Bone health and osteoporosis screening in gynecologic cancer survivors.

Cancer treatment-induced bone loss is a known side effect of cancer therapy that increases the risk of osteoporosis and bone fracture. Women with gynecologic cancer are at increased risk of bone loss secondary to the combined effect of oophorectomy and adjuvant therapies. Data regarding bone loss in women with gynecologic cancers are overall lacking compared to other cancer populations. Consequently, guidelines for osteoporosis screening in women with cancer are largely based on data generated among non-gynecologic cancer survivors. This article reviews current available data of bone health in women with gynecologic cancer, summarizes best-available guidelines for screening for osteoporosis in women with cancer, and provides guidance for osteoporosis screening in women with gynecologic cancers based on best available evidence.

Therapeutic effect of pulsed electromagnetic field on bone wound healing in rats.

This study aimed to investigate the therapeutic effect of pulsed electromagnetic field (PEMF) on bone wound in rats as a potential therapy for bone fracture-related conditions. Male rats, aged 3 months, were used to construct model of bone wounding. Wound models were randomly selected to receive PEMF therapy at 1 to 10 mT intensity. Models that did not receive PEMF therapy were used as control. The serum concentrations of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were determined. Bone density and biomechanical properties of callus were measured using a tensile tester. Compared with control, rats subjected to PEMF therapy had similar weight gain, but significantly higher levels of serum Ca and ALP (P < .05) at 5 and 10 mT, while the serum level of P remained unchanged after PEMF therapy. The bone mineral density of callus increased after the therapy, particularly, after 5 and 10 mT therapy (P < .05). Biomechanical measurements showed that 21 days after the therapy, the maximum load, fracture load, elastic load and bending energy were significantly greater in rats receiving 5 and 10 mT PEMF therapy as compared with control (P < .05). Our experiments demonstrate that PEMF at 5 and 10 mT can significantly accelerate wound healing and enhance the repairing ability of bone tissue.

Determinants of bone health in adults Polish women: The influence of physical activity, nutrition, sun exposure and biological factors.

PURPOSE: The aim of this study was to assess the determinants of bone health in the group of women over 40 years old. Lifestyle factors such as past and present physical activity, past and present sun exposure, current dietary intake of calcium and vitamin D, nutritional status as measured by BMI, family history of osteoporosis and current hormonal status were analysed. METHODS: The study involved 500 women over 40 years old. All examined women was the same ethnicity- European origin. Methods used: densitometry method (DXA), bioelectrical impedance analysis, International Physical Activity Questionnaire, nutrition questionnaire, past and present sun exposure questionnaire. Past and present physical activity, past and present sun exposure and sufficient level of calcium in the diet proved to be the most important factors determining mineralization of bone tissue of women. In order to indicate an independent association of the correct bone tissue mineralization with individual factors, multivariate analysis was used-logistic regression. RESULTS: The norm BMD in the distal part of the forearm was strongly influenced: recommended dietary calcium intake (OR = 5.95; p = 0.003), moderately (OR = 1.88; p = 0.053) and high (OR = 14.0; p<0.001) past physical activity, sufficient (OR = 4.97; p<0.001) and high (OR = 18.9; p = 0.004) level of present physical activity, sufficient past (OR = 5.15; p<0.001) and sufficient present sun exposure (OR = 10.0; p<0.001). The chance for the BMD prox norm was also increased several times: high past physical activity (OR = 68.4; p<0.0001) and sufficient past sun exposure (OR = 10.6; p<0.001), moderate past activity (OR = 4.20; p<0.001), sufficient (OR = 6.13; p<0.001) and high (OR = 10.0; p<0.001) present physical activity, sufficient present sun exposure (OR = 9.09; p<0.0001), recommended intake of calcium (OR = 9.57; p<0.001) and vitamin D (OR = 2.68; p = 0.052). Whereas e significantly lower likelihood for the BMD prox norm was found in women with the oldest hormonal status (postmenopausal period) (OR = 0.18; p<0.001), with osteoporosis in the family (OR = 0.37; p<0.001) and living in an agglomeration (OR = 0.68; p = 0.03). CONCLUSION: Interventions to increase physical activity, especially outdoors, may help reduce risk of osteoporosis, fractures and subsequent healthcare costs.

Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice.

Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight. Furthermore, we show that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity. Based on our findings, a dietary supplementation with DP could be an effective countermeasure against the skeletal deficits observed in astronauts during spaceflight.

Effect of Sunlight Exposure on Vitamin D Status of Individuals Living in a Nursing Home and Their Own Homes.

INTRODUCTION/BACKGROUND: The present study was carried out to determine prevalence of vitamin D deficiency and related factors in individuals living in nursing home and their own homes. METHODOLOGY: This cross-sectional study included 72 elderly people 60 yr and older. All subjects were given a questionnaire form evaluating their individual characteristics, eating habits which affected their vitamin D status, wearing habits, and their duration of sun exposure and a Standardized Mini Mental Test evaluating their cognitive levels. Serum 25(OH)D, calcium, parathyroid hormone, alkaline phosphatase and phosphorus levels, and bone mineral density measurements were also considered. RESULTS: Vitamin D deficiency was observed in 47% of elderly people (nursing home: 64%, own home 31%, p = 0.05). Both 25(OH)D (14 ± 8 vs 27 ± 10, respectively, p < 0.001) and ultraviolet index value (0.63 ± 0.3 vs 0.92 ± 0.27, respectively, p < 0.001) were lower in people living in nursing home compared to ones living in their own homes. Parathyroid hormone level, on the other hand, was lower in people living in own homes. Vitamin D deficiency/insufficiency was more common in elderly people living in nursing home (100%) compared to those living in their own homes (64%) (p = 0.003). Osteopenia and osteoporosis incidence rates were also higher in elderly people living in nursing home (p = 0.001). No significant associations were found between vitamin D status and body mass index, smoking or dietary habits (p > 0.05). As levels of benefiting from ultraviolet index increased, significantly improvements were observed in 25(OH)D levels (p < 0.001). CONCLUSIONS: In elderly people living in nursing home, vitamin D deficiency was higher and benefitting from ultraviolet index was lower compared to elderly people living in their own homes. Vitamin D deficiency could be prevented in elderly people, especially ones living in nursing homes, through enough sun exposure with appropriate clothing.

Influence of radiation exposure pattern on the bone injury and osteoclastogenesis in a rat model.

Radiotherapy, one of the clinical treatments of cancer, is accompanied by a high risk of damage to healthy tissues, such as bone loss and increased risk of fractures. The aim of the present study was to establish a rat model of local and systemic bone injury by focal irradiation, in order to study the etiological mechanism and intervention. The proximal metaphyseal region of the left hindlimb of male Sprague­Dawley rats were exposed to a single 2 Gy or three 8 Gy doses delivered on days 1, 3 and 5 using a small animal irradiator, the changes in bone volume and microarchitecture were evaluated, and the mineral apposition rate (MAR) was assessed. Furthermore, bone marrow­derived macrophages (BMMs) were isolated and induced to osteoclasts. It has been demonstrated that a single dose of 2 Gy may result in a significant loss of lumbar bone density at 3 days post­irradiation, however this is restored at 30 days post­irradiation. In the 3x8 Gy irradiation rat model, there was a rapid decrease in the aBMD of lumbar spine at 3 days and at 7 days post­irradiation, and the aBMD decline persisted even at 60 days post­irradiation. In addition, microCT analysis revealed a persistent decline in bone volume and damage in microarchitecture in the 3x8 Gy irradiation model, accompanied by a decrease in MAR, index of the decline in bone­forming ability. In the cellular mechanism, a single 2 Gy local irradiation mainly manifested as an enhancement of the BMMs osteoclastogenesis potential, which was different from the osteoclastogenesis inhibition after high­dose focal irradiation (3x8 Gy). In summary, the irradiation with simulated clinical focal fractionated radiotherapy exerts short­ and long­term systemic injury on bone tissue, characterized by different osteoclastogenesis potential between the high dose mode and a single 2 Gy focal irradiation. Physicians must consider the irreversibility of bone damage in clinical radiotherapy.

Photobiomodulation by a 635nm Diode Laser on Peri-Implant Bone: Primary and Secondary Stability and Bone Density Analysis-A Randomized Clinical Trial.

