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Background and purpose - Limb lengthening with an intramedullary motorized nail is a relatively new method. We investigated if lengthening nails are reliable constructs for limb lengthening and deformity correction in the femur and the tibia. Patients and methods - 50 lengthenings (34 Precice and 16 Fitbone devices) in 47 patients (mean age 23 years [11-61]) with ≥12 months follow-up are included in this study. 30 lengthenings were done due to congenital and 20 because of posttraumatic deformity (21 antegrade femora, 23 retrograde femora, 6 tibiae). Initial deformities included a mean shortening of 42 mm (25-90). In 15 patients, simultaneous axial correction was done using the retrograde nailing technique. Results - The planned amount of lengthening was achieved in all but 2 patients. 5 patients who underwent simultaneous axial correction showed minor residual deformity; unintentionally induced minor deformities were found in the frontal and sagittal plane. The consolidation index was 1.2 months/cm (0.6-2.5) in the femur and 2.5 months/cm (1.6-4.0) in the tibia. 2 femoral fractures occurred in retrograde femoral lengthenings after consolidation due to substantial trauma. There were 8 complications, all of which were correctable by surgery, with no permanent sequelae. Interpretation - Controlled acute axial correction of angular deformities and limb lengthening can be achieved by a motorized intramedullary nail. A thorough preoperative planning and intraoperative control of alignment are required to avoid residual and unintentionally induced deformity. In the femur relatively fast consolidation could be observed, whereas healing was slower in the tibia.

Introduction: Ludloff’s procedure for open reduction of congenital dislocation of the hip (CDH) is recommended for its minimal tissue damage, but is criticised for the risk of late avascular necrosis (AVN) of the femoral head. The aim of present study was primarily to assess the risk of late AVN of the femoral head and secondly the range of motion (ROM) of the hip and the quality of life in children following Ludloff’s procedure. Methods and materials: 13 hips in 11 children after Ludloff’s procedure due to CDH were included retrospectively from 1997 to 2005 at Aarhus University Hospital. Radiographs were evaluated for the presence of AVN of the femoral head and classified according to the Bucholz and Ogden classification, with type 2-4 having clinical relevance. A clinical examination included range of motion (ROM) and leg length discrepancy (LLD) measurements. The HAGOS hip questionnaire evaluated activity, participation and quality of life. Results: No severe type 3-4 AVN was observed. 2 type 2 and 5 type 1 were observed. AVN was observed in 7 of the 13 operated hips (54%). An 8.6° difference in flexion for unilaterally treated hips was observed (pConclusions: Only minor AVN of clinical importance was seen after Ludloff’s procedure.

Background and purpose — Hexapod ring fixators such as the Taylor Spatial Frame (TSF) have shown good outcomes. However, there have only been a few studies comparing the use of TSF with various etiologies of the deformity. We compared the use of TSF in congenital and acquired deformities in children. Patients and methods — We reviewed 213 lower extremity reconstructive procedures with the TSF in 192 patients who were operated between October 2000 and October 2015. 128 procedures (67 proximal tibiae, 51 distal femora, and 10 distal tibiae) in 117 children (median age 14 (4–18) years; 59 girls) fulfilled the inclusion criteria. 89 procedures were done in children with congenital deformities (group C) and 39 were done in children with acquired deformities (group A). Outcome parameters were lengthening and alignment achieved, lengthening index, complications, and analysis of residual deformity in a subgroup of patients. Results — Mean lengthening achieved was 3.9 (1.0–7.0) cm in group C and 3.7 (1.0–8.0) cm in group A (p = 0.5). Deformity parameters were corrected to satisfaction in all but 3 patients, who needed further surgery for complete deformity correction. However, minor residual deformity was common in one-third of the patients. The mean lengthening index was 2.2 (0.8–10) months/cm in group C and 2.0 (0.8–6) months/cm in group A (p = 0.7). Isolated analysis of all tibial and femoral lengthenings showed similar lengthening indices between groups. Complication rates and the need for secondary surgery were much greater in the group with congenital deformities. Interpretation — The TSF is an excellent tool for the correction of complex deformities in children. There were similar lengthening indices in the 2 groups. However, congenital deformities showed a high rate of complications, and should therefore be addressed with care.

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society. Cite this article: Nijhuis WH, Eastwood DM, Allgrove J, Hvid I, Weinans HH, Bank RA, Sakkers RJ. Current concepts in osteogenesis imperfecta: bone structure, biomechanics and medical management.

