Kalevi Hietaniemi

An experimental model for non-union in rats

Few studies of the biological changes which occur in impaired fracture repair and non-union have been carried out, and creating an appropriate model for advanced biochemical studies of non-union has proved to be a demanding task. This paper presents a standardized experimental model for producing non-union in rat femurs, for use in biochemical studies of non-union. A mid-diaphyseal fracture with a rotationally unstable fixation was performed in rats with a mean weight of over 330 g and mean age of over 10 weeks. Radiologically and histologically (Alcian blue and Safranin O stainings) the signs of undisturbed fracture healing were observed until 3 weeks after the fracture. Thereafter there was evidence that chondrocytic activity ceased, with no signs of formation of calcifying bridging callus. From the seventh week onwards, all elements necessary for a calcifying callus were lost; and the histological picture tended to be of scar tissue bond between the fracture ends.

Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: a randomized controlled trial

BackgroundArthroscopy is often used to treat patients with chronic patellofemoral pain syndrome (PFPS). As there is a lack of evidence, we conducted a randomized controlled trial to study the efficacy of arthroscopy in patients with chronic PFPS.MethodsA total of 56 patients with chronic PFPS were randomized into two treatment groups: an arthroscopy group (N = 28), treated with knee arthroscopy and an 8-week home exercise program, and a control group (N = 28), treated with the 8-week home exercise program only. The arthroscopy included finding-specific surgical procedures according to current recommendations. The primary outcome was the Kujala score on patellofemoral pain and function at 9 months following randomization. Secondary outcomes were visual analog scales (VASs) to assess activity-related symptoms. We also estimated the direct healthcare costs.ResultsBoth groups showed marked improvement during the follow-up. The mean improvement in the Kujala score was 12.9 (95% confidence interval (CI) 8.2–17.6) in the arthroscopy group and 11.4 (95% CI 6.9–15.8) in the control group. However, there was no difference between the groups in mean improvement in the Kujala score (group difference 1.1 (95% CI -7.4 - 5.2)) or in any of the VAS scores. Total direct healthcare costs in the arthroscopy group were estimated to exceed on average those of the control group by €901 per patient (p < 0.001).ConclusionIn this controlled trial involving patients with chronic PFPS, the outcome when arthroscopy was used in addition to a home exercise program was no better than when the home exercise program was used alone.Trial registrationCurrent Controlled Trials ISRCTN 41800323

NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

Neurofibromatosis type 1 (NF1) is an inherited disease with an incidence of about 1:3000 worldwide. Approximately half of all patients with NF1 present osseous manifestations, which can vary from mild to severely debilitating changes such as congenital pseudarthrosis. In the present study, fracture healing of mouse tibia was followed and specimens were collected 5, 9, 14, and 22 days postoperatively. Experimental pseudarthrosis of rat was followed up to 15 weeks postoperatively. In situ hybridization and immunohistochemistry were used to demonstrate expression of NF1 tumor suppressor and phosphorylated p44/42 mitogen-activated protein kinase (MAPK), an indicator of the Ras-MAPK pathway. The results showed that ossified callus was formed in mouse fracture 22 days after the operation. The final outcome of rat pseudarthrosis was detected 9 weeks after the operation, presenting abundant cartilaginous callus at the pseudarthrosis. NF1 gene expression was noted in the maturing and in the hypertrophic cartilages during normal mouse fracture healing, and in rat pseudarthrosis. Phosphorylated p44/42 MAPK was detected in a subpopulation of the hypertrophic chondrocytes in both models. Furthermore, positive labeling for NF1 mRNA and protein was detected in endothelium in both the pseudarthrosis and in the fracture. In conclusion, NF1 gene expression and function are needed for normal fracture healing, possibly restraining excessive Ras-MAPK pathway activation.

Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: 5-year follow-up

Objective To study the long-term outcome of arthroscopy in patients with chronic patellofemoral pain syndrome (PFPS), the authors conducted a randomised controlled trial. The authors also investigated factors predicting the outcome in patients with PFPS. Methods Fifty-six patients with PFPS were randomised into two groups: an arthroscopy group (N=28), treated with knee arthroscopy and an 8-week home exercise programme, and a control group (N=28), treated with a similar 8-week home exercise programme only. The primary outcome was the Kujala score on pain and function at 5-year. Secondary outcomes were visual analogue scales (VASs) to assess activity-related symptoms. Results According to the Kujala score, both groups showed a marked improvement during the 5-year follow-up: a mean improvement of 14.7 (95% CI 9.9 to 19.4) in the arthroscopy group and 13.5 (95% CI 8.1 to 18.8) in the controls. No differences between the groups in mean improvement in the Kujala score (group difference 1.2 (95% CI –8.4 to 6.1)) or in the VAS scores were found. None of the investigated factors predicted the long-term outcome, but in most of the cases the treatment result immediately after the exercise programme remained similar also after the 5-year follow-up. Conclusion Our RCT, being the first of its kind, indicates that the 5-year outcome in most of the patients with chronic PFPS treated with knee arthroscopy and home exercise programme or with the home exercise programme only is equally good in both groups. Some of the patients in both groups do have long-term symptoms. Trial registration Current Controlled Trials ISRCTN 41800323.

Is longer waiting time for total knee replacement associated with health outcomes and medication costs? Randomized clinical trial.

BACKGROUND The aim of this prospective randomized study was to evaluate the effect of waiting time (WT) on health-related quality of life (HRQoL), knee pain and physical function, and the use and costs of medication of patients awaiting total knee replacement. METHODS When placed on the waiting list, 438 patients were randomized into a short waiting time (SWT ≤ 3 months) or a nonfixed waiting time (NFWT > 3 months) group. HRQoL was measured by the 15D, and pain and physical function by modified Knee Society Clinical Rating System at baseline, admission, and 3 and 12 months postoperatively. The costs of medication due to osteoarthritis were calculated at the same measurement points. All analyses were performed using the intention-to-treat principle. RESULTS The mean WT was 94 and 239 days in the SWT and NFWT groups, respectively. Apart from higher weekly cost of medication in the SWT group at admission and better HRQoL in the NFWT group 1 year postoperatively, there were no statistically significant differences between the groups in other outcomes during the follow-up. CONCLUSION Those in the SWT group had higher weekly costs of medication at admission, and reached better HRQoL 3 months earlier than those in the NFWT group, but the latter had better HRQoL after operation. Otherwise, the length of WT was not associated with different health and HRQoL outcomes in the groups.

The Effect of Waiting Time on Health‐Related Quality of Life, Pain, and Physical Function in Patients Awaiting Primary Total Hip Replacement: A Randomized Controlled Trial

OBJECTIVE This prospective randomized study assessed the effect of waiting time (WT) on health outcomes in Finnish patients admitted to hospital for primary total hip replacement (THR). METHODS A total of 395 consecutive patients with a need for a primary THR because of osteoarthritis and who were placed on the waiting list between August 2002 and November 2003. After placement on the waiting list, the patients were randomly assigned to a short WT (<or=3 months) group (n = 174) or a nonfixed WT group (n = 221). The patients completed self-administered questionnaires at the time of placing on the waiting list and at hospital admission. Health-related quality of life was measured by the generic 15D instrument. Hip pain and function were measured by the patient self-report Harris hip score (HHS). RESULTS Of the 395 patients, 312 (79%) completed the follow-up (140 patients with short and 172 with nonfixed WT). At admission, the mean 15D scores for patients with short and nonfixed WT were 0.784 and 0.783, respectively. In the intention-to-treatment analysis, the difference between the groups (Delta 0.001, 95% confidence interval [CI]: -0.019 to 0.021) was not statistically significant or clinically important. The mean self-report HHS in patients with short WT was 43.5, and among those with nonfixed WT was 41.9. The difference (Delta 1.6, 95% CI: -1.77 to 4.87) was not statistically significant. CONCLUSIONS Both generic and disease-specific measures revealed that longer WTs did not result in poorer health status at admission.

