Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis.

Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage. MG132 treatment greatly reduced radiation-induced apoptosis in cultured osteoblastic cells. This survival effect was owing to accelerated DNA repair as revealed by γH2AX foci and comet assays and to the up-regulation of Ku70 and DNA-dependent protein kinase, catalytic subunit, essential DNA repair proteins in the nonhomologous end-joining pathway. Administration of bortezomib (Bzb) reversed the loss of trabecular bone structure and strength in mice at 4 wk after focal radiation. Histomorphometry revealed that Bzb significantly increased the number of osteoblasts and activity in the irradiated area and suppressed the number and activity of osteoclasts, regardless of irradiation. Two weeks of Bzb treatment accelerated DNA repair in bone-lining osteoblasts and thus promoted their survival. Meanwhile, it also inhibited bone marrow adiposity. Taken together, we demonstrate a novel role of proteasome inhibitors in treating radiation-induced osteoporosis.-Chandra, A., Wang, L., Young, T., Zhong, L., Tseng, W.-J., Levine, M. A., Cengel, K., Liu, X. S., Zhang, Y., Pignolo, R. J., Qin, L. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis.

Therapeutic ionizing radiation induced bone loss: a review of in vivo and in vitro findings.

Radiation therapy is one of the routine treatment modalities for cancer patients. Ionizing radiation (IR) can induce bone loss, and consequently increases the risk of fractures with delayed and nonunion of the bone in the cancer patients who receive radiotherapy. The orchestrated bone remodeling can be disrupted due to the affected behaviors of bone cells, including bone mesenchymal stem cells (BMSCs), osteoblasts and osteoclasts. BMSCs and osteoblasts are relatively radioresistant compared with osteoclasts and its progenitors. Owing to different radiosensitivities of bone cells, unbalanced bone remodeling caused by IR is closely associated with the dose absorbed. For doses less than 2 Gy, osteoclastogenesis and adipogenesis by BMSCs are enhanced, while there are limited effects on osteoblasts. High doses (>10 Gy) induce disrupted architecture of bone, which is usually related to decreased osteogenic potential. In this review, studies elucidating the biological effects of IR on bone cells (BMSCs, osteoblasts and osteoclasts) are summarized. Several potential preventions and therapies are also proposed.

Alveolar bone remodeling after tooth extraction in irradiated mandible: An experimental study with canine model.

OBJECTIVES: The aim of the present study is to investigate the morphological and cellular changes in dental extraction socket that has been irradiated after the tooth extraction and to describe morphological characteristics of the osteocytes and osteocyte-lacunar-canalicular network (LCN) by scanning electron microscopy (SEM). MATERIAL AND METHODS: Five beagle dogs aged 1-2 years were used in this study. One side of each mandible was irradiated in two sessions and the other side of mandible (non-irradiated) served as a control. The mandible bone blocks were processed by bulk staining en bloc in basic fuchsin and the specimens were embedded routinely in polymethyl methacrylate resin without preliminary decalcification. All blocks were subjected to micro-CT imaging, after that the specimens were prepared for light microscopy and SEM. RESULTS: Alterations in bone macrostructure are minimal in irradiated bone, but the changes in LCN are clear. In the area of the tooth extraction socket, the connections of osteocytes to the vessels and to neighboring osteocytes were not observed both in irradiated and nonirradiated bone. However, osteoclasts were located in the bone surface entering inside to the bone between osteons. In the lamellar bone of lateral sides, a decrease in canalicular connections between osteocytes and periosteum was found in irradiated bone as compared to the non-irradiated side. CONCLUSIONS: The novelty of the present study is that radiation disrupts osteocytes and their dendrites.

Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.

We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees.