Distraction osteogenesis biologically resembles fracture healing with distinctive characteristics notably in the distraction phase of osteogenesis. In the latency phase of bone lengthening, like in the inflammatory phase of fracture repair, interleukines are released and act with growth factors released from platelets in the local haematoma, leading to attraction, proliferation and differentiation of mesenchymal stem cells into osteoblasts and other differentiated mesenchymal cells. These in turn produce matrix, collagen fibers and growth factors. A callus containing cells, collagen fibers, osteoid and cartilage matrix is formed. Provided stable fixation, distraction will trigger intramembranous bone formation. As distraction proceeds, the distraction gap develops five distinctive zones with unmineralized bone in the middle, remodelling bone peripherally, and mineralizing bone in between. During consolidation, the high concentration of anabolic growth factors in the regenerate diminishes with time as remodelling takes over to form mature cortical and cancellous bone. Systemic disease, congenital bone deficiencies, medications and substance abuse can influence the quality and quantity of regenerate bone, usually in a negative way. The regenerate bone can be manipulated when needed by using injection of mesenchymal stem cells and platelets, growth factors (BMP-2 and -7), and systemic medications (bisphosphonates and parathyroid hormone). Growth factors and systemic anabolic and antiresorptive drugs are prescribed on special indications, while distraction osteogenesis is not an authorized indication. To some extent, however, these compounds can be used off-label. Use in children presents special problems since growth factors and specific anabolic medications may involve a risk of inducing cancer.

Objective: Bioabsorbable barrier membranes placed over alveolar ridge bone defects are routinely used in dental surgery to promote bone formation. Combining these osteoconductive membranes with osteoinductive Bone Morphogenetic Proteins could prove useful in long bone fracture treatment. The hypothesis was tested in a clinically relevant model of compromised healing. Methods: Four groups of 8 rabbits underwent unilateral mid-tibial osteotomy, excision of periosteum and endosteum, and plate fixation. One group had rhBMP-2 deposited between the bone ends and Membrane wrapped around the osteotomy, the second group had Membrane wrapped around the osteotomy, the third group had rhBMP-2 placed between the bone ends, and the fourth group received no additional treatment. Results: After 7 weeks, callus size and blood flow were significantly higher in the Membrane+rhBMP-2 group than in the rhBMP-2 treated group, but torsion to failure test showed no significant difference. Membrane treatment and no treatment led to non-union. Conclusion: Absorbable barrier membrane combined with rhBMP-2 enhances bone formation, but has no advantage to rhBMP-2 alone. Membrane alone wrapped around the osteotomy was unable to prevent non-union formation.

This study investigated microarchitectural, mechanical, collagen and mineral properties of normal adolescent cancellous bone, and compared them with adult and aging cancellous bone, to obtain more insight into the subchondral bone adaptations during development and growth. Twenty-three human proximal tibiae were harvested and divided into 3 groups according to their ages: adolescence (9 to 17 years, n=6), young adult (18 to 24 years, n=9), and adult (25 to 30 years, n=8). Twelve cubic cancellous bone samples with dimensions of 8×8×8 mm(3) were produced from each tibia, 6 from each medial and lateral condyle. These samples were micro-CT scanned (vivaCT 40, Scanco Medical AG, Switzerland) resulting in cubic voxel sizes of 10.5*10.5*10.5 μm(3). Microarchitectural properties were calculated. The samples were then tested in compression followed by collagen and mineral determination. Interestingly, the adolescent cancellous bone had similar bone volume fraction (BV/TV), structure type (plate, rod or mixtures), and connectivity (3-D trabecular networks) as the adult cancellous bone. The adolescent cancellous bone had significantly lower bone surface density (bone surface per total volume of specimen) but higher collagen concentration (collagen weight per dry weight of specimen) than the adult cancellous bone; and significant greater trabecular separation (mean distance between trabeculae), significant lower trabecular number (number of trabeculae per volume), tissue density (dry weight per volume of bone matrix excluding marrow space) and mineral concentration (ash weight per dry weight of specimen) than the young adult and adult cancellous bones. Despite these differences, ultimate stress and failure energy were not significantly different among the three groups, only the Young's modulus in anterior-posterior direction was significantly lower in adolescence. Apparent density appears to be the single best predictor of mechanical properties. In conclusion, adolescent cancellous bone has similar bone volume fraction, structure type, and connectivity as the young adult and adult cancellous bones, and significant lower tissue density, bone surface density and mineral concentration but higher collagen concentration than in the young adult and adult bone. Despite these differences, the mechanical properties did not show significant difference among the three groups except less stiffness in anterior-posterior direction in the adolescents.