INTRODUCTION: Various procedures in dental implantology are performed to enhance the bone healing process and implant stability. One of these methods can be a low-level laser therapy (LLLT). OBJECTIVES: The aim of our study was to evaluate the stabilization (primary and secondary) and bone density in peri-implant zone after LLLT protocol using a 635 nm diode laser. MATERIAL AND METHODS: The research included 40 implants placed in the posterior region of a mandible in 24 patients (8 women and 16 man; age: 46.7 ± 8.7 years). The patients were randomly divided into 2 groups G1 (n=12, 18 implants) and G2 (n=12, 22 implants) according to the treatment procedure; G1 (test): 635 nm laser, with handpiece diameter: 8mm, output power: 100mW, spot area: 0.5024cm2, average power density: 199.04mW/cm2, continuous mode, dose: 4J per point (8J/cm2), time: 40 sec per point, 2 points (irradiation on a buccal and a lingual side of the alveolus/implant), and total energy per session 8J; G2 (control): no laser irradiation. The G1 (test) group's implants were irradiated according to the following protocol: 1 day before surgery, immediately after the surgery and 2, 4, 7, and 14 days after. The total energy after all therapeutic sessions was 48J. The implants stability was measured employing a Periotest device (Periotest Test Value: PTV) (measured immediately after the surgery, 7 days, 2 weeks, 4 weeks, and 2 and 3 months after the surgery) and the bone density using cone-beam computed tomography (grayscale value) (measured immediately after the surgery, 4 weeks and 12 weeks after the treatment). RESULTS: The average implant stability at different time points showed lower PTV value (higher stability) at 2nd and 4th week after 635 nm laser irradiation (G1) compared with a control (G2) group (p<0.01). The secondary stability of the implants after 12 weeks observation was not significantly higher for the laser group in contrast to none-irradiated implants (p>0.05). The mean grayscale value at the apical, middle, and cervical level of the titanium implants showed the reduction of pixel grayscale value after 2 weeks and was lower for the G1 group in contrast to the G2 group (p<0.01). The value of grayscale after 12 weeks was significantly higher at the middle and apical level of the implants in the G1group in contrast to the G2 group (p<0.01). CONCLUSION: The application of the 635 nm diode laser enhanced secondary implant stability and bone density. However, to assess the impact of the LLLT on peri-implant bone with different bone densities, further well-controlled long-term trials on larger study groups are needed.

Pulsed electromagnetic fields promote bone formation by activating the sAC-cAMP-PKA-CREB signaling pathway.

The application of pulsed electromagnetic fields (PEMFs) in the prevention and treatment of osteoporosis has long been an area of interest. However, the clinical application of PEMFs remains limited because of the poor understanding of the PEMF action mechanism. Here, we report that PEMFs promote bone formation by activating soluble adenylyl cyclase (sAC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) signaling pathways. First, it was found that 50 Hz 0.6 millitesla (mT) PEMFs promoted osteogenic differentiation of rat calvarial osteoblasts (ROBs), and that PEMFs activated cAMP-PKA-CREB signaling by increasing intracellular cAMP levels, facilitating phosphorylation of PKA and CREB, and inducing nuclear translocation of phosphorylated (p)-CREB. Blocking the signaling by adenylate cyclase (AC) and PKA inhibitors both abolished the osteogenic effect of PEMFs. Second, expression of sAC isoform was found to be increased significantly by PEMF treatment. Blocking sAC using sAC-specific inhibitor KH7 dramatically inhibited the osteogenic differentiation of ROBs. Finally, the peak bone mass of growing rats was significantly increased after 2 months of PEMF treatment with 90 min/day. The serum cAMP content, p-PKA, and p-CREB as well as the sAC protein expression levels were all increased significantly in femurs of treated rats. The current study indicated that PEMFs promote bone formation in vitro and in vivo by activating sAC-cAMP-PKA-CREB signaling pathway of osteoblasts directly or indirectly.

Denosumab versus zoledronic acid for preventing symptomatic skeletal events in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer: an outcome analyses with a mean follow-up of 3 years.

