Peri-implant osteogenesis in health and osteoporosis.

Osteoporosis is a major health problem characterized by compromised bone strength that predisposes patients to an increased risk of fracture. Osteoporotic patients differ from normal subjects in bone mineral composition, bone mineral content, and crystallinity. Poor bone quality in patients with osteoporosis presents the surgeon with difficult treatment decisions. Much effort has been expended on improving therapies that are expected to preserve bone mass and thus decrease fracture risk. Manipulation of both the local fracture environment in terms of application of growth factors, scaffolds and mesenchymal cells, and systemic administration of agents promoting bone formation and bone strength has been considered as a treatment option from which promising results have recently been reported. Surprisingly, less importance has been given to investigating fracture healing in osteoporosis. Fracture healing is a complex process of bone regeneration, involving a well-orchestrated series of biological events that follow a definable temporal and spatial sequence that may be affected by both biological factors, such as age and osteoporosis, and mechanical factors such as stability of the osteosynthesis. Current studies mainly focus on preventing osteoporotic fractures. In recent years, the literature has provided evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new osteoporosis treatments on fracture healing. However, the mechanics of this influence of osteoporosis on fracture healing have not yet been clarified and clinical evidence is still lacking.

Fracture healing in osteoporotic fractures: is it really different? A basic science perspective.

Demographic changes in the age structure of occidental populations are giving rise to osteoporosis and associated fractures, which are becoming a major public health burden. Various animal models have been established and used to investigate the pathogenesis of osteoporosis and to facilitate the preclinical testing of new treatment options such as antiresorptive drugs. Although osteoporosis can be induced in animals, spontaneous fractures without adequate trauma were only found in nonhuman primates. An animal model designed to investigate new ways to treat fractures of osteoporotic bone has to fulfill requirements that are very different from those of pharmacological testing. The aspects of major interest in orthopedic applications are bone fragility, efficacy of implant fixation and bone healing. Existing animal models for osteoporosis were critically reviewed focusing on these aspects. The advantages and disadvantages of the models with regard to their application in the testing of new fracture-fixation devices or biological approaches to stimulate bone healing are discussed. Ovariectomy alone does not cause the bone loss seen in osteoporotic human patients. New models to simulate fracture of osteoporotic bone need to be explored and used to address the specific aims of an experiment.

Animal models for fracture treatment in osteoporosis.

Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model.

Aim In order to assess the effect of osteoporosis on healing time, the files of 165 patients with femoral shaft fractures that were treated in our institution with locked-reamed intramedullary nailing were retrospectively reviewed. Patients and methods Patients with open fractures, pathological fractures, revision surgery, severe brain injuries and prolonged ITU stay were excluded. In all patients the Singh-index score for osteoporosis and the canal bone ratio (CBR) were assigned. Sixty-six patients fulfilled the inclusion criteria. Patients were divided into two groups; group A (29 patients) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (37 patients) of patients between 18 and 40 years old with no signs of osteoporosis. Results In all group A patients Singh score ≤4 and CBR > 0.50 were assigned, suggesting the presence of osteoporosis, whereas all group B patients were assigned with Singh score ≥5 and CBR  P  = 0.02. Conclusions Fracture healing of nailed femoral diaphyseal fractures is significantly delayed in older osteoporotic patients. Further studies are required to clarify the exact impact of osteoporosis in the whole healing process.

The influence of osteoporosis in femoral fracture healing time.

Objective: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. Methods: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. Results: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P 0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P 0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. Conclusions: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.

Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model.