We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period, four groups received twice-weekly subcutaneous injections of alendronate (ALN) in two doses: two groups received 10 microg/kg and two groups received 50 microg/kg. The two control groups received vehicle. After 9 weeks, one 10 microg/kg ALN group, one 50 microg/kg ALN group, and one control group were killed. The remaining three groups (17-week groups) were left for an additional 8 weeks, receiving the same treatment regimen before death. The left proximal tibiae were scanned by micro-computed tomography to quantify the microarchitecture of subchondral bone, followed by mechanical testing and determination of collagen and mineral. The control groups had typical OA-related cartilage degeneration at 9 and 17 weeks, whereas the 50 microg/kg ALN group had even worse degeneration in the medial condyle. It is unclear whether there is a direct or a secondary effect of ALN on the cartilage. The 9-week ALN group had significantly greater subchondral plate thickness. The 9- and 17-week groups had similar changes of cancellous bone microarchitecture, with greater volume fraction and connectivity and an extremely plate-like structure. The 9-week ALN group had greater bone mineral concentration, and the 17-week ALN group had reduced collagen concentration and greater mineral concentration. Treatment with ALN did not significantly change the mechanical properties of the cancellous bone.

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model. Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.

Summary Introduction: Identification of patients at risk of developing non-union and institution of procedures preventing non-union could be attractive in routine fracture management. We investigated whether recombinant human bone morphogenetic protein (rhBMP-2) delivered in a hyaluronic acid carrier could prevent non-union development in an experimental non-union model, which simulates the clinical situation of open mid-tibial fractures. Methods: Sixteen rabbits underwent a standard non-union operation comprising mid-tibial osteotomy, excision of periosteum and endosteum, and plate fixation. Before closure of the wound eight rabbits received interfragmentary deposition of 200 μg rhBMP-2 delivered in a hyaluronan gel carrier, and eight rabbits received gel carrier alone. Results: After 7 weeks, torsional failure moment of the osteotomy and energy absorbed at failure, macroscopic and radiographic appearance, callus area, and interfragmentary bone volume fraction confirmed that rhBMP-2 delivery significantly improved bone healing. Blood flow at the osteotomy site, measured using radiolabelled microspheres, was not higher in the united osteotomies than in non-united osteotomies. Discussion: rhBMP-2 delivered in a hyaluronic acid carrier-induced formation of competent bone in an experimental model of compromised healing. We, therefore, propose interfragmentary deposition of rhBMP-2 delivered in a hyaluronic acid carrier to patients encountering fractures at risk of non-union or delayed union.

Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro-computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage.

Introduction: Therapeutic angiogenesis, a novel concept in tissue engineering, is neo-formation of blood vessels in a tissue upon delivery of an angiogenic growth factor to the tissue. We hypothesised that therapeutic angiogenesis could enhance bone formation and challenged the hypothesis in an experimental model of distraction osteogenesis. Methods: Rabbits, divided into three equal groups of 12, had their right tibia lengthened by distraction osteogenesis. A mini-osmotic pump delivered to the osteotomy gap either recombinant human vascular endothelial growth factor (VEGF), VEGF-inhibitor, or vehicle alone during the latency and distraction phase. After consolidation, we assessed bone blood flow by radioactive microsphere entrapment, measured torsional stiffness and bone mineral content, and did histomorphometry. Results: VEGF and VEGF-inhibitor treatment failed to influence bone blood flow, torsional stiffness, bone mineral content and histomorphometric indices of the bone regenerate. However, VEGF treatment increased the blood flow in bone of the distracted limb and VEGF-inhibitor treatment decreased bone blood flow. Conclusion: The regenerate was unresponsive to VEGF and VEGF-inhibitor treatment in contrast to the neighbouring bone, which implies different biological properties of the vasculature in native and regenerating bone. VEGF is not recommended for enhancement of bone formation in this setting.