BACKGROUND: The purpose of this study was to evaluate the efficacy of denosumab or zoledronic acid (ZA) using symptomatic skeletal events (SSEs) as the primary endpoint in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer. METHODS: Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer receiving subcutaneous denosumab 120 mg Q4W, or intravenous ZA 4 mg Q4W until the primary analysis cut-off date were retrospectively analysed in the Hong Kong Practice-Based Cancer Research Center(HKCRC) from March 2011 to March 2013. The time to first on-study SSE that was assessed either clinically or through routine radiographic scans was the primary endpoint. RESULTS: 242 patients received denosumab or ZA treatment (n = 120, mean age of 64.9 years (SD 3.01) and n = 122, 65.4 years (3.44), respectively). The median times to first on-study SSE were 14.7 months (12.9-45.6) and 11.7 months (9.9-45.6) for denosumab and ZA, respectively (hazard ratio, HR 0.44, 95% CI 0.71-2.95; p = 0·0002). Compared with the ZA group, denosumab-treated patients had a significantly delayed time to first SSE (HR 0.65 [95% CI 0.29-1.45], p < 0.0001). An increased incidence of SSE was found in the 16-month follow-up with rates of 2.1 and 10.7% for denosumab and ZA, respectively (P = 0.033). The difference persisted with time with rates of 8.3 and 17.2% at the final follow-up, respectively (P < 0.05). CONCLUSION: In postmenopausal women aged ≥60 years with oestrogen-receptor-positive advanced breast cancer, denosumab significantly reduced the risk of developing SSEs compared with ZA. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.

Pulsed electromagnetic fields prevented the decrease of bone formation in hindlimb-suspended rats by activating sAC/cAMP/PKA/CREB signaling pathway.

Microgravity is one of the main threats to the health of astronauts. Pulsed electromagnetic fields (PEMFs) have been considered as one of the potential countermeasures for bone loss induced by space flight. However, the optimal therapeutic parameters of PEMFs have not been obtained and the action mechanism is still largely unknown. In this study, a set of optimal therapeutic parameters for PEMFs (50 Hz, 0.6 mT 50% duty cycle and 90 min/day) selected based on high-throughput screening with cultured osteoblasts was used to prevent bone loss in rats induced by hindlimb suspension, a commonly accepted animal model to simulate the space environment. It was found that hindlimb suspension for 4 weeks led to significant decreases in femoral and vertebral bone mineral density (BMD) and their maximal loads, severe deterioration in bone micro-structure, and decreases in levels of bone formation markers and increases in bone resorption markers. PEMF treatment prevented about 50% of the decreased BMD and maximal loads, preserved the microstructure of cancellous bone and thickness of cortical bone, and inhibited decreases in bone formation markers. Histological analyses revealed that PEMFs significantly alleviated the reduction in osteoblast number and inhibited the increase in adipocyte number in the bone marrow. PEMFs also blocked decreases in serum levels of parathyroid hormone and its downstream signal molecule cAMP, and maintained the phosphorylation levels of protein kinase A (PKA) and cAMP response element-binding protein (CREB). The expression level of soluble adenylyl cyclases (sAC) was also maintained. It therefore can be concluded that PEMFs partially prevented the bone loss induced by weightless environment by maintaining bone formation through signaling of the sAC/cAMP/PKA/CREB pathway. Bioelectromagnetics. 39:569-584, 2018. © 2018 Wiley Periodicals, Inc.

The effects of ultraviolet supplementation to the artificial lighting on rats' bone metabolism, bone mineral density, and skin.

Working and living under artificial lighting environment for a long duration do not allow sufficient sunlight exposure, resulting in an adverse effect on bone. Common artificial light source, white LED light, does not include ultraviolet irradiation that plays an important role in bone metabolism. Ultraviolet supplementation in artificial lighting environment can be used to simulate the effect of sunlight irradiation on bone metabolism. In this paper, we report the effects of long-term exposure of low-dose ultraviolet irradiation on the rats' bones and skin. We studied the changes in body weight, bone metabolism markers, bone mass content, bone mineral density, and skin of rats, under long-term exposure of low-dose ultraviolet irradiation. We found that the rats exposed to ultraviolet irradiation showed an increase in bone formation rate, decrease in bone resorption rate, and improvement in bone mass content and bone mineral density without adverse effects on skins. This paper provides an effective basis for future application of LED light to create a healthier, safer, and more comfortable indoor lighting environment.

Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

What Is the Effect of High-dose Radiation on Bone in Patients With Sacral Chordoma? A CT Study.

BACKGROUND: Effects of high-dose radiation using protons and photons on bone are relatively unexplored, but high rates of insufficiency fractures are reported, and the causes of this are incompletely understood. Imaging studies with pre- and postradiation scans can help one understand the effect of radiation on bone. QUESTIONS/PURPOSES: The purpose of this study was to assess the effects of high-dose radiation on the trabecular density of bone in the sacrum using CT-derived Hounsfield units (HU). METHODS: Between 2009 and 2015, we treated 57 patients (older then 18 years) with sacral chordoma. Fourteen (25%) of them were treated with radiation only. The general indication for this approach is inoperability resulting from tumor size. Forty-two (74%) patients were treated with transverse sacral resections and high-dose radiotherapy (using either protons or photons or a combination) before surgery and after surgery. During this time period, our indication for this approach generally was symptomatic sacral chordoma in which resection would prevent further growth and reasonable sacrifice of nerve roots was possible. Of those patients, 21 (50%) had CT scans both before and after radiation treatment. We used HU as a surrogate for bone density. CT uses HU to derive information on tissue and bone quantity. A recent study presented reference HU values for normal (mean 133 ± 38 HU), osteoporotic (101 ± 25 HU), and osteopenic bone (79 ± 32 HU). To adjust for scanning protocol-induced changes in HU, we calculated the ratio between bone inside and outside the radiation field rather than using absolute values. To assess the effect of radiation, we tested whether there was a difference in ratio (sacrum/L1) before and after radiation. A control measurement was performed (L2/L1) and also tested for a difference before and after radiation. Statistical analyses were performed using the paired t-test. RESULTS: The effects of radiation appeared confined to the intended field, because the bone density outside the treated field was not observed to decrease. The ratio of HU (a surrogate for bone density) in L2 relative to L1 did not change after radiotherapy (preradiation mean: 0.979 ± 0.009, postradiation mean: 0.980 ± 0.009, mean difference outside the radiation field: -0.001, 95% confidence interval [CI], -0.009 to 0.007, p = 0.799). The ratio of HU within the radiation field relative to L1 decreased after radiotherapy (preradiation mean: 0.895 ± 0.050, postradiation mean: 0.658 ± 0.050, mean difference inside the radiation field: 0.237, 95% CI, 0.187-0.287, p < 0.001), suggesting the bone density stayed the same outside the radiation field but decreased inside the radiation field. CONCLUSIONS: Trabecular bone density decreased after high-dose radiation therapy in a small group of patients with sacral chordoma. High-dose radiation is increasingly gaining acceptance for treating sacral malignancies; further long-term prospective studies using calibrated CT scanners and preferably bone biopsies are needed. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Long-Term Effect of Pulsed Nd-YAG Laser Combined with Exercise on Bone Mineral Density in Men with Osteopenia or Osteoporosis: 1 Year of Follow-Up.

BACKGROUND: A pulsed Nd-YAG laser is an effective physiotherapy modality used as a class IV high-intensity laser therapy (HILT). OBJECTIVE: The aim of this study is to investigate the efficacy of HILT alone or combined with exercise (HILT+EX) on bone mineral density (BMD) after 24 weeks and at 1 year of follow-up in men with osteopenia or osteoporosis. METHODS: One hundred men with osteopenia or osteoporosis (mean age, 53.78 [2.89] years; weight, 80.56 [7.33] kg; height 175 [5.30] cm) participated in the study. The T-scores were ≤-1.5. Patients were randomly assigned to four groups: HILT+EX (group I), placebo laser plus exercise (PL+EX; group II), HILT alone (HILT; group III), and PL (group IV). HILT was applied to the lower back and hip regions. Aerobic, weight-bearing, flexibility, strengthening, and balance exercises were performed three times per week for 24 weeks. The measured outcomes were BMD of the L2-L4 spine and total hip. Measurements were taken before and after 24 weeks and at 1 year of follow-up. RESULTS: Lumbar and total hip BMD significantly increased post-treatment in the HILT+EX and PL+EX groups, but insignificantly in the HILT and PL groups. HILT+EX showed a significantly greater effect than PL+EX did on lumbar BMD, with no significant difference in total hip BMD, after 24 weeks and at follow-up. CONCLUSIONS: Although HILT alone did not effectively increase lumbar and total hip BMD, HILT combined with exercise was more effective than exercise alone at increasing lumbar BMD after 24 weeks of treatment, with effects lasting up to 1 year.

