Torsten Johansson

Teriparatide for acceleration of fracture repair in humans: A prospective, randomized, double‐blind study of 102 postmenopausal women with distal radial fractures

Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 µg dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once‐daily injections of placebo (n = 34) or teriparatide 20 µg (n = 34) or teriparatide 40 µg (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparatide 40 µg versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparatide 20 µg and 40 µg, respectively (overall p = .015). There was no significant difference between the teriparatide 40 µg versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparatide 40 µg versus 20 µg (p = .053); however, the time to healing was shorter in teriparatide 20 µg than placebo (p = .006). The primary hypothesis that teriparatide 40 µg would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparatide 20 µg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study.

Internal fixation versus total hip arthroplasty in the treatment of displaced femoral neck fractures. A prospective randomized study of 100 hips

100 patients 75 years or older, with displaced femoral neck fractures, were randomly assigned to osteosynthesis with two parallel and percutaneously inserted screws (Olmed) or total hip arthroplasty (Lubinus IP). Mean age was 84 (75-101) years, 74% were women and 45% had mental dysfunction. General complications were commoner in the arthroplasty group but the mortality rates did not differ. In the osteosynthesis group, fracture complications were seen in 27/50 hips. In the arthroplasty group, dislocation was the main complication and occurred in 11/50 cases. At 3 months and after 1 year, the Harris Hip Scores were significantly better in the arthroplasty group. When mental dysfunction was present, the dislocation rate after arthroplasty was 32%, whereas the reoperation rate after osteosynthesis was 5%. The opposite pattern of complications was found in patients with normal mental function, 12% versus 60%. The 2-year mortality rate among those with mental dysfunction was 26/45, compared to 7/55 of those with normal function (p < 0.001). We conclude that total hip arthroplasty should be considered for a displaced femoral neck fracture in old patients with normal mental function and high functional demands.

Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients.

Background A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved. Patients and methods 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb con-centration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually. Results The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred. Interpretation Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.

Teriparatide improves early callus formation in distal radial fractures

Background Teriparatide (parathyreoid hormone; PTH 1-34) increases skeletal mass in humans and improves fracture healing in animals. A recent randomized multicenter trial of nonoperated distal radial fractures showed a moderate shortening of the time to restoration of cortical continuity by treatment with 20 μg (low-dose) teriparatide per day, but not with 40 μg (high-dose). As radiographic cortical continuity appears late in the healing process, perhaps too late for clinical relevance, we studied the qualitative appearance of the callus 5 weeks after fracture. Methods One third of the patients of the international trial were treated at Linköping University Hospital. The multicenter trial did not evaluate early callus formation. We therefore made a blinded qualitative scoring of the callus at 5 weeks in our 27 patients. Callus formation was arbitrarily classified as rich, intermediate, or poor. Results 9 patients were classified as rich (none had received placebo, 3 low-dose teriparatide, and 6 high-dose teriparatide). 9 patients were classified as intermediate (1 had received placebo, 5 low-dose, and 3 high-dose). 9 patients were classified as poor (7 had received placebo, 1 low-dose, and 1 high-dose) (p < 0.001). Interpretation This is a post hoc subgroup analysis of an outcome variable, which was not in the official protocol. The results must therefore be interpreted with caution. However, in combination with the results of the larger trial, the data suggest that radiographic quality at an early time point might be a sensitive variable, perhaps better than time to cortical continuity. Moreover, teriparatide appeared to improve early callus formation in distal radial fractures.

Mild hypothermia does not increase blood loss during total hip arthroplasty

Background: The effects of mild hypothermia on blood loss are little known.

A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified hemoglobin (hemospan®) in patients undergoing major orthopedic surgery

Background:Hemospan® (Sangart Inc., San Diego, CA), a polyethylene glycol–modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia. Methods:Ninety male and female patients, American Society of Anesthesiologists physical status I–III, aged 50–89 yr, in six Swedish academic hospitals were randomly assigned to receive either 250 or 500 ml Hemospan or Ringer’s acetate (30 patients/group) before induction of spinal anesthesia. Safety assessment included vital signs and Holter monitoring from infusion to 24 h, evaluation of laboratory values, and fluid balance. The hypothesis to be tested was that the incidence of adverse events would be no more frequent in patients who received Hemospan compared with standard of care (Ringer’s acetate). Results:Three serious adverse events were noted, none of which was deemed related to study treatment. Liver enzymes, amylase, and lipase increased transiently in patients in all three groups. There were no significant differences in electrocardiogram or Holter parameters, but there was a suggestion of more bradycardic events in the treated groups. Hypotension was less frequent in the treated patients compared with controls. Conclusions:In comparison with Ringer’s acetate, Hemospan mildly elevates hepatic enzymes and lipase and is associated with less hypotension and more bradycardic events. The absence of a high frequency of serious adverse events suggests that further clinical trials should be undertaken.