The bisphosphonate, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. It has been used clinically for the treatment of osteoporosis and has also recently been used to reduce osteolysis around prostheses in a canine revision model of implant loosening (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral proximal humeri. These specimens were scanned using a high-resolution microcomputed tomography (micro-CT) system. From accurate data sets, three-dimensional microstructural properties were calculated and physical and mechanical properties were determined. Treatment with alendronate increased bone volume fraction by 9.5%, 7.7%, 7.4%, and 18.4%, respectively, in L-1, L-2, humeral greater tuberosity, and humeral head trabecular bone. In the lumbar vertebrae, the alendronate-treated trabeculae were thicker and lower in bone surface-to-volume ratio. In the greater tuberosity, the alendronate-treated trabeculae were thicker, lower in bone surface-to-volume ratio, and less anisotropic. In the humeral head, the alendronate-treated trabeculae were thicker, less anisotropic, lower in surface density, and showed decreased trabecular separation. Alendronate significantly increased apparent density and collagen density in the lumbar vertebrae and humeral heads, and significantly decreased collagen concentration in the vertebrae. In the lumbar vertebrae, Young's modulus in the cephalocaudal direction, ultimate stress, and failure energy were significantly increased in the alendronate-treated group. The changes in mechanical properties in the humeral head trabecular bone were similar to those seen in the lumbar vertebrae. Our results demonstrate that alendronate increases the mechanical properties of healthy canine trabecular bone after short-term treatment. The physical and microstructural changes of trabecular bone are consistent with the significantly increased mechanical properties.

The purpose of this study was to develop a method for simultaneous measurement of the mechanical properties of articular cartilage and underlying trabecular bone. Cylindrical bone-cartilage specimens from human cadaver knees were tested under non-destructive axial compression. The specimens were mounted in a cage by three screws fixed to the subchondral bone plate to create a reference plane between the cartilage and the bone. Each test was carried out as a single test cycle between a 0.12 MPa (4N) pre-stress and 0.5 per cent bone strain. Twenty conditioning cycles were performed prior to each test cycle. In order to determine the reproducibility of the test method, the test procedure was repeated after turning the cage through 90°. The specimens were then kept at + 5°C for 24 hours, and the procedure was repeated. The normalized stiffness and energy absorptive properties were calculated from each test cycle. No significant difference was found between the results obtained on the first and on the second day. Both days the stiffness of cartilage was significantly larger during the second test, indicating that 20 conditioning cycles may not provide a viscoelastic steady state.

Survivorship analysis was used in the evaluation of 348 consecutive primary total condylar knee arthroplasties (total knee arthroplasties) performed on 253 patients in a 27-month period, with a maximum follow-up period of 12 years. The diagnosis was osteoarthrosis in 184 cases and rheumatoid arthritis in 164 cases. Ten patients (10 total knee arthroplasties) were lost to follow-up evaluation. The endpoint was defined as prosthesis not in situ. The variables considered were age, sex, body mass index, and diagnosis. The overall cumulative survival rate was 92%. The survival rate of the osteoarthrosis group was significantly higher (97%) than that of the rheumatoid arthritis group (87%). None of the other variables affected survival rate significantly.

We have reviewed at an average period of ten years the results of 71 consecutive primary arthroplasties with the Insall-Burstein total condylar knee prosthesis in patients with rheumatoid arthritis. Their mean age at surgery was 52 years (24 to 72). At follow-up the overall results (Hospital for Special Surgery knee rating score) were excellent or good in 77%, fair in 11% and poor in 11%. There was residual pain in only 5% of patients with prostheses in situ; 58% could walk more than 500 m, and the median range of motion was 108 degrees. Eight knees had been revised. Five underwent arthrodesis because of deep infection and three needed revision arthroplasty for mechanical loosening. The crude survival rate of the arthroplasties was 89%. The presence of radiolucency around the tibial component correlated significantly with the severity of residual pain.

We report 144 femoral shaft fractures (FSF) in 138 children less than 15 years old. The boy/girl ratio was 2.8:1. The incidence rate was 28 per 100,000 child-years. Young children (less than 3 years) had the highest incidence rates. The most common etiology was trauma due to traffic accidents (43.1%) and falls (42.2%). Falling off bicycles contributed to 4.9%, direct trauma to 3.5%, and jamming to 5.6% of fractures. Involvement of children in traffic accidents and the number of FSFs due to traffic trauma fell significantly during the study period. The resource consumption of FSF was very high compared to other childhood fractures. The mean length of stay for FSF was almost three times that of all other patients seen in the emergency unit. Language: en

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens was studied by non-destructive uniaxial compression to 0.4% strain using cylindrical specimens with different sizes and length-to-diameter ratios, and by comparing cubic and cylindrical specimens with the same cross-sectional area. Both the length and the cross-sectional area of the specimen had a highly significant influence on the mechanical behaviour (p less than 0.0001). Within the actual range of length (2.75-11.0 mm) the normalized stiffness (Young's modulus) was related nearly linearly to the specimen length. This dependency on specimen length is suggested to be caused mainly by structural disintegrity of the trabecular specimens near the surface. The normalized stiffness (Young's modulus) was also positively correlated to the cross-sectional area. This dependency on cross-sectional area is probably due to friction-induced stress inhomogeneity at the platen-specimen interface. A cube with side length 6.5 mm or a cylindrical specimen with 7.5 mm diameter and 6.5 mm length are suggested as standard specimens for comparative studies on trabecular bone mechanics.