Effects of pulsed electromagnetic fields on postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is considered to be a well-defined subject that has caused high morbidity and mortality. In elderly women diagnosed with PMOP, low bone mass and fragile bone strength have been proven to significantly increase risk of fragility fractures. Currently, various anabolic and anti-resorptive therapies have been employed in an attempt to retain healthy bone mass and strength. Pulsed electromagnetic fields (PEMFs), first applied in treating patients with delayed fracture healing and nonunions, may turn out to be another potential and effective therapy for PMOP. PEMFs can enhance osteoblastogenesis and inhibit osteoclastogenesis, thus contributing to an increase in bone mass and strength. However, accurate mechanisms of the positive effects of PEMFs on PMOP remain to be further elucidated. This review attempts to summarize recent advances of PEMFs in treating PMOP based on clinical trials, and animal and cellular studies. Possible mechanisms are also introduced, and the future possibility of application of PEMFs on PMOP are further explored and discussed. Bioelectromagnetics. 38:406-424, 2017. © 2017 Wiley Periodicals, Inc.

Effect of Low-intensity Pulsed Ultrasound on the Mandibular Remodeling Following Inferior Alveolar Nerve Transection.

Objective To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the mandibular remodeling following inferior alveolar nerve transection (IANX) and to optimize the parameters of LIPUS in the treatment of nerve injury. Methods IANX was performed in male Sprague-Dawley rats. Four weeks after IANX,the effect of daily LIPUS (from day 1) on the transected inferior alveolar nerve was examined in terms of sensitivity to mechanical stimulation. Moreover,histopathologic changes of mandibles were analyzed by micro-CT,HE staining,Masson trichrome staining,and immunohistochemical staining. Results LIPUS promoted the recovery of inferior alveolar nerve injury after transection. HE staining displayed the improvement of trabecular thickness and continuity. LIPUS with higher duty ratios had more obvious effect on bone remodeling. Conclusion LIPUS promotes the mandibular remodeling following IANX.

Low-level laser therapy and invisible removal aligners.

It seems that Low Level Laser Therapy (LLLT) stimulates orthodontic tooth movements, increasing the alveolar bone turnover. The aim of this study is to evaluate how LLLT can influence the orthodontic treatment with invisible removal aligner. A sample of 21 subjects was divided into two groups, a laser group (10 patients) and a control group (11 patients). All subjects were instructed to wear each aligner 12 hours a day for 2 weeks. Laser external bio-stimulation was given in the laser group every second week. The laser group successfully finished the treatment, while at 3rd – 5th aligner the control group did not finish the treatment. Laser treatment seemed to be better than treatment without laser. LLLT combined with aligners is able to favour, in 12 hours, the same tooth movement obtained by wearing the aligner 22 hours a day, according to the traditional protocol. This aspect could be useful for those patients who prefer not to use the aligners during the day. LLLT makes invisible removal aligner treatment more comfortable also because during the day the patients have to wear the aligners less hours than the treatment without laser.

Effect of low-level laser therapy on orthodontic tooth movement into bone-grafted alveolar defects.

INTRODUCTION: The objective of this study was to investigate the effect of low-level laser therapy (LLLT) on the rate of orthodontic tooth movement (OTM) into bone-grafted alveolar defects based on different healing states. METHODS: Ten male beagles were randomly allocated to 3 groups: group C, OTM alone as a control; group G, OTM into the grafted defects; group GL, OTM into the grafted defects with LLLT. The maxillary second premolars were protracted into the defects for 6 weeks, immediately (G-0 and GL-0) and at 2 weeks (G-2 and GL-2) after surgery. The defects were irradiated with a diode laser (dose, 4.5 J/cm(2)) every other day for 2 weeks. The rates of OTM and alveolar bone apposition, and maturational states of the defects were analyzed by histomorphometry, microcomputed tomography, and histology. RESULTS: The total amounts of OTM and new bone apposition rates were decreased by LLLT, with increased bone mineral density and trabecular maturation in the defects. Group GL-2 had the slowest movement with root resorption in relation to less woven bone in the hypermatured defect. CONCLUSIONS: LLLT significantly decreased the rate of OTM into the bone-grafted surgical defects by accelerating defect healing and maturation, particularly when the start of postoperative OTM was delayed.