The total costs of a displaced femoral neck fracture: comparison of internal fixation and total hip replacement: A randomised study of 146 hips

We randomised 143 patients –age 75 years or older–with displaced femoral neck fracture to either internal fixation or total hip replacement (THR) and compared the socio-economic consequences. In the internal fixation group, 34 of 78 hips underwent secondary surgery. In the THR group, 12 of 68 hips dislocated, the majority in mentally impaired patients. We calculated the total hospital costs for two years after operation. When secondary surgery was included, there was no difference in costs between the internal fixation and THR groups, or between the mentally impaired and lucid subgroups. The costs to the community were calculated comparing the baseline cost before surgery with the average cost per month during the first postoperative year. No difference was found between the treatment groups. The Harris hip scores were higher in the THR group, and pain was more common in the internal fixation group. In lucid patients, THR gives a better clinical result at the same cost.RésuméNous avons randomisé 143 malades-âgés de 75 ans ou plus– avec une fracture du col fémoral déplacée traitée par fixation interne ou remplacement totale de la hanche et avons comparé les conséquences socio-économiques. Dans le groupe de la fixation interne, 34/78 hanches ont subi une chirurgie secondaire. Dans le groupe PTH, 12/68 hanches se sont luxées, la majorité chez des malades mentalement affaiblis. Nous avons calculé les coûts totaux d’hospitalisation jusqu’à deux années postopératoires. Quand la chirurgie secondaire a été incluse, il n’y avait aucune différence dans les coûts entre la fixation interne et le groupe PTH, ou entre les sous-groupes mentalement affaibli et lucides. Les coûts municipaux ont été calculés en comparant le coût de base avant chirurgie avec le coût moyen par mois pendant la première année postopératoire. Aucune différence n’a été trouvée entre les groupes de traitement. Le score de hanche de Harris étaient supérieur dans le groupe PTH et la douleur était plus fréquente dans le groupe de la fixation interne. Chez les malades lucides, la PTH donne un meilleur résultat clinique au même coût.

Internal fixation compared with total hip replacement for displaced femoral neck fractures: a minimum fifteen-year follow-up study of a previously reported randomized trial.

BACKGROUND Prospective randomized studies comparing internal fixation and a cemented hip replacement in the treatment of displaced femoral neck fractures have shown favorable short-term results for prosthetic replacement. The present report compares the results after a minimum of fifteen years. METHODS From 1994 to 1998, 143 patients (146 hips) were randomized to closed reduction and internal fixation with two screws (n = 78) or a cemented total hip replacement (n = 68). The average age of the patients was eighty-four years (range, seventy-five to 101 years), and 38% were classified as mentally impaired. Failure after internal fixation was defined as early redisplacement, nonunion, symptomatic segmental collapse, or deep infection. In the arthroplasty group, failure was defined as two dislocations or more, implant loosening, deep infection, or a periprosthetic fracture. RESULTS For the lucid patients, the failure rate was 55% after internal fixation compared with 5% after total hip replacement. For patients with mental impairment, it was 16% in both groups. CONCLUSIONS Total hip replacement is superior to internal fixation in the treatment of a displaced femoral neck fracture.

Nutritional status and functional capacity after femoral neck fractures: A prospective randomized one-year follow-up study

The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures. A further aim was to evaluate the effect of nutritional support. One hundred patients were randomly assigned to treatment with either primary total hip arthroplasty (THA) or osteosynthesis. Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food. Nutritional state and functional capacity were examined at baseline, one and three months, and one year after the operation. Pain was examined at three months and one year. The effect of nutritional intervention was equal within both surgical groups. Logistic regression showed that the dependent variable “living at one year” was significantly associated with serum albumin levels at one month. Advanced age, mental impairment and deteriorated nutritional status were predominant in the non-survivors. Overall, the primary THA group performed better compared with the osteosynthesis group concerning weight change over time, locomotion and pain. This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate.

PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures

Background and purpose — There is solid evidence from animal experiments that parathyroid hormone (PTH) improves fracture healing. So far, only 3 papers on PTH and fracture repair in humans have been published. They suggest that PTH may enhance fracture healing, but the results do not appear to justify specific clinical recommendations. This study was carried out to determine whether teriparatide enhances fracture healing of proximal humerus fractures. Patients and methods — 40 post-menopausal women with a proximal humerus fracture were randomized to either daily injections with 20 µg teriparatide (PTH 1-34 (Forteo)) for 4 weeks or control treatment. At randomization, the patients were asked to assess how their pain at rest and during activity (visual analog scale (VAS)) and also function (DASH score) had been prior to the fracture. At 7 weeks and again at 3 months, their current state was assessed and the tests were repeated, including radiographs. 2 radiologists performed a blind qualitative scoring of the callus at 7 weeks. Callus formation was arbitrarily classified as ”normal” or “better”. Results — 39 patients completed the follow-up. The radiographic assessment showed a correct correlation, “better” in the teriparatide group and “normal” in the control group, in 21 of the 39 cases. There were no statistically significant differences in pain, in use of strong analgesics, or in function between the groups at the follow-up examinations. Interpretation — There were no radiographic signs of enhanced healing or improved clinical results in the group treated with teriparatide