Udgivelsesdato: 2009-Dec BACKGROUND AND PURPOSE: Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans. METHODS: 72 New Zealand White rabbits underwent tibial mid-diaphyseal osteotomy and the callus was distracted 1 mm/day for 10 days. The rabbits were divided into 3 groups, which received injections of PTH 25 microg/kg/day for 30 days, saline for 10 days and PTH 25 microg/kg/day for 20 days, or saline for 30 days. At the end of the study, the rabbits were killed and the bone density was evaluated with DEXA. The mechanical bone strength was determined by use of a 3-point bending test. RESULTS: In the 2 PTH-treated groups the regenerate callus ultimate load was 33% and 30% higher, absorbed energy was 100% and 65% higher, BMC was 61% and 60% higher, and callus tissue volume was 179% and 197% higher than for the control group. INTERPRETATION: We found that treatment with PTH during distraction osteogenesis resulted in substantially higher mineralized tissue volume, mineral content, and bending strength. This suggests that treatment with PTH may benefit new bone formation during distraction osteogenesis and could form a basis for clinical application of this therapy in humans.

The effect of strain rate (e) and apparent density (ϱ) on stiffness (E), strength (σu), and ultimate strain (eu) was studied in 60 human trabecular bone specimens from the proximal tibia. Testing was performed by uniaxial compression to 5% specimen strain. Six different strain rates were used: 0.0001, 0.001, 0.01, 0.1, 1, and 10 s−1. Apparent density ranged between 0.23 and 0.59 g cm−3. Linear and non-linear regression analyses using strength, stiffness and ultimate strain as dependent variables (Y) and strain rate and apparent density as independent variables were performed using the following models: Y = aϱ b e c , Y = ϱ b (a+c e ; Y=(a+bϱ) e c , Y=aϱ 2 e c , E=aϱ 3 e c . The variations of strength and stiffness were explained equally well by the linear and the power function relationship to strain rate. The exponent was 0.07 in the power function relationship between strength and strain rate and 0.05 between stiffness and strain rate. The variation of ultimate strain was explained best using a power function relationship to strain rate (exponent =0.03). The variation of strength and stiffness was explained equally well by the linear, power function and quadratic relationship to apparent density. The cubic relationship between stiffness and apparent density showed a less good fit. Ultimate strain varied independently of apparent density.

Udgivelsesdato: 2009 We investigated if injectable calcium phosphate cement improves primary stability in open-wedge high-tibial osteotomy. A 10 mm open-wedge osteotomy was performed on eight pairs of preserved cadaver tibiae and seven pairs of composite (Sawbone) left tibiae. Osteosynthesis was performed with the Dynafix plate system. The gap resulting from surgery either was filled with 15 g injectable calcium phosphate cement in half the bones or was left untreated. The composite tibiae were loaded at a ramp speed of 20 mm/min up to 20 kN. The cadaver tibiae were exposed to 100 cycles with a maximum compressive force of 2,250 N. After 100 cycles of loading with 2,250 N, the final loaded displacement was 1.2 mm for the cadaver tibiae treated with injectable calcium phosphate cement as compared with 3.6 mm for the empty defects (P = 0.028). All the seven empty defect composite specimens failed prior to 20 kN (median 2.8 kN) as compared with five of the injectable calcium phosphate cement specimens (median 17 kN) (P = 0.005). The injection of injectable calcium phosphate cement following open-wedge osteotomy of the proximal tibia increases the initial stability of the bone as measured by load-to-failure and displacement after cyclic loading. Clinical studies are ongoing to investigate whether injectable calcium phosphate cement also has clinical advantage on wedge healing and stability.

This issue of Acta presents two articles dealing with (1) early diagnosis of neonatal hip instability (NHI) (Finne et al. 2008), and (2) the associated risk of total hip replacement (THR) in young ...

