Lars Nordsletten

Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture

BACKGROUND Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P=0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254 [ClinicalTrials.gov].).

Epidemiology of hip fractures in Oslo, Norway

The incidence of hip fractures in Oslo has shown a secular increase during the past decades. The main aims of the present study were to report the current incidence of hip fractures in Oslo and to determine whether there is a seasonal variation in the occurrence of fractures. Using the electronic diagnosis registers and the lists of the operating theater for the hospitals in Oslo with somatic care, all patients with ICD-9 code 820.X (hip fracture) from May 1, 1996 to April 30, 1997 were identified. Medical records for all identified patients were obtained and diagnosis was verified. Using the population of Oslo on January 1, 1997 as the population at risk, the age- and gender-specific annual incidence rates were calculated. These rates were compared with those for 1988/89 and 1978/79. Outdoor temperature data for Oslo were obtained to study the relation between temperature and number of hip fractures. A total number of 1316 hip fractures was included, of which 78% occurred in women. An exponential increase in incidence with age was observed in both genders. The age-adjusted fracture rates per 10,000 for the age group > or =50 years were 118.0 and 44.0 in 1996/97, 124.3 and 44.9 in 1988/89, and 104.5 and 35.8 in 1978/79 for women and men, respectively. There was no significant seasonal variation in the incidence of hip fractures and no correlation between mean outdoor temperature and number of fractures for each month in 1996/97. The data show that the incidence of hip fractures in Oslo has not changed significantly during the last decade, and it is still the highest reported. The cold climate of Oslo does not seem to contribute to the high incidence.

Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.

BACKGROUND The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to improve the healing of open tibial shaft fractures has been the focus of two prospective clinical studies. The objective of the current study was to perform a subgroup analysis of the combined data from these studies. METHODS Two prospective, randomized clinical studies were conducted. A total of 510 patients with open tibial fractures were randomized to receive the control treatment (intramedullary nail fixation and routine soft-tissue management) or the control treatment and an absorbable collagen sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2 implant was placed over the fracture at the time of definitive wound closure. For the purpose of this analysis, only the control treatment and the Food and Drug Administration-approved concentration of rhBMP-2 (1.50 mg/mL) were compared. Patients who anticipated receiving planned bone-grafting as part of a staged treatment were excluded from enrollment. RESULTS Fifty-nine trauma centers in twelve countries participated, and patients were followed for twelve months postoperatively. Two subgroups were analyzed: (1) the 131 patients with a Gustilo-Anderson type-IIIA or IIIB open tibial fracture and (2) the 113 patients treated with reamed intramedullary nailing. The first subgroup demonstrated significant improvements in the rhBMP-2 group, with fewer bone-grafting procedures (p = 0.0005), fewer patients requiring invasive secondary interventions (p = 0.0065), and a lower rate of infection (p = 0.0234), compared with the control group. The second subgroup analysis of fractures treated with reamed intramedullary nailing demonstrated no significant difference between the control and the rhBMP-2 groups. CONCLUSIONS The addition of rhBMP-2 to the treatment of type-III open tibial fractures can significantly reduce the frequency of bone-grafting procedures and other secondary interventions. This analysis establishes the clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge implant for the treatment of these severe fractures.

Hemiarthroplasty or internal fixation for intracapsular displaced femoral neck fractures: randomised controlled trial