EVALUATION OF BONE MINERALIZATION BY COMPUTED TOMOGRAPHY IN WILD AND CAPTIVE EUROPEAN COMMON SPADEFOOTS (PELOBATES FUSCUS), IN RELATION TO EXPOSURE TO ULTRAVIOLET B RADIATION AND DIETARY SUPPLEMENTS.

Captive rearing programs have been initiated to save the European common spadefoot (Pelobates fuscus), a toad species in the family of Pelobatidae, from extinction in The Netherlands. Evaluating whether this species needs ultraviolet B (UVB) radiation and/or dietary supplementation for healthy bone development is crucial for its captive management and related conservation efforts. The bone mineralization in the femurs and the thickest part of the parietal bone of the skulls of European common spadefoots (n = 51) was measured in Hounsfield units (HUs) by computed tomography. One group, containing adults (n = 8) and juveniles (n = 13), was reared at ARTIS Amsterdam Royal Zoo without UVB exposure. During their terrestrial lifetime, these specimens received a vitamin-mineral supplement. Another group, containing adults (n = 8) and juveniles (n = 10), was reared and kept in an outdoor breeding facility in Münster, Germany, with permanent access to natural UVB light, without vitamin-mineral supplementation. The HUs in the ARTIS and Münster specimens were compared with those in wild specimens (n = 12). No significant difference was found between the HUs in the femurs of both ARTIS and Münster adults and wild adults (P = 0.537; P = 0.181). The HUs in the skulls of both captive-adult groups were significantly higher than in the skulls of wild specimens (P = 0.020; P = 0.005). The HUs in the femurs of the adult ARTIS animals were significantly higher than the HUs in the femurs of the adult Münster animals (P = 0.007). The absence of UVB radiation did not seem to have a negative effect on the bone development in the terrestrial stage. This suggests that this nocturnal, subterrestrial amphibian was able to extract sufficient vitamin D3 from its diet and did not rely heavily on photobiosynthesis through UVB exposure.

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 intervention initiation timing of pulsed electromagnetic field on ovariectomy-induced osteoporosis in rats.

The aim of this study is to explore the effect of timing of initiation of pulsed electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and biomechanical properties, and to investigate receptor activator of NF-kB (RANK) expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were randomly divided into two equal batches of three groups each (10 rats in each group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized (OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12 group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced deterioration in bone mineral density (BMD) and mechanical properties in lumbar vertebral body and femur, and deterioration in bone microarchitecture in lumbar vertebral body and proximal tibia. Late PEMF intervention only inhibited deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar vertebral body. Both early and late PEMF therapy suppressed RANK protein expression in OVX rats without a concomitant effect on RANK mRNA expression. These results demonstrate that timing of initiation of PEMF therapy plays an important role in achieving optimal beneficial effects. The specific PEMF parameters may exert these favorable biological responses, at least partially, via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465, 2017. © 2017 Wiley Periodicals, Inc.

Effects of combined treatment with ibandronate and pulsed electromagnetic field on ovariectomy-induced osteoporosis in rats.

