Jaakko Kinnunen

Genome Scan for Predisposing Loci for Distal Interphalangeal Joint Osteoarthritis: Evidence for a Locus on 2q

The genetic contribution to common forms of osteoarthritis (OA) is well established but poorly understood. We performed a genome scan, using 302 markers for loci predisposing to distal interphalangeal joint (DIP) OA. To minimize genetic heterogeneity in our study sample, we identified siblings with a severe, radiologically defined phenotype from the nationwide registers of Finland. In the initial genome scan, linkage analysis in 27 sibships gave a pairwise LOD score (Z) >1.00 with nine of the screening markers. In the second stage, additional markers and family members were genotyped in these chromosomal regions. On 2q12-q13, IL1R1 resulted in Z=2.34 at recombination fraction (theta) 0, allowing a dominant mode of inheritance. Association analysis of markers D2S2264, IL1R1, D2S373, and D2S1789 jointly provided some evidence for a shared haplotype among the affected individuals (P value of.012). Also, multipoint nonparametric linkage analysis yielded a P value of.0001 near the locus IL1R1 and P=.0007 approximately 20 cM telomeric near marker D2S1399, which, in two-point analysis, gave Z=1.48 (straight theta=. 02). This chromosomal region on 2q harbors the interleukin 1 gene cluster and, thus, represents a good candidate region for inflammatory and autoimmune disorders. Three additional chromosomal regions-4q26-q27, 7p15-p21, and Xcen-also provided some evidence for linkage, and further analyses would be justified to clarify their potential involvement in the genetic predisposition to DIP OA.

Bone changes after experimental osteotomies fixed with absorbable self-reinforced poly-l-lactide screws or metallic screws studied by plain radiographs, quantitative computed tomography and magnetic resonance imaging

The healing of the distal femoral osteotomy fixed with self-reinforced poly-L-lactide (SR-PLLA) or metallic screws in 16 rabbits was evaluated with plain radiographs, quantitative computed tomography and magnetic resonance imaging (MRI). At 36 weeks in the metallic fixation there was significantly more external callus than in the SR-PLLA fixation. On the metallic fixation side the cortical bone mineral density was significantly lower than on the non-operated side at 6 weeks as well as at 36 weeks. This decrease was not found in the SR-PLLA fixation. On the MRI on T1-weighted images a dark zone (signal void), and on the T2-weighted images a bright zone (increased signal intensity), was seen surrounding the screws, indicating oedema. At 36 weeks these oedematous zones were significantly smaller in the SR-PLLA fixation group than in the metallic one. The results give indirect evidence towards a more rapid and better osteotomy healing with the more physiologically elastic SR-PLLA screws than with the metallic screws. Fixation with SR-PLLA screws may prevent stress-protection atrophy and weakening of the fixed bone usually caused by the rigid metallic fixation.

BIOACTIVE GLASS GRANULES AND PLATES IN THE RECONSTRUCTION OF DEFECTS OF THE FACIAL BONES

Non-vascularised bone grafts that are used for reconstruction of skeletal deformities of the face after trauma or tumour surgery are prone to resorption. The outcome may, therefore, not be what was expected. Bone was reconstructed with bioactive glass S53P4 granules and plates at 36 sites in 13 patients. The behaviour of the material was compared with that of bone grafts at 16 sites in the same patients. Bioactive glass granules were used in facial bone defects in subperiosteal pockets and to obliterate frontal sinuses, whereas bioactive glass plates were used mostly in orbital wall reconstruction. Clinical examination, middle face radiographs, and computed tomograms (CT) showed that the material was well tolerated. A third of the glass granules and a quarter of the membranous bone grafts that were fixed with miniplates retained their original size. The glass plates did not change in size. Bone contact to the host bone was found more often with the bioactive glass plates than with the bioactive glass granules or the bone grafts. Both the glass plates and the bone grafts retained their density, but there was a reduction in density of the glass granules. The clinical outcome showed no relapses after one years follow up. No further operations were needed because of the material used.

Prolonged low-back pain in young athletes: a prospective case series study of findings and prognosis.