Objective To compare the functional results after displaced fractures of the femoral neck treated with internal fixation or hemiarthroplasty. Design Randomised trial with blinding of assessments of functional results. Setting University hospital. Participants 222 patients; 165 (74%) women, mean age 83 years. Inclusion criteria were age above 60, ability to walk before the fracture, and no major hip pathology, regardless of cognitive function. Interventions Closed reduction and two parallel screws (112 patients) and bipolar cemented hemiarthroplasty (110 patients). Follow-up at 4, 12, and 24 months. Main outcome measures Hip function (Harris hip score), health related quality of life (Eq-5d), activities of daily living (Barthel index). In all cases high scores indicate better function. Results Mean Harris hip score in the hemiarthroplasty group was 8.2 points higher (95% confidence interval 2.8 to 13.5 points, P=0.003) at four months and 6.7 points (1.5 to 11.9 points, P=0.01) higher at 12 months. Mean Eq-5d index score at 24 months was 0.13 higher in the hemiarthroplasty group (0.01 to 0.25, P=0.03). The Eq-5d visual analogue scale was 8.7 points higher in the hemiarthroplasty group after 4 months (1.9 to 15.6, P=0.01). After 12 and 24 months the percentage scoring 95 or 100 on the Barthel index was higher in the hemiarthroplasty group (relative risk 0.67, 0.47 to 0.95, P=0.02. and 0.63, 0.42 to 0.94, P=0.02, respectively). Complications occurred in 56 (50%) patients in the internal fixation group and 16 (15%) in the hemiarthroplasty group (3.44, 2.11 to 5.60, P<0.001). In each group 39 patients (35%) died within 24 months (0.98, 0.69 to 1.40, P=0.92) Conclusions Hemiarthroplasty is associated with better functional outcome than internal fixation in treatment of displaced fractures of the femoral neck in elderly patients. Trial registration NCT00464230.

Mechanisms of Anterior Cruciate Ligament Injury in World Cup Alpine Skiing: A Systematic Video Analysis of 20 Cases

Background: There is limited insight into the mechanisms of anterior cruciate ligament injuries in alpine skiing, particularly among professional ski racers. Purpose: This study was undertaken to qualitatively describe the mechanisms of anterior cruciate ligament injury in World Cup alpine skiing. Study Design: Case series; Level of evidence, 4. Methods: Twenty cases of anterior cruciate ligament injuries reported through the International Ski Federation Injury Surveillance System for 3 consecutive World Cup seasons (2006-2009) were obtained on video. Seven international experts in the field of skiing biomechanics and sports medicine related to alpine skiing performed visual analyses of each case to describe the injury mechanisms in detail (skiing situation, skier behavior, biomechanical characteristics). Results: Three main categories of injury mechanisms were identified: slip-catch, landing back-weighted, and dynamic snowplow. The slip-catch mechanism accounted for half of the cases (n = 10), and all these injuries occurred during turning, without or before falling. The skier lost pressure on the outer ski, and while extending the outer knee to regain grip, the inside edge of the outer ski caught abruptly in the snow, forcing the knee into internal rotation and valgus. The same loading pattern was observed for the dynamic snowplow (n = 3). The landing back-weighted category included cases (n = 4) where the skier was out of balance backward in flight after a jump and landed on the ski tails with nearly extended knees. The suggested loading mechanism was a combination of tibiofemoral compression, boot-induced anterior drawer, and quadriceps anterior drawer. Conclusion: Based on this video analysis of 20 injury situations, the main mechanism of anterior cruciate ligament injury in World Cup alpine skiing appeared to be a slip-catch situation where the outer ski catches the inside edge, forcing the outer knee into internal rotation and valgus. A similar loading pattern was observed for the dynamic snowplow. Injury prevention efforts should focus on the slip-catch mechanism and the dynamic snowplow.