A 635-nm light-emitting diode (LED) therapy inhibits bone resorptive osteoclast formation by regulating the actin cytoskeleton.

Bone diseases such as osteoporosis are mainly caused by upregulated activity of osteoclasts. The present study was designed to examine the effects of light-emitting diode (LED) irradiation on the formation and activity of multinucleated osteoclasts, specifically "round-shaped" osteoclast cells (ROC) in different cell types derived from mouse. After 635-nm LED irradiation, the cell viability was evaluated by MTT assay. The amount of total tartrate-resistant acid phosphatase (TRAP) + osteoclast and the number of ROC cells were also estimated by TRAP solution assay and TRAP staining, respectively. Actin rings were stained with rhodamine-conjugated phalloidin, and resorption assay was performed by dentin slices. In addition, gene expression levels between the control and irradiation groups were evaluated by RT-PCR. In a morphological analysis, the formation of ROC was significantly inhibited by 635-nm LED irradiation in the different cell types. Actin rings were seen at cell peripheries in most ROC cells of the control group, but patches containing disorganized actin were found in the irradiation group. Both the number of ROCs and bone resorption activity were much lower in the irradiation group than in the control group. Also, the gene expression levels involved in actin ring formation such as integrin ß3 and c-Src decreased in RT-PCR analysis. Overall, 635-nm LED therapy may play a pivotal role in regulating bone remodeling, and it may prove to be a valuable tool to prevent bone loss in osteoporosis and other resorptive bone diseases.

Experimental remodellation of extracorporeal irradiated autogenous and allogenic patellar grafts.

BACKGROUND: Irradiated autografts have been used to aid the recovery of bone defects, and the results are well documented. Recently, bone allografts with tendinous attachments have been used to restore the function of joints. Similar reconstructions can be performed with irradiated autografts. However, little information is available on the biology of extracorporeal irradiated tendon autografts. QUESTIONS/PURPOSES: An experimental rabbit model was used to investigate the quality of healing and remodeling of the irradiated autogenous patellar tendon graft after 3 and 12 weeks using immunohistochemical and morphometric analyses. METHODS: New Zealand rabbits (n = 40) were randomly divided into autograft and allograft groups. The right knees of all animals served as the control (sham). The patellar tendon graft of the control right knee was reimplanted into its original location without any processing, while the patellar tendon of the left knee in the autograft group was reimplanted into the original location after 50 Gy irradiation. In the allograft group, the patellar tendon was sutured to the knee of another rabbit following 50 Gy irradiation. Five rabbits from each group were sacrificed and examined histologically. RESULTS: There were significant differences in the number of fibroblasts after 12 weeks between allograft and sham groups (P = 0.002). On the other hand, there were no differences between the allograft and autograft groups at the 12th week (P = 0.139). The difference in fibroblast numbers between autograft and allograft groups was statistically significant after the 3rd week (P < 0.05). Collagen fibril thickness was different between both the allograft and sham groups (P = 0.002) and the allograft and autograft groups at the 12th week (P = 0.000). Collagen fibrils were thicker in the sham and autograft groups compared with the allograft group at the 3rd week of evaluation (P < 0.05). The Ki67 index was significantly different between the allograft and sham groups at the 12th week (P < 0.032), while there was no difference between the allograft and autograft groups (P > 0.05). At the 3rd week, Ki67 reactivity was higher in the allograft group compared with the other two groups (P < 0.05).

The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice.

Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 µCi (45)Ca. Thirty days post-(45)Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of (45)Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal (45)Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via (45)Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar (45)Ca excretion but different bone microarchitectural responses. The (45)Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

Metrical and histological investigation of the effects of low-level laser therapy on orthodontic tooth movement.

