Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.
Animals ; Bone Regeneration/*drug effects ; Bone Substitutes/*therapeutic use ; Bone and Bones/*drug effects/pathology/physiopathology ; Ceramics/therapeutic use ; Diffusion of Innovation ; Fracture Healing/drug effects ; Humans ; Hydrogels ; Polymers/therapeutic use ; Regenerative Medicine/*trends ; Tissue Engineering/*trends ; Treatment Outcome

BACKGROUNDPrevious studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone. However, the effect of prostaglandin I2 (PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a study on fracture healing process in closed tibia fractures was designed.

METHODSThirty-six Sprague-Dawley male rats were randomized into two groups. On the first day, their right tibias were fractured by three-point bending technique. The study group (n = 18) received a single injection of 10 µg/kg iloprost for 5 days, while the control group (n = 18) received saline solution in the same way. On the 7th, 14th and 28th days following the fracture, six rats were sacrificed and their right legs were harvested in each group. The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al).

RESULTSOn the 7th day, the radiographic and histologic scores were equal. On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group, whereas radiographic total score was 11 and histologic total score was 33 in the control group. On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P < 0.05). On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group, whereas radiographic total score was 15 and histologic total score was 40 in the control group. On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group, it was not statistically significant (P > 0.05).

CONCLUSIONIloprost delays fracture healing in early stage in rats.

Animals ; Epoprostenol ; pharmacology ; Fracture Healing ; drug effects ; Fractures, Bone ; pathology ; Iloprost ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Tibial Fractures ; pathology ; Wound Healing ; drug effects

OBJECTIVETo assess the effect of intermittent subcutaneous injections of signal-selective parathyroid hormone (PTH) peptide analog on fracture healing in orchiectomized mouse models.

METHODSThirty-six 7-week-old C57/BL male mice were orchiectomized and injected with hPTH(1-34), the signal-selective PTH peptide analog [Gly(1), Arg(19)]hPTH (1-34), or an identical volume of vehicle 1 week after induction of femoral fracture. At 14 and 28 days after the operation, the mice were sacrificed for measurement of bone mineral density (BMD) and bone mineral content (BMC) of the callus using by dual energy X-ray absorptiometry. The bone healing was evaluated by radiography, biomechanical testing, micro-computed tomography (Micro-CT) and histological examination.

RESULTSAt 14 days after the operation, BMD in PTH peptide analog group was significantly increased (P<0.05). The mouse models treated with the PTH peptide analog showed significantly lower ultimate bending force and bending rigidity than those with hPTH(1-34) treatment. X-ray and Micro-CT scanning showed that callus transformation and remodeling was better in PTH peptide analog group than in the vehicle control group but poorer than in hPTH(1-34) group.

CONCLUSIONThe signaling-selective PTH peptide analog G1, R19 (1-28) can accelerate fracture healing in orchiectomized mouse models, in which process cAMP/PKA pathway plays an important role.

Animals ; Bone Density ; Fracture Healing ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Orchiectomy ; Parathyroid Hormone ; analogs & derivatives ; pharmacology ; Signal Transduction

OBJECTIVETo study the effects of administration or local application of epimedium on the fracture healing in osteoporosis rats.

METHODSEighty-two 4-month old clean female rats, 210-250 g, were randomly divided into the experimental group (n = 75) and the control group (n = 7). The bilateral ovaries were resected in the experimental group, while only little fat tissue around the ovary was resected in the control group. Ten weeks after operation the osteoporosis model was successfully established verified by bone densitometry and scanning electron microscopy (SEM). The femur fracture models were established in the rest 72 rats of the experimental group. They were randomly divided into 3 groups, 24 in each group, i.e., the calcium phosphate cement (CPC) group (Group A), the CPC-epimedium group (Group B), and the epimedium administration group (Group C). The serum alkaline phosphatase (ALP) levels of the 3 groups were determined 2, 4, 8, and 12 weeks after surgery. The vitodynamical test and observation of the histological section were performed.

RESULTSThe serum ALP levels increased to some extent in the 3 groups 2, 4, and 8 weeks after bone fracture surgery. But the increase was more obvious in Group B with statistical difference shown when compared with Group A and C (P < 0.05). The ALP level in Group B decreased to the normal range till the 12th week. The bone fracture had not completely healed in Group C and A. Their ALP levels decreased to some extent, but were still maintained to a comparatively higher level, showing statistical difference when compared with that of Group B (P < 0.05). These results were agreeable with the results of the histological observation. Better bone activity promoting results were shown in Group B. The vitodynamical test results of the femur of Group B were all higher than those of Group A and C at each time point (P < 0.05).

CONCLUSIONSLocal application of epimedium could accelerate the fracture healing in osteoporosis rats. It showed better effects when compared with oral administration at the same dose.

Alkaline Phosphatase ; blood ; Animals ; Bone Cements ; therapeutic use ; Calcium Phosphates ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Epimedium ; Female ; Fracture Healing ; drug effects ; Fractures, Bone ; drug therapy ; etiology ; Osteoporosis ; complications ; drug therapy ; Ovariectomy ; Rats

Occurance of atrophic nonunion is a complex process. Previous studies suggested that atrophic nonunion was mainly due to lack of blood supply of fracture fragments, but recent studies found that blood supply was not deficiency in middle and late stages, indicating that decreased osteogenic factors and blood supply in early stages might play an important role in morbidity. Current effective treatment measures for atrophic nonunion mainly include bone graft and fixation,physical therapy, local injection therapy. All-round preventive could reduce incidence of atrophic nonunion. Atrophic nonunion is still a troublesome complication of fractures in orthopaedics, and more attention should be paid for its effective prevention and treatment. The paper summarized recent original articles about atrophic nonunion and reviewed the occurrence mechanisms, diagnosis, prevention and treatment measures of this disease.
Atrophy ; diagnosis ; etiology ; prevention & control ; therapy ; Fracture Healing ; drug effects ; Fractures, Bone ; pathology ; Humans