Abstract We investigated the prognosis of low-back pain and the association of clinical symptoms and anatomic findings among young athletes. Consecutive patients, aged between 12 and 18 years, who had low-back pain that had interfered with their training for at least 4 weeks were included in the case series. All the patients participated in a standardized interview and clinical examination, and plain radiographs and magnetic resonance images were also obtained. Most patients also participated in technetium bone scan examination. In 15 out of 19 subjects there were anatomic abnormalities that corresponded with the location and type of clinical symptoms. Twelve subjects had changes in the disk-vertebral end plate complex and eight had a positive bone scan indicative of posterior vertebral arch stress reaction. Six out of eight boys and two out of 11 girls had stress reaction (P = 0.043). Restriction of painful activities was recommended to all subjects, restriction of activities and the use of a dynamic low-back brace for the first 3 months was recommended to patients with posterior vertebral arch stress reaction. The self-reported intensity of low-back pain (scale 0–100) among all the patients was 69 ± 16 (mean ± SD) at baseline and 18 ± 21 at the 1-year follow-up (P < 0.0001). In conclusion, the reasons for prolonged back pain among young athletes are usually established by imaging studies. A knowledge of anatomic abnormalities may help in tailoring training programmes and avoiding the progression of changes during growth. Simple restriction of painful activities usually leads to good recovery.

In vivo monitoring of the degradation process of bioresorbable polymeric implants using magnetic resonance imaging.

The degradation of a bioresorbable poly(L-lactide) osteosynthesis plug after fixation of a transferred coracoid bone block using the Bristow-Latarjet procedure was examined by means of magnetic resonance (MR) imaging. There were 15 patients with a mean follow-up time of 38 months (range 34-42 months). The gross geometry of the biomaterial plug remained unaltered on the MR images. The bone marrow signal reached the implant surfaces in all cases, and no signs of liquid phase around the implant could be discerned. The implants themselves were visible as homogeneous low signal intensity (SI) black linear structures when compared to the surrounding bone, which had a much higher SI. The mean implant SI was 18.2 (s.d. +/- 6.6), that of the scapular bone 48.9 (s.d. +/- 14.3) and that of the background 4.3 (s.d. +/- 1.5). The SI of a newly manufactured intact implant was 5.7. Serial plain radiographs showed no decreased bone density or focal osteolytic lesions around the poly(L-lactide) expansion plug. The implant channel was discernible on most of the radiographs and a sclerotic rim was detected to outline the implant profile in some of the projections of plain radiographs at each follow-up examination. Computer tomography scans on five patients 3 years postoperatively also revealed a discernible implant channel outlined with a sclerotic rim. The radiographic appearance of the radiolucent implant channel did not change over the follow-up period. Summarizing the present findings, MR imaging seems to be able to visualize poly(L-lactide) implants within the bone. Actually, at present it is the only method available to study the degradation process of implants made of this polymer in humans. No signs of degradation of or of an osteolytic foreign-body reaction to poly(L-lactide) at the host tissue-implant interface could be observed within the follow-up times of this study.

Diagnostic performance of low field MRI in acute knee injuries

The diagnostic performance of low field (0.1 T) magnetic resonance imaging (MRI) was studied prospectively and double-blindly among 33 patients with acute knee injuries. The subsequent arthroscopy was the golden standard. For lesions of the medial meniscus low field MR had a sensitivity of 88% and a specificity of 80%; for lesions of the lateral meniscus the sensitivity was 25% and the specificity 97%. For anterior cruciate ligament tears, low field MRI had a sensitivity of 83% and a specificity of 85%. The specificity for posterior cruciate ligament tears was 97%. The performance of low field MRI equalled that reported earlier for high field MRI, the only exception being the sensitivity for lateral meniscus lesions.

MR imaging of fatigue stress injuries to bones: intra- and interobserver agreement

The aim of this study was to determine the validity of MR imaging (MRI) in the assessment of stress-related injuries to bone.MR images of 50 military recruits (8 females and 42 males; 18-27 (mean 20) years of age) were retrospectively evaluated twice for stress injuries to bone by 4 radiologists (2 musculoskeletal radiologists, 2 radiology residents). Coronal T1-weighed (T1W) and STIR images, as well as axial and coronal T2-weighted (T2W) fat-suppressed images were taken using a 1.0T scanner. Rates for sensitivity, specificity, and accuracy of MRI of the stress-related injuries were calculated. Intraobserver and interobserver agreement was determined with kappa statistics. Rates for MRI sensitivity were 27-96%, for specificity 65-100%, and for diagnostic accuracy 58-97%. Lowest rates were seen when reading T1W images and highest when reading STIR images. Readers showed moderate to excellent intraobserver agreement (kappa 0.75-0.95). Interobserver agreement was fair to excellent (kappa 0.41-0.91), and the lowest values were seen in the interpretation of T1W images. Normal findings could be differentiated from various grades of stress injury to bone.MRI is a valid means of revealing the presence of stress injuries to bone and their staging. Observer agreement is good to excellent when using T2W images and STIR images, while T1W images are of lesser value.