The aim of this study was to evaluate the effects of 820-nm diode laser on osteoclastic and osteoblastic cell proliferation-activity and RANKL/OPG release during orthodontic tooth movement. Thirty-eight albino Wistar rats were used for this experiment. Maxillary incisors of the subjects were moved orthodontically by a helical spring with force of 20 g. An 820-nm Ga-Al-As diode laser with an output power of 100 mW and a fiber probe with spot size of 2 mm in diameter were used for laser treatment and irradiations were performed on 5 points at the distal side of the tooth root on the first, second, and 3rd days of the experiment. Total laser energy of 54 J (100 mW, 3.18 W/cm(2), 1717.2 J/cm(2)) was applied to group II and a total of 15 J (100 mW, 3.18 W/cm(2), 477 J/cm(2)) to group III. The experiment lasted for 8 days. The number of osteoclasts, osteoblasts, inflammatory cells and capillaries, and new bone formation were evaluated histologically. Besides immunohistochemical staining of PCNA, RANKL and OPG were also performed. No statistical difference was found for the amount of tooth movement in between the control and study groups (p > 0.05). The number of osteoclasts, osteoblasts, inflammatory cells, capillary vascularization, and new bone formation were found to be increased significantly in group II (p < 0.05). Immunohistochemical staining findings showed that RANKL immunoreactivity was stronger in group II than in the other groups. As to OPG immunoreactivity, no difference was found between the groups. Immunohistochemical parameters were higher in group III than in group I, while both were lower than group II. On the basis of these findings, low-level laser irradiation accelerates the bone remodeling process by stimulating osteoblastic and osteoclastic cell proliferation and function during orthodontic tooth movement.

Influence of carbon dioxide laser irradiation on the healing process of extraction sockets.

OBJECTIVE: To clarify the healing-promoting effects of carbon dioxide laser irradiation in high and low reactive-level laser therapies (HLLT and LLLT, respectively) on extraction sockets after tooth extraction. MATERIAL AND METHODS: Forty-two 5-week-old male Wistar rats were divided into laser irradiation and non-irradiation (control) groups and compared. The laser-irradiation group underwent HLLT immediately after tooth extraction and then LLLT 1 day post-extraction. Tissue was excised 6 h and 3, 7, or 21 days after extraction and histopathologically investigated. The alveolar crest height was measured osteomorphometrically 21 days post-extraction, and granulation tissue in the extraction socket surface layer was immunohistologically investigated using anti-α-smooth muscle actin (anti-α-SMA) antibody 3 and 7 days post-extraction. RESULTS: Many osteoclasts appeared and active bone resorption was noted in the irradiation group 3 days after extraction compared to the controls. On Day 7, new bone formation started around the extraction socket in the control group, but from the superficial to over the middle layer of the socket in the irradiation group. On Day 21, a concavity existed in the alveolar crest region in the controls, whereas this region was flat, with no concavity, in the irradiation group. On osteomorphometry, the alveolar crest height was significantly higher in the irradiation (0.7791 ± 0.0122) than the control (0.6516 ± 0.0181) group (P < 0.05). On immunostaining, many α-SMA-positive cells were noted in the control group, but very few in the irradiation group. CONCLUSION: Laser-irradiated extraction wound healing showed characteristics different from those of the normal healing process, suggesting a favorable healing-promoting effect.

Bone regeneration after radiotherapy in an animal model.

PURPOSE: The study aimed to evaluate dosage-dependent effects of irradiation on bone regeneration and established a radiation-compromised rabbit model of mandibular distraction osteogenesis. MATERIALS AND METHODS: Twenty-three rabbits were divided randomly into 7 groups. Group A served as the control group, whereas experimental groups B, C, D, E, F, and G received preoperative irradiation at doses of 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0 Gy, respectively, for 5 fractions. After 1 month, all rabbits underwent osteotomy and distraction osteogenesis with 7 days of latency, 11 days of active distraction at a rate of 0.9 mm/d, and 4 weeks of consolidation; rabbit mandibles were subsequently subjected to histologic, radiographic, and micro-computed tomography analysis. RESULTS: With increasing doses of irradiation, bone regeneration was markedly hampered. Radiographically, the high-dose groups (8.5 and 9.0 Gy) presented obscure cortical lines. Histologically, in the 8.5- and 9.0-Gy groups, cortical bones were not completely formed, and in the medullary cavity, there existed a large amount of fibrous tissue. CONCLUSION: Radiotherapy compromises bone regeneration during distraction osteogenesis, and the adverse effect is dose dependent.

