It has been reported that vitamin K can bind to steroid receptors to regulate gene transcription in osteoblast 3 , 4. In addition, vitamin K not only enhances bone formation, but also inhibits bone degradation 5 , 6. Vitamin K treatment can prevent bone loss and reduce the risk of fracture in women with postmenopausal osteoporosis 7 , 8. Injection of teriparatide increases the number of osteoblasts, activates osteoblast activity, promotes osteoblast differentiation, increases trabecular bone volume and strength, and effectively stimulates bone formation 9 , Clinical trials have shown that teriparatide injection can increase bone density and reduce fracture risk in women with postmenopausal osteoporosis 11 — Based on this, we hypothesized that vitamin K combined with teriparatide can promote bone formation and inhibit bone degradation, thereby improving bone metabolism.
In this study, vitamin K combined with teriparatide was used to treat osteoporosis induced by ovariectomy in rats. The effects of the combination therapy on bone mineral density, bone strength and bone metabolic parameters were evaluated. The rats were separately raised in an SPF grade animal compartment with free access to water and food. No significant difference in weight was found between the groups. Surgical incision was also made in the same position of rats in the sham group but ovariectomy was not performed. Rats in the other groups were fed with vitamin K-deficient feed supplemented with calcium 0.
Rats in the other groups were injected subcutaneously with an equal volume of normal saline. Detection of bone metabolism parameters and bone mineral density.
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Rats were sacrificed by cervical dislocation, bilateral femur was collected from each rat, and soft tissue was removed. Dual-energy X-ray absorptiometry was used to scan the right femur to detect the bone density of the middle part of the femur and the position 1. Lateral diameter of right femur was measured with a vernier caliper to calculate the area of the cross section of the midline of the femur. The three-point bending test was performed using a hydraulic servo fatigue testing machine Servopulser; Shimadzu, Kyoto, Japan.
The load-deformation curve was recorded, and elastic load, the maximum load and breaking load were calculated. The measuring range was the secondary cancellous bone 1—4 mm below the growth plate of metaphysis of proximal femur.
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Images were randomly selected from the left, middle and right of the sections and six images were captured for each specimen. The morphological parameters of bone tissue were analyzed using pathological image analysis software. Bone absorption parameters included number of osteoblast Ob , number of osteoblasts per unit area of bone trabecula, as well as surface area of osteoclast Oc , number of osteoclasts per unit area of bone trabecula.
SPSS Comparisons of indexes between the groups were performed using the Student's t-test. As shown in Fig. Bone metabolism indexes.
It is noteworthy that the bone mineral density of the VK group did not change significantly, and was slightly lower than that of the OVX group, the bone density of the TP group was higher than that of the OVX group. Bone intensity of femur. Similar to the results of bone density of femoral shaft, no significant differences in the biomechanical parameters elastic, maximum and fracture loads of the femoral shaft were found between all groups Fig.
Connective Tissue: Histophysiology, Biochemistry, Molecular Biology
Biomechanics of femoral metaphysis. A Maximum load of femoral metaphysis N. C Elastic load of femoral metaphysis N. Biomechanics of femoral shaft. A Maximum load of femoral shaft N. C Elastic load of femoral shaft N. Changes in the static, dynamic, and bone resorption parameters are shown in Fig. Bone histology parameters. In this study, ovariectomy was performed to construct a rat model of osteoporosis. Effects of vitamin K and teriparatide monotherapy and combination therapy on bone metabolic parameters, bone mineral density, biomechanics and bone histomorphology were compared.
Compared with monotherapy, vitamin K combined with teriparatide significantly increased the level of bone formation marker Gla-OC in serum and the number of osteoblasts.
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Results showed that the efficacy of vitamin K combined with teriparatide in the treatment of rats with osteoporosis is better than that of monotherapy. The combination treatment can promote bone formation by increasing the number of osteoblasts. Rats that underwent ovariectomy were usually used as an animal model of osteoporosis.
The model has good reproducibility, high bone turnover rate, accelerated bone formation and degradation, which can mimic postmenopausal osteoporosis in women caused by the lack of estrogen In this study, ovariectomy resulted in the loss of femoral metaphyseal minerals and decreased mechanical strength, but did not affect the bone density and mechanical strength of the femoral shaft. This is consistent with previous studies whereby ovarian resection led to loss of cancellous bone metaphyseal without affecting the cortical bone backbone In addition, the present study also found that ovariectomy increased the serum levels of Gla-OC and CTX-I, indicating accelerated bone turnover in rats with osteoporosis.