Injuries among male and female World Cup alpine skiers

Background: Limited knowledge exists on injuries among professional alpine skiers. Objective: To describe the risk of injury and the injury pattern among competitive World Cup alpine skiers during the competitive season. Methods: Retrospective interviews were performed with all World Cup athletes from 10 nations at the end of the 2006–7 and 2007–8 winter seasons, and all acute injuries occurring during the 4.5-month competitive season were recorded. If the athlete was not present, their coaches or medical personnel were interviewed. Results: A total of 191 acute injuries were recorded among 521 World Cup alpine skiers. As many as 86 injuries (45%) occurred during World Cup/World Ski Championship competitions, corresponding to an injury rate of 9.8 injuries per 1000 runs (95% CI 7.8 to 11.9). The injury rate was found to increase with increasing speed (slalom 4.9 injuries per 1000 runs, 95% CI 2.5 to 7.4—giant slalom 9.2, 5.1 to 13.3—super-G 11.0, 5.2 to 16.8—downhill 17.2, 11.6 to 22.7). The most frequently injured body part was the knee, with 68 injuries (36%), and 37 of these were severe. The overall injury rate was higher in males than in females, but not for knee injuries. Conclusions : The risk of injury among World Cup athletes in alpine skiing is even higher than previously reported. The knee is the most commonly injured body part and with many severe injuries. Injury rate increased with a higher speed and was higher among males than in females.

Benign response to particles of diamond and Sic: bone chamber studies of new joint replacement coating materials in rabbits

Wear particles from total joint replacements are thought to accelerate prosthetic loosening. Diamond coating may improve the smoothness and wear characteristics of the femoral head component of total hip replacements, and thus increase their longevity. The brittleness of a thin diamond coat may be overcome by using an SiC-whisker diamond composite. This study describes the reactions of regenerating bone tissue to phagocytosable particles of diamond and SiC, using implanted bone harvest chambers in rabbits. The particles were dispersed in hyaluronan and introduced into a canal transversing the implant. The tissue that entered the canal during the following 3 weeks was then harvested. In previous studies using this model, particles of high density polyethylene, bone cement and chromium-cobalt all caused an inflammatory reaction and a marked decrease in the amount of ingrown bone. In the present study, neither the diamond nor the SiC particles caused any decrease in bone formation. It appears that particles of diamond and SiC are comparatively harmless.

Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture.

Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all‐cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow‐up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was ∼6 wk. Posthoc analyses were performed by dividing the study population into 2‐wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2‐wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2‐wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low‐trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.

Biocompatibility of silicon carbide in colony formation test in vitro

Abstract We studied the possible use of silicon carbide (SiC) as a ceramic coating material of titanium-based total hip replacement (THR) implants. The idea is to prevent wear debris formation from the soft titanium surface. SiC is a hard and tightly bonding ceramic surface material, and because of these physical properties it is not easily degradable, as is the case with hydroxyapatite. Our previous in vivo and in vitro studies have indicated that SiC and hydroxyapatite are equally biocompatible regarding particle size for phagocytosis. The present cytotoxicity test using JCRB0603 cells showed that 5 μm SiC particles inhibited colony outgrowth by one-third (67% + 10% vs control), while SiC-coated pins did not cause any inhibition and acted similarly to uncoated titanium pins. The results support the hypothesis that SiC is a promising ceramic THR implant coating material.

Human monocytes stimulation by particles of hydroxyapatite, silicon carbide and diamond: in vitro studies of new prosthesis coatings

Aseptic loosening due to wear and debris formation constitutes the major problem in longevity of joint replacements. Diamond coated onto the prosthesis surface may reduce wear, owing to its excellent tribological properties. A thin diamond coating may be brittle, and we plan eventually to reinforce it with silicon carbide whiskers (SiC). In the present study we compared particles of diamond, SiC and hydroxyapatite (HA) in serum-free cultures of human monocytes. All particles were found to be phagocytozed, and monocyte morphology changed except after the ingestion of diamond. Interleukin-1 beta production was increased on average 30-fold and 38-fold in cultures exposed to HA and SiC, respectively, compared to control and diamond cultures (n = 6). Addition of the phagocytosis inhibitor cytochalasin B inhibited the morphological changes of the monocytes and reduced interleukin-1 beta production. In some experiments particles of polymethylmethacrylate were also included, and the interleukin-1 beta stimulation was in the same range as after HA and SiC stimulation. The results show that diamond particles in serum-free monocyte culture are inert, while SiC and HA have a stimulatory effect comparable to polymethylmethacrylate. With its excellent tribological and biocompatible properties, future studies with diamond coating are warranted.