Low-energy laser irradiation facilitates the velocity of tooth movement and the expressions of matrix metalloproteinase-9, cathepsin K, and alpha(v) beta(3) integrin in rats.

It has previously been reported that low-energy laser irradiation stimulated the velocity of tooth movement via the receptor activator of nuclear factor kappa B (RANK)/RANK ligand and the macrophage colony-stimulating factor/its receptor (c-Fms) systems. Matrix metalloproteinase (MMP)-9, cathepsin K, and alpha(v) beta(3) [alpha(v)beta3] integrin are essential for osteoclastogenesis; therefore, the present study was designed to examine the effects of low-energy laser irradiation on the expression of MMP-9, cathepsin K, and alpha(v)beta3 integrin during experimental tooth movement. Fifty male, 6-week-old Wistar strain rats were used in the experiment. A total force of 10g was applied to the rat molars to induce tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moving tooth and, after 7 days, the amount of tooth movement was measured. To determine the amount of tooth movement, plaster models of the maxillae were made using a silicone impression material before (day 0) and after tooth movement (days 1, 2, 3, 4, and 7). The models were scanned using a contact-type three-dimensional (3-D) measurement apparatus. Immunohistochemical staining for MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 was performed. Intergroup comparisons of the average values were conducted with a Mann-Whitney U-test for tooth movement and the number of tartrate-resistant acid phosphatase (TRAP), MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3-positive cells. In the laser-irradiated group, the amount of tooth movement was significantly greater than that in the non-irradiated group at the end of the experiment (P < 0.05). Cells positively stained with TRAP, MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 were found to be significantly increased in the irradiated group on days 2-7 compared with those in the non-irradiated group (P < 0.05). These findings suggest that low-energy laser irradiation facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 expression in rats.

Bone mass and microarchitecture of irradiated and bone marrow-transplanted mice: influences of the donor strain.

UNLABELLED: Total body irradiation and bone marrow transplantation induced dramatic trabecular bone loss and cortical thickening in mice. Transplanted cells were engrafted in bone marrow, along trabeculae, and in periosteal and endosteal envelopes. None of the osteocytes were of donor origin. Bone microarchitecture of transplanted mice changed to tend toward the donor phenotype. INTRODUCTION: Osteopenia and osteoporosis are complications of bone marrow transplants (BMT) attributed to related chemotherapy. However, the specific influence of total body irradiation (TBI) is unknown. METHODS: We investigated the effects of TBI and BMT on bone mass and microarchitecture by micro-CT. Eighteen C57Bl/6 (B6) mice receiving lethal TBI had a BMT with marrow cells from green fluorescent protein--transgenic-C57Bl/6 (GFP) mice. Transplanted (T(GFP)B6), B6, and GFP mice were euthanized 1, 3, and 6 months after BMT or at a related age. RESULTS: T(GFP)B6 presented a dramatic bone loss compared with B6 and did not restore their trabecular bone mass over time, despite a cortical thickening 6 months after BMT. Serum testosterone levels were not significantly reduced after BMT. During aging, GFP mice have less trabeculae, thicker cortices, but a narrower femoral shaft than B6 mice. From 3 months after BMT, cortical characteristics of T(GFP)B6 mice differed statistically from B6 mice and were identical to those of GFP mice. GFP(+) cells were located along trabecular surfaces and in periosteal and endosteal envelopes, but none of the osteocytes expressed GFP. CONCLUSION: Our findings suggest that engrafted cells did not restore the irradiation-induced trabecular bone loss, but reconstituted a marrow microenvironment and bone remodeling similar to those of the donor. The effects of irradiation and graft on bone remodeling differed between cortical and trabecular bone.