The overall purpose of the study is to determine the effects of parathyroid hormone (PTH) (1-34) on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening in rabbits. Additionally the aim of the pilot study is to titrate the optimal dose of PTH for distraction osteogenesis treatment in rabbits' tibial lengthening model.A total of 18 rabbits underwent right tibia lengthening by callus distraction. Lengthening was started 5 days postoperatively 1 mm/day for a 10-day period and consolidation of 20 days followed. Rabbits were divided into three groups: group I received PTH (1-34) treatment at a dose of 5 microg/kg/day, group II received treatment with PTH (1-34) at a dose of 25 microg/kg/day; group III rabbits were treated with saline. After euthanasia, tibiae of both legs were dissected free, kept frozen and underwent x-ray analysis, dual x-ray absorptiometry-scanning, microcomputed tomography scanning and three-dimensional evaluation and mechanical test followed.Over all, during distraction osteogenesis in a new regenerated bone, PTH (1-34) treatment with two different doses of 5 microg/kg/day and 25 microg/kg/day increased callus cross-sectional area, callus bone mineral density and bone mineral content, bone volume density; dramatically increased trabecular number with slight increase in trabecular thickness, whereas decreased trabecular separation, bone surface density and decreased degree of anisotropy when compared to control group animals.PTH (1-34) treatment improved mineralization, structural indices of regenerated distracted rabbits' tibiae, whereas treatment at a dose of 25 microg/kg/day PTH (1-34) was significantly more effective than 5 microg/kg/day PTH(1-34) dose treatment when compared to control group. Bigger dose has been chosen for the main study.

Distraction osteogenesis can be used for the treatment of osteomyelitis and nonunion, conditions thought to benefit from increased blood flow in the bone tissue of the distracted limb. We have questioned whether such an increase occurs, and investigated the spatial distribution of bone blood flow after distraction osteogenesis.The tibiae of 8 rabbits were lengthened 10 mm by a standard midtibial distraction osteogenesis procedure. 2 weeks into the consolidation phase, the bone and soft tissue blood flow of the distracted and the contralateral extremity were measured using radioactive microspheres.The absolute bone blood flow of the distracted tibia was 4% lower than that of the non-distracted side, representing a 41% decrease in the proximal metaphysis, a smaller decrease in the proximal epiphysis, distal metaphysis and distal epiphysis, and an increase in the diaphysis.Mid-tibial distraction osteogenesis redistributed the bone blood flow of the distracted tibia, but absolute tibial blood flow did not increase. Our results do not confirm previous research in this field.

Parathyroid hormone naturally secreted by the parathyroid glands is a potent anabolic agent for bone. Parathyroid hormone is primarily thought of as a catabolic protein involved in the physiologic release of calcium from bone. Whereas during recent years, a number of animal studies and clinical trials have demonstrated that intermittent parathyroid hormone administration induces anabolic effects on both cancellous and cortical bone, enhances bone mass and increases mechanical strength of the bones. Most of the studies, both animal and human, have addressed the treatment of osteoporosis and parathyroid hormone represents an important new advance in the therapy of osteoporosis. Few studies have investigated the effect of intermittent parathyroid hormone treatment in the field of orthopedics on fracture healing and fixation of orthopedic implants. The results of those studies indicated an enhancement of fracture healing, faster bone repair and better fixation of the implant. Recently there were few animal studies started to investigate the effects of parathyroid hormone treatment on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening. Distraction osteogenesis is a technique for bone lengthening that is widely used clinically and experimentally. Newly forming bone during distraction osteogenesis is expected to be an appropriate pattern for parathyroid hormone anabolic effect. Preclinical studies as well as clinical trials suggest that parathyroid hormone might be useful as a stimulator of bone formation whereas a lot of questions regarding parathyroid hormone therapy remain unanswered and require further experimental studies and investigations.