Natural coral as bone-defect-filling material.

Natural coral (NC) has been studied experimentally and clinically as a bone substitute, but its resorption rate and possible replacement by bone still need to be defined in humans. In this study bicortical bone was harvested from the iliac crest of 10 patients. The defect was filled with a NC block, and changes were monitored by X-rays and quantitative CT scans for a mean of 2.1 years. A biopsy was taken at 1 year. The purpose of the study was to investigate the resorption rate and pattern of NC (Porites) implants and the replacement, if any, of the implant by new bone. The blocks underwent centripetal resorption, but all the blocks still could be detected by X-rays and CT scans at the end of the follow-up period. The density of the remaining block did not change. Seven of the 10 implants were smaller than 50% of their original size at the end of the study. Bone ingrowth could be observed only in two of seven biopsies. One implant had to be removed after 1.7 years due to infection. The study shows that resorption of natural coral proceeds centripetally and apparently more rapidly when accompanied by tissue ingrowth. None of the blocks resorbed completely, and the defect at the iliac crest had not been restored by the end of the study.

Joint-specific twin and familial aggregation of recalled physician diagnosed osteoarthritis

In our three-stage questionnaire study we investigated patterns of twin and familial aggregation of osteoarthritis (OA) for commonly affected joints. The baseline questionnaire study of the Finnish Twin Cohort was performed in 1975. In 1990, 4095 twin pairs of the same gender born 1930-1957 responded to a questionnaire and reported whether they had OA diagnosed by a physician. In 1996 both twins of 266 pairs of which at least one had reported OA in 1990 responded to a detailed questionnaire on joint-specific OA, including family history of OA. In male pairs shared (non-genetic) familial effects accounted for 37% of the total variance in liability to OA and unshared environmental effects for 63%. In female pairs additive gene effects explained 44% of the variance in liability to OA, and unshared environmental effects for 36%. Familial aggregation of finger and knee OA was clearly higher than that of hip OA. Twin-pair discordance for OA was, to some extent, associated with body-mass index, occupational loading and trauma. Our results indicate that genetic effects may be modulated by sex or by environmental factors distributed differently between men and women. Based on our joint-specific data finger and knee joints are the most optimal targets for studies of genetic factors predisposing to the development of OA.

Intramedullary fixation of distal femoral diaphyseal osteotomies with absorbable self-reinforced poly-L-lactide and metallic intramedullary rods assessed by plain radiographs, quantitative computed tomography, and magnetic resonance imaging: An experimental study in rabbits

Osteotomies of distal femoral diaphysis were fixed intramedullary with self-reinforced poly-L-lactide acid (SR-PLLA) rods in 19 and with metallic rods in 34 adult rabbits. The follow-up times were 8, 16, 24, and 48 weeks. Plain radiographs, computed tomography (CT), quantitative computed tomography (QCT), and magnetic resonance imaging (MRI) were used to evaluate the bone changes at two different levels of the osteotomy region. There were no significant differences in cortical bone density compared to the intact in the SR-PLLA fixed femurs at the osteotomy site. In the metallic-fixed femurs, the density values were significantly lower as compared to the contralateral femurs. There was a significant reduction of the cortical bone density values in SR-PLLA fixed femurs compared to the intact control side outside the osteotomy area at 8 (p = 0.01), at 16 (p = 0.0001), and at 24 weeks (p = 0.0003). In the metallic-fixed femurs significant reductions at 8 weeks (p = 0.02), at 16 weeks (p = 0.01), at 24 weeks (p = 0.009), and at 48 weeks (p = 0.002) were found compared with the intact control. MRI depicted well the SR-PLLA cases allowing studies without removal of the implant. On the contrary, abundant disturbing metallic artifacts were detected during investigation of the metallic-fixed femurs. In conclusion, our results indicated that CT is useful to evaluate the quality of reduction and internal fixation. Furthermore, the constant presence of internal metallic fixation seems to eventually cause osteoporosis in the cortical region of the femur. However, this stress protection effect of intramedullary fixation on the femoral diaphysis seems to be avoided by using an absorbable SR-PLLA rod, thus resulting in a better quality of bone when the osteotomies are healed.