Radiation dose to trabecular bone marrow stem cells from (3)H, (14)C and selected alpha-emitters incorporated in a bone remodeling compartment.

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for (3)H, (14)C and a set of alpha-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 microm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 microm endosteum for (3)H, (14)C and alpha-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal alpha-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

Bone and bone turnover.

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

Low-energy laser irradiation accelerates the velocity of tooth movement via stimulation of the alveolar bone remodeling.

INTRODUCTION: Previously, the authors have reported the acceleration of tooth movement and osteoclastogenesis on the pressure site in an experimental tooth movement model by low-energy laser irradiation (LELI), which stimulated the RANK/RANKL system and c-fms/macrophage colony-stimulating factor system. However, the effect of LELI on osteogenesis on the tension site is not known clearly. Moreover, the temporal changes in alveolar bone during tooth movement have not been investigated as yet. Therefore, the present study was designed to examine the effects of LELI on alveolar bone remodeling during experimental tooth movement, and observe the temporal bone mineral density (BMD) using micro-computed tomography (muCT). MATERIALS AND METHODS: To induce experimental tooth movement in rats, 10 g force was applied to the upper right first molar with Nickel titanium closed-coil. Next, a gallium-aluminum-arsenide (Ga-Al-As) diode laser was used to irradiate the area around the moved tooth, and BMD and the amount of tooth movement were measured by muCT scanning for 21 days. Histopathological examination was also performed. RESULTS: The amount of tooth movement in the LELI group was significantly greater than in the non-irradiation group by the end of the experimental period. Further, compared with the non-irradiation group, the fall of BMD was less in the LELI group. CONCLUSION: These findings suggest that LELI accelerates the velocity of tooth movement via stimulation of the alveolar bone remodeling.

[Effect of ultraviolet irradiation through glass on the level of 25-hydroxy vitamin D and bone metabolism in rats].

OBJECTIVE: Some research has shown that there is a dose-dependent relationship between ultraviolet B (UVB) and serum levels of 25-hydroxy vitamin D[25-(OH)D]\. Vitamin D is correlated with bone metabolism. This study aimed to explore the effect of UVB irradiation through glass on serum levels of 25-(OH)D and bone metabolism in rats. METHODS: Wistar rats were fed with vitamin D deficient diet and randomly divided into three groups: no UVB exposure, direct UVB exposure (160 min/d) and indirect UVB exposure (through glass) (160 min/d). By 21 days after exposure, bone mineral density (BMD) and serum levels of 25-(OH)D, parathyroid hormone (PTH), osteocalcin (OC), bone alkaline phosphatase (BALP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) were measured. RESULTS: BMD (0.036+/-0.002 g/cm2) in the indirect UVB exposure group was significantly higher than that in the no UVB exposure group (0.029+/-0.002 g/cm2) (<0.01). Serum ICTP level in the indirect UVB exposure group was significantly lower than that in the no UVB exposure group (0.181+/-0.067 microg/L vs 0.194+/-0.066 microg/L; <0.01). Serum levels of PTH, 25-(OH)D, BALP and OC in the indirect UVB exposure group were not significantly different from those in the no UVB exposure group. Compared with the direct UVB exposure group, serum levels of OC (0.559+/-0.067 ng/mL vs 0.278+/-0.067 ng/mL; <0.05) and PTH (0.181+/-0.067 microg/L vs 0.109+/-0.067 microg/L; <0.05) in the indirect UVB exposure group significantly increased, while serum levels of 25-(OH)D significantly decreased (28.67+/-1.35 nmol/L vs 34.69+/-4.30 nmol/L; <0.01). There were no significant differences in BMD and serum levels of BALP and ICTP between the indirect UVB exposure and the direct UVB exposure groups. CONCLUSIONS: UVB irradiation through glass cannot elevate serum levels of 25-(OH)D, but can decrease bone turnover rate and increase BMD. The effect of UVB irradiation through glass on bone metabolism is similar to that of direct UVB irradiation.