Hyaluronan (HA) has received increasing interest as a potential agent in therapeutic intervention in osteoarthrosis (OA). HA has been shown to reduce arthritic lesions in experimental animal models of articular cartilage injury. This study was to investigate the effects of high molecular weight HA intra-articular injection on subchondral bone tissues. Fifty-six male guinea pigs were randomly divided into 5 groups. During the initial 2.5-month period, three groups received intra-articular injection of HA 0.4 mg/kg/week for 5 weeks in both knee joints. Two control groups received vehicle. After 2.5 months, one HA group and one control group were sacrificed. The remaining 3 groups (5.5-month groups) were left for an additional 3 months before sacrifice during which time one HA group received additional 5 weeks injections, one HA group received no more injections, and the control group received vehicle. The left tibiae were harvested and micro-CT scanned to quantify three-dimensional microarchitecture of subchondral bone plate, cancellous bone and cortical bone, followed by mechanical testing and collagen and mineral determinations. All HA-treated groups had almost normal cartilage, whereas the control groups had typical OA-related cartilage degradation. In the 2.5-month group, HA resulted in significantly decreased subchondral plate volume fraction and thickness and HA-treated cancellous bone had significantly lower bone volume fraction, and typical rod-like structure. After 5.5 months, these changes were more pronounced, with an additional marked decrease in connectivity and bone surface density. HA-treated cortical bone had significantly greater volume fraction at both observation times. HA groups had greater bone mineral concentration and reduced collagen to mineral ratio with similar mechanical properties of cancellous bone but less stiff cortical bone. The effects of HA on cartilage and subchondral bone were maintained when treatment was discontinued. In summary, HA effectively protects against cartilage degeneration, decreases subchondral bone density and thickness, changes trabecular structure toward rod-like, so that subchondral bone becomes more compliant and thereby reduces cartilage stress during impact loading. HA preserved cancellous bone mechanical properties by increasing bone mineralization. Early HA administration is effective for intervention of OA initiation and progression, and short-term early HA treatment is sufficient to maintain treatment effects.

We examined the effects of one-year high-dose bisphosphonates (risedronate 0.5 mg/kg/day or alendronate 1.0 mg/kg/day) on the three-dimensional (3-D) microstructural and mechanical properties of canine cancellous bone. A high-resolution micro-CT scanner was used to scan cubic specimens produced from the first lumbar vertebrae. Microstructural properties of the specimens were calculated directly from the 3-D datasets and the mechanical properties of the specimens were determined. Our data demonstrate significant microarchitectural changes in the bisphosphonate-treated cancellous bone that was typically plate-like, denser, with thicker and more trabeculae compared with those of the controls. Consistent with architectural changes, the Young's moduli of cancellous bone increased in all three directions with the greatest increase in primary axial loading (cephalo-caudal) direction after treatment. Our results suggest a bone remodeling-adaptation mechanism stimulated by bisphosphonates that increases bone volume fraction, thickens trabeculae, changes trabeculae towards more plate-like, and increases mechanical properties. The secondary degree of anisotropy contributed significantly to the explained variance in bone strength, and the primary or tertiary degree of anisotropy improved the explanation of variances for Young's moduli, i.e., 79% of strength variances or 74-83% of modulus variances could be explained by the combined anisotropy and bone volume fraction. These significant improvements of cancellous bone architecture provide a rationale for the clinical observation that fracture risk decreased by 50% in the first year of bisphosphonate therapy with only a 5% increase in bone mineral density. We conclude that bisphosphonates enhance mechanical properties and reduce fracture risk by improving architectural anisotropy of cancellous bone 3-D microarchitecture.

Previous studies have shown that low-density, rod-like trabecular structures develop in regions of low stress, whereas high-density, plate-like trabecular structures are found in regions of high stress. This phenomenon suggests that there may be a close relationship between the type of trabecular structure and mechanical properties. In this study, 160 cancellous bone specimens were produced from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The specimens underwent micro-CT and the microstructural properties were calculated using unbiased three-dimensional methods. The specimens were tested to determine the mechanical properties and the physical/compositional properties were evaluated. The type of structure together with anisotropy correlated well with Young's modulus of human tibial cancellous bone. The plate-like structure reflected high mechanical stress and the rod-like structure low mechanical stress. There was a strong correlation between the type of trabecular structure and the bone-volume fraction. The most effective microstructural properties for predicting the mechanical properties of cancellous bone seem to differ with age.

Children's fractures are a challenge to the treatment system, in that 17,000 children are treated in Denmark each year. The true burden on patients and society is unknown. It is estimated that 1000 new-born infants are treated for hip instability in Denmark per year, and 30 are diagnosed late. Ultrasound scanning is recommended for secondary screening and selective screening of children at risk. Identification of acetabular dysplasia followed by surgical correction could be an important prophylactic measure, with a potential reduction in expenses to society. To some extent, congenital clubfoot is hereditary. Environmental factors are important, maternal smoking being one. Early operative treatment yields good results. There is a need for prospective registration. Perthes' disease is an idiopathic necrosis of the capital femoral epiphysis. Passive smoking is a significant factor. A young age (7 years) and limited necrosis carry a good prognosis, and active treatment can improve the prognosis for the other patients.