Following treatment with vitamin K, levels of Gla-OC were increased, CTX-I levels were decreased, the number of osteoblasts was increased, while the number of osteoclasts was decreased in rats with osteoporosis, indicating that vitamin K promotes bone formation and inhibits bone degradation, which is consistent with previous studies 5 , 6 , 18 , Teriparatide can increase the number of osteoblasts in bone trabecula and activate cell activity in rats with osteoporosis, thereby promoting bone formation and increasing cancellous bone mass 20 , The findings of this study showed that teriparatide was able to promote bone formation by increasing serum levels of Gla-OC and number of osteoblasts.
The mechanism of the effects of teriparatide on bone degradation remains unclear. Administration of teriparatide in ovariectomized rats did not alter the level of CTX-I, but increased the number of osteoclasts. Compared with vitamin K or teriparatide monotherapy, vitamin K combined with teriparatide significantly increased the serum levels of Gla-OC and the number of osteoblasts, indicating that vitamin K combined with teriparatide can promote bone formation. Following treatment with vitamin K, the serum CTX-I level was reduced and the number of osteoclasts was also reduced.
Compared with trepiparone monotherapy, vitamin K combined with teriparatide reduced the serum level of CTX-I and the number of osteoclasts. These results suggest that both vitamin K monotherapy and in combination with teriparatone can inhibit bone degradation. Additionally, the administration of teriparatide in rats with osteoporosis significantly increased bone density, maximum load and breaking load, which is consistent with previous studies 22 , By contrast, vitamin K can enhance fracture load, but cannot increase bone density Vitamin K mainly enhances bone strength by increasing Gla-OC levels and therefore does not affect bone density Compared to vitamin K monotherapy, vitamin K combined with teriparatide can significantly improve the bone density of femoral metaphysis.
Compared with teriparatide monotherapy, vitamin K combined with teriparatide did not significantly improve bone density. However, compared with vitamin K or teriparatide monotherapy, vitamin K combined with teriparatide significantly increased the maximum and breaking loads. These results suggest that vitamin K combined with teriparatide can improve bone density and strength.
Vitamin K monotherapy can reduce the femoral elastic load. In the 65 to 85 age group, the cost of treating such disorders is second only to the cost of cardiovascular disease treatment. Hip and upper thigh injuries are extremely costly, especially in the over 65 age group. Taking into account demographic trends, further cost increases can be expected in the coming years.
It is therefore crucial to find efficient treatment methods, and biomechanics is well placed to make major contributions to this effort. What kind of stress can bones and cartilage withstand? This is an important question for osteoporosis research as well as other areas. A group of biomechanics specialists at the University of Ulm is investigating fracture healing, particularly in osteoporotic bones.
Biomechanics at the University of Constance are investigating the load on bones during everyday movements and sports activities. The Constance researchers are carrying out comparative biomechanical analyses on the load and demands made on human phalanges, in particular in professional musicians and sports climbers who are exposed to a particularly strong load. Although too much strain is harmful, it is also known that the human body deteriorates if exposed to too little mechanical strain and as a result, is not able to maintain its normal functions.
Something that is easily understood in terms of muscles, is also valid on the molecular level. Mechanical influences affect biochemical processes; they can stimulate or inhibit them. This is not a new finding. As far back as the end of the 19 th century, the physician Julius Wolff from Berlin realised that external mechanical influences lead to tissue alterations. In , Wolff published a theory according to which bone remodels itself over time to become stronger and more resistant to the loads it is placed under. This theory is known as Wolff's law. Increasing knowledge about the metabolism and the molecular relationships have led to increasing insights into the details of what happens on the cellular level and below.
In the s, Swann et al. Implants have been shown to have a huge influence on bone remodelling, i. In recent years, the influence of mechanical forces on the metabolic activity and on the differentiation and proliferation of cells has been described in detail e. The "Molecular Biomechanics" group at the Heidelberg Institute for Theoretical Studies HITS is pursuing innovative approaches to investigate the mechanobiochemistry of blood coagulation and spider silk.
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