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Biomedical subjects

Ivan Hvid

Publications and source records attributed to Ivan Hvid.

11 recordsLinked to original sources

Surgery in hemophilia. The general view: patient selection, timing, and preoperative assessment.

Although often overlooked, the life of the patient with severe hemophilia is characterized by both intermittent and chronic pain. Bleeds into joints and muscles cause extensive pressure on sensory nerves and, following recurrent bleeds, joint destruction, and synovial reaction is accompanied by constant pains that are frequently mistaken for further bleeding. The orthopedic surgeon may break the vicious cycle of chronic synovitis by excising inflamed and hypertrophic synovium or severely damaged cartilage and adjacent bone ends, and implanting an artificial joint. Numerous technical solutions are now available and orthopedic surgery is increasingly on offer to those hemophilia patients who, since childhood, have been victims of insufficiently treated bleeds because no or limited treatment was available, and because the concept of prophylaxis had not yet been developed. Nonetheless, orthopedic surgery in patients with hemophilia requires much more effort and planning than surgery in non-hemophilic patients. In this overview, we will address issues related to surgery in hemophilic patients, as well as some practical issues related to the timing of surgery, preoperative testing, perioperative hemostasis, and patient rehabilitation.

Hemophilia A↗

Effects of parathyroid hormone on newly regenerated bone during distraction osteogenesis in a rabbit tibial lengthening model. A pilot study.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Absorptiometry, Photon↗

Recombinant human bone morphogenetic protein 2 enhances bone healing in an experimental model of fractures at risk of non-union.

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 microg 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.

Animals↗

Effects of hyaluronan on three-dimensional microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis.

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.

Animals↗

Mid-tibial distraction osteogenesis redistributes bone blood flow: a microsphere study in rabbits.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

Animals↗

Parathyroid hormone--possible future drug for orthopedic surgery.

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.

Animals↗

Effects of locally applied vascular endothelial growth factor (VEGF) and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis.

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.

Angiogenesis Inducing Agents↗

[Child orthopedics].

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.

Child↗

Age-related variations in the microstructure of human tibial cancellous bone.

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.

Adolescent↗

Mutual associations among microstructural, physical and mechanical properties of human cancellous bone.

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.

Adolescent↗