A thorough understanding of the microstructure of cancellous bone is crucial for diagnosis, prophylaxis, and treatment of age-related skeletal diseases. Until now, little has been known about age-related variations in the microstructure of peripheral cancellous bone. This study quantified age-related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16–85 years. These specimens were micro-computed tomography (micro-CT) scanned, and microstructural properties were determined. The specimens were then tested in compression to obtain Young's modulus. The degree of anisotropy, mean marrow space volume, and bone surface-to-volume ratio increased significantly with age. Bone volume fraction, mean trabecular volume, and bone surface density decreased significantly with age. Connectivity did not have a general relationship with age. Bone volume fraction together with anisotropy best predicted Young's modulus. Age-related changes in the microstructural properties had the same trends for both medial and lateral condyles of the tibia. The observed increase of anisotropy and constant connectivity suggest a bone remodeling mechanism that may reorient trabecular volume orientation in aging tibial cancellous bone. The aging trabeculae align more strongly to the primary direction – parallel to the tibial longitudinal loading axis.

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods. Both thickness and spacing calculated using the plate model were well correlated to the direct three-dimensional measures (r(2) = 0. 77-0.92). The correlation between trabecular number and connectivity density varied greatly (r(2) = 0.41-0.94). Whereas trabecular thickness was consistently underestimated using the plate model, trabecular spacing was underestimated at low volume fractions and overestimated at high volume fractions. Use of the plate model resulted in a volume-dependent bias in measures of thickness and spacing (p < 0.001). This was a result of the fact that samples of low volume fraction were much more "rod-like" than those of the higher volume fraction. Our findings indicate that the plate model provides biased results, especially when populations with different volume fractions are compared. Therefore, we recommend direct thickness measures when three-dimensional data sets are available.

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density.

Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial) cancellous bone. In this study, 160 human proximal tibial cancellous bone specimens from 40 normal donors, aged 16 to 85 years, were collected. These specimens were micro-computed tomography (micro-CT) scanned, then the micro-CT images were segmented using optimal thresholds. From accurate 3-D data sets, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allows quantification of structure model type, such as plate, rod objects, or mixture of plates or rods. Trabecular thickness is calculated directly from 3-D images, which is especially important for an a priori unknown or changing structure. Furthermore, 2-D trabecular thickness was also calculated based on the plate model. Our results showed that structure model type changed towards more rod-like in the elderly, and that trabecular thickness declined significantly with age. These changes become significant after 80 years of age for human tibial cancellous bone, whereas both properties seem to remain relatively unchanged between 20 and 80 years. Although a fairly close relationship was seen between 3-D trabecular thickness and 2-D trabecular thickness, real 3-D trabecular thickness was significantly underestimated using 2-D method.

Cylindrical human tibial cartilage-bone unit specimens were removed from 9 early-stage medial osteoarthrotic (OA) tibiae (mean age 74 years) and 10 normal age-matched tibiae (mean age 73 years). These specimens were divided into 4 groups: OA, lateral comparison, medial age-matched, and lateral age-matched and were tested to 0.5% bone strain with a novel technique to obtain the stiffnesses of both cartilage and bone simultaneously. We found a pronounced reduction in the stiffnesses of OA cartilage and subchondral bone when compared with the medial age-matched group. OA cartilage was significantly thinner than that of the lateral comparison and the medial age-matched control groups. However, this reduction in thickness was not correlated with the reduction in stiffness for OA cartilage. The stiffnesses did not correlate between OA cartilage and bone, whereas the stiffness relationships between cartilage and bone remained significant in the three control groups. Our findings suggest that both cartilage and bone in early-stage OA are mechanically inferior to normal, and that OA cartilage and bone have lost their unit function to mechanical loading.

We investigated changes in periosteal insulin-like growth factor I (IGF-I) during tibial lengthening. In 37 rabbits, an osteotomy of the right middle tibia was made and fixed by a unilateral external fixator. The rabbits were randomized into 6 groups: the tibiae were distracted at 0.5 mm/day up to 4 weeks and the animals killed after 2 weeks, 4 weeks or 6 weeks, for each period there was a control group with no distraction. Periosteal IGF-I was measured by radioimmunoassay and bone formation was quantified by CT scanning. During bone lengthening, CT showed moderate bone formation, while IGF-I was increased. When lengthening was stopped, IGF-I returned to a basal level, and CT scanning showed considerable bone formation. Our study suggests that IGF-I plays a role in an early stage of bone formation.