Objective To evaluate the effect of osteoporosis on fracture healing through observing the histomorphological changes, bone mineral density of callus and expression and distribution of transforming growth factor beta 1 (TGF-beta1), basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in ovariectomized rats. Methods Sixty female Sprague-Dawley rats (aged 12 weeks and weighing 235 g on average) were randomly divided into an ovariectomized (OVX) group (n=30) and a sham-operated (SO) group (n=30). Ovariectomy was performed in the OVX rats and same incision was made in the SO rats. Three months later, fracture of femoral shaft was made on all the rats. Then they were killed at different time points. Callus formation was observed with histological and immunohistochemical methods. Results A reduction in callus and bone mineral density in the healing femur and a decrease of osteoblasts expressing TGF-beta1 near the bone trabecula were observed in the OVX rats 3-4 weeks after fracture. Histomorphological analysis revealed a higher content of soft callus in the OVX rats than that in the SO rats. Immunohistochemistry results showed that no remarkable difference in expression and distribution of BMP-2 and bFGF between the OVX and SO groups was found. Conclusions Osteoporosis influences the quantity and quality of callus during the early period of fracture healing. The effect of osteoporosis on fracture healing has no relationship with the expression of BMP-2 or bFGF. The decreased expression of TGF-beta1 in osteoblasts may cause a decrease in quality of fracture healing after osteoporosis.

Early period of fracture healing in ovariectomized rats.

OBJECTIVE To evaluate the influence of osteoporosis on fracture healing. METHODS Eighty-four 4 months old female Sprague-Dawley rats were randomly divided into osteoporosis (OP) group and sham operation (SO) group, 42 in each. Rats in OP group were performed ovariectomy operation while those in SO group with sham operation. When osteoporosis formed 10 weeks after ovariectomy, midshaft tibia fracture model was established. Tibias were harvested 2 weeks (2 rats per group), 4 weeks (9 rats per group), 6 weeks (9 rats per group), 12 weeks (9 rats per group) and 18 weeks (7 rats per group) after fracture for bone mineral density (BMD), histomorphological and biomechanical evaluation. RESULTS Compared with the SO group: (1) Callus BMD was significantly lower about 12.8%, 18.0%, 17.0% in OP group 6, 12, 18 weeks after fracture, respectively (P < 0.05). (2) Callus failure load was significantly lower about 24.3%, 31.5%, 26.6%, 28.8% in OP group, and callus failure stress was also significantly lower about 23.9%, 33.6%, 19.1%, 24.9% in OP group 4, 6, 12, 18 weeks after fracture, respectively (P < 0.05). (3) In OP group, endochondral bone formation was delayed, more osteoclast cell could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. CONCLUSION Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporostic model. The impairment is considered to be the result of the combined effects of the prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.

Osteoporosis impairs fracture healing of tibia in a rat osteoporotic model

Objective: To dynamically monitor the bone mineral density (BMD) and the histomorphological changes during fracture healing in a rat femoral fracture model and to explore the role of dual energy X-ray absorptiometry (DEXA) in evaluating bone fracture healing. Methods: Sixty three-month-old female Sprague Dawley rats were used to establish right femoral fracture models. The BMD of the callus of the fractured right femur were scanned by DEXA at 2, 4, 6, 8, 10 and 12 weeks after operation, respectively. A light microscope was used to evaluate the callus of each rat at the same time. The corresponding segment of the left femur was taken as a control. Results: The BMD at the fractured site increased significantly during the process of facture healing, which shows an obvious healing trend. The callus BMDs were 29.5%, 48.3%, 85.3%, and 105.2% of the BMD of the control limb at 2, 4, 6 and 8 weeks after fracture, respectively. There was a significantly difference between the groups. A compatibility on time was found between the BMD and the histomorphological characteristics at the fractured site during the process of fracture healing. The fracture healing was almost completed at 8 weeks after fracture as assessed by its histomorphological characteristics when the callus BMD reached to 105.2% of the BMD of the control limb. The BMD of the distal metaphysis decreased until 12 weeks after fracture. Conclusions: DEXA can evaluate the mineralization of the callus during the facture healing process accurately and quantitatively and is more sensitive than plain radiography in detecting impaired bone unions, which indicates that it may play an important role in monitoring fracture healing.

Guang-feng Zhao

Papers

Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model.

Early period of fracture healing in ovariectomized rats.

Osteoporosis impairs fracture healing of tibia in a rat osteoporotic model

Role of dual energy X-ray absorptiometry in monitoring fracture healing in a rat femoral fracture model.