor cells into the osteoblastic lineage (Schindeler et al. 2008). Anti-catabolic drugs such as bisphosphonates reduce the osteoclastic activity, and have been shown to increase the strength of a healing fracture by retaining the new-formed callus (Amanat et al. 2007).Both anabolic and anti-catabolic drugs can therefore affect fracture healing, but the efficiency and mode of action of these drugs appear to differ between open and closed fractures (Tägil et al. 2010). In open fractures and other fractures associated with delayed union like distal tibial fractures, a specific anabolic drug such as a BMP sometimes appears to be necessary (Little et al. 2005, Ristiniemi et al. 2007). In a fracture in a cell-rich, well-vascularized environment an anti-catabolic drug might be sufficient (Amanat et al. 2007). Several arguments can be put forward for both the clinician and the patient to use an anti-catabolic drug instead of an anabolic one for these fractures. Apart from being considerably more expensive, the existing anabolic drugs have to be delivered into the fracture gap directly (BMP) or injected daily during the healing time (PTH).In this study, we wanted to determine whether an anti-catabolic drug would reduce the time to healing in a well-vascularized fracture, using HCO in knee osteoarthritis as a relatively standardized and relatively frequent human model of bone healing. In a non-randomized pilot study of 24 patients operated on by HCO, 12 patients were treated with one single infusion of zoledronic acid and 12 were not. In the treatment group, the frame was removed after 78 (SD 13) days as compared to 91 (SD 13) days in the untreated group (p = 0.02) (Tägil et al. 2006). In a previous study from the same group studying the influence of smoking, the treatment time in external fixator was 96 days in non-smoking patients (W-Dahl and Toksvig-Larsen 2004).In the present randomized study, the primary outcome was clinical fracture healing, evaluated blind, and we wanted to determine whether one single infusion of zoledronic acid could reduce the time to fracture healing. As secondary outcome, we evaluated the pin fixation and found almost 100% improvement in pin fixation in the uncoated pin in diaphyseal bone (Harding et al. 2010). Furthermore, the bone mineral density and bone mineral content of the osteotomy gap were compared between groups to monitor the biological effect of the single dose. Drug safety was evaluated, as well as the subjective outcome as measured with the knee-specific KOOS questionnaire. Finally, we examined whether the surgically achieved correction was maintained, using radiographic hip-knee-ankle (HKA) angle measurement after 1.5 years.