The effect of waiting time on health and quality of life outcomes and costs of medication in hip replacement patients: a randomized clinical trial

OBJECTIVE To evaluate the effect of waiting time on health and quality of life outcomes and costs of medication in total hip replacement (THR) patients in a randomized clinical trial. METHODS 395 THR patients were recruited into the study. When placed on the waiting list, patients were randomized into a short (< or =3 months) or a non-fixed waiting time (NFWT) (>3 months) group. In the final analyses 309 patients (179 women) with a mean age of 65 years were included. Health-related quality of life (HRQoL) (generic 15D), and pain and function (modified Harris Hip Score (HHS)) were calculated when placed on the waiting list, at hospital admission, and at 3 and 12 months postoperatively. The costs of disease-specific medication were calculated at the same measurement points. All analyses were performed using the intention-to-treat (ITT) principal. RESULTS Of the recruited patients, 309 (78%) completed the follow-up (short group 140 and non-fixed group 169 patients). The mean waiting time was 74 days in the short and 194 days in the NFWT groups. In the ITT analyses there were no statistically significant differences between the groups in the weekly use and costs of medication, HRQoL or HHS at baseline, at admission, or 3 or 12 months after surgery. The only difference was in total medication costs during the waiting time period, at EUR 83 and 171, respectively. CONCLUSIONS The length of the waiting time did not generate different effects on the studied health and quality of life outcomes of the randomized groups. However, those in short waiting time group reached earlier better HRQoL.

Major fibrillar collagens and fibronectin in an experimental nonunion: an immunohistochemical study.

We studied in a rat pseudoarthrosis model the time sequence of expression and distribution of fibronectin and collagens I, II, III and V. Collagens and fibronectin were immunolocalized at the light microscopic level. The major difference from the normal healing pattern was the extension of collagen II and cartilage into the interfragmentary area and at the circumference of the periosteal callus, without any bridging chondral or bony elements in the fracture gap. The formation of a fibrous bond, consisting mostly of collagen III and fibronectin, was observed. This speaks in favor of the failure of the multipotentional mesenchymal stem cells to change the fracture-healing process towards fibroblast proliferation and the production of tissue unable to mineralize. The decisive zone for mineralization of the callus appeared to be the area of the hypertrophied chondrocytes near the periosteal ossification front.

Connective tissue parameters in experimental nonunion

A previously developed experimental model for producing nonunions in rats was used to study the biochemical changes of connective tissue parameters in impaired fracture repair. The model is based on rotational instability between the fracture fragments. A mid-diaphyseal femoral osteotomy was performed on 30 male rats and fixed with a loose-fitting intramedullary nail. The rats were killed 1, 2, 3, 7, 9, and 12 weeks postoperatively, and the development of nonunions was verified with radiographs. The calluses were dissected free and set for biochemical analysis. The contents of nitrogen, hydroxyproline, calcium, and phosphorous, as well as the RNA/DNA ratio, were determined. It appeared that in the impaired fracture repair there is an extended matrix production phase continuing until 7 weeks postoperatively. Simultaneously, the number of callus cells increased, indicating an extended expression of the mitotic signals for callus cells. The net synthesis of collagen matrix seemed to be sufficient, but the mineral binding capacity of the newly synthetised collagen was impaired. Later, the cessation of chondrogenic and osteogenic activity could be observed with the formation of nonmineralized fibrous tissue between the fracture fragments.

Is longer waiting time associated with health and social services utilization before treatment? A randomized study

Objective: To determine whether longer waiting time for major joint replacement is associated with health and social services utilization before treatment. Methods: When placed on the waiting list, patients were randomized to short (≤3 months) or a non-fixed waiting time. Utilization measures were the use of home health care, rehabilitation and social services before treatment. Results: A total of 833 patients with osteoarthritis of the hip or knee joint were recruited into the study. Six hundred and twenty-two patients were included in the analysis. The majority of patients were not using any services before hospital admission for joint replacement surgery. The most commonly used service was unpaid home help provided by relatives, neighbours, friends and volunteers (informal care). In both groups, private support services were utilized more often than public ones. Patients with a short waiting time were more likely than those with a non-fixed waiting time to use rehabilitation (13.5% versus 8.2%, P = 0.032) and visiting care services (7.5% versus 3.9%, P = 0.054). Conclusions: Only a few patients used professional care. They were more likely to require informal care during the waiting time. A longer waiting time did not result in a higher utilization rate before admission for treatment.