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing.
Bone Density/drug effects ; Diaphyses/drug effects/injuries ; Diphosphonates/*adverse effects ; Female ; Femoral Fractures/*chemically induced/diagnosis/surgery ; Fracture Fixation, Internal ; Fracture Healing/drug effects ; Fractures, Spontaneous/*chemically induced/diagnosis/surgery ; Fractures, Stress/*chemically induced/diagnosis/surgery ; Humans ; Middle Aged ; Osteoporosis/*drug therapy ; Radiopharmaceuticals/diagnostic use ; Technetium Tc 99m Medronate/analogs & derivatives/diagnostic use ; Treatment Outcome ; Whole Body Imaging

This study was designed to investigate the effects of some Traditional Chinese Medicine (TCM) agents on bone resorption and morphometric features of osteoclasts as well as their relationships. TCM ShengGuZaiZaoSan and XianLingGuBao, were used to treat the experimental fracture. Thirty 6-month-old Chinchilla rabbits were used for the establishment of animal models each with a 3 mm bone defect in the middle of left radius as well as of right radius. These models were divided randomly into 3 groups : ShengGuZaiZaoSan Group (Group A), XianLingGuBao groups (Group B) and control-group (Group C). Every group was further divided into 2 subgroups: a former sacrificed group (14 days after operation) and a latter sacrificed group (31 days after operation). After the rabbits being killed, the samples of their undecalcified calli were subjected to the morphometry study of bone resorption and osteoclasts. Group A had more bone resorption, compared with Group B and C. Both Groups A and B exhibited some changed morphometric features of osteoclasts as compared with Group C (P < 0.05). Simple correlation analysis indicated that bone resorption is mainly correlated with osteoclast numbers, and that in individual group, bone resorption is correlated with osteoclast form factor, area and mean photodensity (P < 0.05). These allow us to conclude that ShengGuZaiZaoSan can increase bone resorption and accelerate bone remodeling by increasing osteoclast numbers at the former stage and can enhance osteoclast function at the latter stage. These changes are beneficial to fracture healing.
Animals ; Bone Remodeling ; drug effects ; Bone Resorption ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fracture Healing ; drug effects ; physiology ; Male ; Osteoclasts ; drug effects ; pathology ; Phytotherapy ; Rabbits ; Radius Fractures ; drug therapy ; pathology ; physiopathology ; Random Allocation

PURPOSE: Bisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model. MATERIALS AND METHODS: We performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography. RESULTS: The mean ICP was 61.8+/-15.7ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p=0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p= 0.183). High ICP decreased the bone mineral density of the femoral head (p=0.005). CONCLUSION: High concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone.
Animals ; Bone Density Conservation Agents/*pharmacology ; Diphosphonates/*pharmacology ; Disease Models, Animal ; Female ; Femur/*drug effects/physiology ; Fracture Healing/physiology ; Osteoporosis/*metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Mechanical

OBJECTIVETo study the clinical effect of Jieguxujin granule (JGXJG) on fracture and its effect on serum content of calcitonin gene related peptide (CGRP).

METHODSFour hundred patients with fracture were randomly divided into 2 groups, the JGXJG treated group and the control group treated with Sanqi tablet (SQT). Serum CGRP was tested with radioimmunoassay once every 3 days for 5 times, and X-ray examination was taken once each week for 10 weeks.

RESULTSThe healing time of fracture and osteotylus forming time in the JGXJG group was shorter than those in the SQT group significantly (P < 0.005). Serum CGRP content in JGXJG group was higher remarkably (P < 0.05, P < 0.01).

CONCLUSIONJGXJG showed evident effect in promoting union of fracture healing, it could also increase the CGRP content in serum.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calcitonin Gene-Related Peptide ; blood ; Child ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Femoral Fractures ; drug therapy ; Fracture Healing ; drug effects ; Fractures, Bone ; drug therapy ; Humans ; Humeral Fractures ; drug therapy ; Male ; Middle Aged ; Phytotherapy ; Tibial Fractures ; drug therapy

To investigate the influence of high molecular weight polyethylene (HMWP) on the viability of osteoblasts and new bone formation in the process of fracture healing, the osteoblasts derived from adult human bone marrow were cultured in HMWP maceration extract and normal culture medium. The viability of the osteoblasts was measured by MTT assay, and the function of the osteoblasts was detected by use of alkaline phosphatase test kit. The locked double-plating (steel plate and HMWP plate) was implanted and fixed at the artificial fracture of distal femur of dogs. Specimens were gained at 3, 6, 9 and 12 weeks postoperatively, examined with macroscopy, microscope and scanning electron microscope (SEM). The results showed that HMWP did no harm to osteoblasts. There is no significant difference in activities of proliferation and alkaline phosphatase between HMWP maceration extract and normal culture medium at each observation time of at 2,4,8, and 14 dyas (P>0. 05). Bone tissue under the implanted HMWP plate manifested no absorption; the new bones formed under the HMWP plate and gradually matured as time went on. It is demonstrated in this study that HMWP has no adverse influence on the viability of osteoblasts and new bone formation and it can be used as internal fixation implant in treating fractures.
Animals ; Biocompatible Materials ; chemistry ; pharmacology ; Cells, Cultured ; Dogs ; Female ; Femoral Fractures ; surgery ; Fracture Fixation, Internal ; Fracture Healing ; physiology ; Humans ; Implants, Experimental ; Internal Fixators ; Male ; Osteoblasts ; cytology ; drug effects ; Osteogenesis ; drug effects ; Polyethylene ; chemistry ; pharmacology