Ibandronate (IBN) and pulsed electromagnetic field (PEMF) have each shown positive effects for treating osteoporosis, but no study has evaluated the relative effects of these treatments combined. This study investigated the effects of IBN + PEMF on bone turnover, mineral density, microarchitecture, and biomechanical properties in an ovariectomized (OVX) rat model of osteoporosis. Fifty 3-month-old rats were randomly apportioned to receive a sham-operation (n = 10), or ovariectomy (n = 40). The latter group was equally divided as the model (OVX control) or to receive IBN, PEMF, or IBN + PEMF. Beginning the day after surgery, the IBN and IBN + PEMF groups received weekly subcutaneous IBN; the PEMF and IBN + PEMF groups were given daily PEMF during the same 12 weeks. After 12 weeks of treatments, biochemical parameters, bone mineral density (BMD), microarchitecture parameters, biomechanical properties, and some metabolic modulators that are involved in bone resorption were compared. The L5 lumbar vertebral body BMDs of the IBN, PEMF, and IBN + PEMF groups were 121.6%, 119.5%, and 139.6%; maximum loads were 111.4%, 112.7%, and 121.9%; and energy to failure was 130.8%, 129.2%, and 154.9% of the OVX model, respectively. The IBN + PEMF group had significantly lower levels of serum tartrate-resistant acid phosphatase 5b, and greater improvement in BMD, bone microarchitecture, and strength of the lumbar spine compared with monotherapy groups. Results showed that IBN + PEMF had a more favorable effect on the lumbar spine in this osteoporosis model than did either monotherapy. Bioelectromagnetics. 38:31-40, 2017. © 2016 Wiley Periodicals, Inc.

Effects of electromagnetic fields on bone loss in hyperthyroidism rat model.

Optimal therapeutics for hyperthyroidism-induced osteoporosis are still lacking. As a noninvasive treatment, electromagnetic fields (EMF) have been proven to be effective for treating osteoporosis in non-hyperthyroidism conditions. We herein systematically evaluated the reduced effects of EMF on osteoporosis in a hyperthyroidism rat model. With the use of Helmholtz coils and an EMF stimulator, 15 Hz/1 mT EMF was generated. Forty-eight 5-month-old male Sprague-Dawley rats were randomly divided into four different groups: control, levothyroxine treated (L-T4), EMF exposure + levothyroxine (EMF + L-T4), and EMF exposure without levothyroxine administration (EMF). All rats were treated with L-T4 (100 mg/day) except those in control and EMF groups. After 12 weeks, the results obtained from bone mineral density analyses and bone mechanical measurements showed significant differences between L-T4 and EMF + L-T4 groups. Micro CT and bone histomorphometric analyses indicated that trabecular bone mass and architecture in distal femur and proximal tibia were augmented and restored partially in EMF + L-T4 group. In addition, bone thyroid hormone receptors (THR) expression of hyperthyroidism rats was attenuated in EMF + L-T4 group, compared to control group, which was not observed in L-T4 group. According to these results, we concluded that 15 Hz/1 mT EMF significantly inhibited bone loss and micro architecture deterioration in hyperthyroidism rats, which might occur due to reduced THR expression caused by EMF exposure. Bioelectromagnetics. 38:137-150, 2017. © 2016 Wiley Periodicals, Inc.

Low-level laser therapy associated to a resistance training protocol on bone tissue in diabetic rats.

OBJECTIVE: The present study aimed to evaluate the in vivo response of a resistance training and low-level laser therapy (LLLT) on tibias and femurs of rats with diabetes mellitus (DM). MATERIALS AND METHODS: Forty male Wistar rats were randomly distributed into four experimental groups: control group (CG), diabetic group (DG), diabetic trained group (TG) and diabetic trained and laser irradiated group (TLG). DM was induced by streptozotocin (STZ) and after two weeks laser and resistance training started, performed for 24 sessions, during eight weeks. At the end of the experiment, animals were euthanized and tibias and femurs were removed for analysis. Histological, histomorphometrical, immunohistochemistry and mechanical analyses were performed. RESULTS: Trained groups, with or without laser irradiation, showed increased cortical area, bone density and biomechanical properties. The immunohistochemical analysis revealed that TG and TLG demonstrated an increased RUNX2 expression. RANK-L immunoexpression was similar for all experimental groups. CONCLUSION: In conclusion, it can be suggested that the resistance exercise program stimulated bone metabolism, culminating in increased cortical tibial area, bone mineral content, bone mineral density and biomechanical properties. Furthermore, the association of physical exercises and LLLT produced higher values for bone mineral content and stiffness. Consequently, these data highlight the potential of physical exercise in the management of bone loss due to DM and the possible extra osteogenic stimulus offered by lasertherapy. Further long-term studies should be carried out to provide additional information.