Modeling Space Radiation Induced Bone Changes in Rat Femurs through Finite Element Analysis.

As the duration of manned missions outside of the Earth's protective shielding increase, astronauts are at risk for exposure to space radiation. Various organ systems may be damaged due to exposure. This study investigates the bone strength changes using finite element modeling of Long Evans rats (n=85) subjected to graded, head-only proton (0, 10, 25, and 100 cGy, 150 MeV/n) and 28silicon (0, 10, 25, and 50 cGy, 300 MeV/n) radiation. The strength of the femoral neck will be examined due its clinical relevance to hip fractures. It has been shown in previous studies that bone mineral density was not reduced at the site of fracture. These findings question whether measurements of bone mineral density may be used to assess risk of hip fracture. The mechanisms leading to the irregular relationship between bone density and strength are still uncertain within literature and investigated to greater extent in clinical applications. Finite element analysis within this study simulated physiological loading of the femoral neck. No significant changes in femoral neck strength were found across doses of proton or 28silicon head-only radiation. Future work includes performing mechanical testing of the bone samples. Moving from mouse to larger animal models may also provide the increased lifespan for assessing the long-term outcomes of radiation exposure.

Early dose-dependent cortical thinning of the femoral neck in anal cancer patients treated with pelvic radiation therapy.

BACKGROUND AND PURPOSE: Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤4months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed. RESULTS: Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p<0.05). FN volume receiving ≥40Gy (V40Gy) was a significant predictor of focal cortical thinning ≥30% (p=0.03). A significant decrease in FN trBMD was observed (-6.4% [range -34.4 to 3.3%]; p=0.01). CONCLUSION: Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS.

Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.

Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial.

UNLABELLED: The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. INTRODUCTION: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. MATERIALS AND METHODS: We randomized women 55-80 years of age with femoral neck BMD T scores < or = -1.6 to alendronate (ALN), 5-10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score < or = -2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > -2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. RESULTS AND CONCLUSIONS: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover.

A comparison of skeletal chord-length distributions in the adult male.

In radiation protection, skeletal dose estimates are required for the tissues of the hematopoietically active bone marrow and the osteogenic cells of the trabecular and cortical endosteum. Similarly, skeletal radiation dose estimates are required in therapy nuclear medicine in order to develop dose-response functions for myelotoxicity where active bone marrow is generally the dose-limiting organ in cancer radioimmunotherapy. At the present time, skeletal dose models in both radiation protection and medical dosimetry are fundamentally reliant on a single set of chord-length distribution measurements performed at the University of Leeds in the late 1970's for a 44-y-old male subject. These distributions describe the relative frequency at which linear pathlengths are seen across both the marrow cavities and bone trabeculae in seven individual bone sites: vertebrae (cervical and lumbar), proximal femur (head and neck), ribs, cranium (parietal bone), and pelvis (iliac crest). In the present study, we present an alternative set of chord-length distribution data acquired within a total of 14 skeletal sites of a 66-y-old male subject. The University of Florida (UF) distributions are assembled via 3D image processing of microCT scans of physical sections of trabecular spongiosa at each skeletal site. In addition, a tri-linear interpolation Marching Cube algorithm is employed to smooth the digital surfaces of the bone trabeculae while chord-length measurements are performed. A review of mean chord lengths indicate that larger marrow cavities are noted on average in the UF individual for the cervical vertebrae (1,038 vs. 910 microm), lumbar vertebrae (1,479 vs. 1,233 microm), ilium (1,508 vs. 904 microm), and parietal bone (812 vs. 389 microm), while smaller marrow cavities are noted in the UF individual for the femoral head (1,043 microm vs. 1,157 microm), the femoral neck (1,454 microm vs. 1,655 microm), and the ribs (1,630 microm vs. 1,703 microm). The mean chord-lengths for the bone trabeculae show close agreement for both individuals in the ilium (approximately 240 microm) and cervical vertebrae (approximately 280 microm). Thicker trabeculae were seen on average in the UF individual for the femoral head (ratio of 1.50), femoral neck (ratio of 1.10), lumbar vertebrae (ratio of 1.29), and ribs (ratio of 1.14), while thinner trabeculae were seen on average in the UF individual for the parietal bone of the cranium (ratio of 0.92). In two bone sites, prominent discrepancies in chord distribution shape were noted between the Leeds 44-y-old male and the UF 66-y-old male: (1) the bone trabeculae in the ribs, and (2) the marrow cavities and bone trabeculae within the cranium.

Bilateral femoral neck fractures after pelvic irradiation.

Our patient, who had no history of trauma, developed bilateral femoral neck fractures several years after pelvic irradiation. The well-documented sequelae of femoral neck fractures include avascular necrosis, nonunion, and malunion. Postirradiation pelvic pain, particularly in the absence of trauma, should be aggressively evaluated. With high clinical suspicion and normal plain radiographs, MRI can be used to exclude potentially serious fractures.

[Osteoradionecrosis at the level of coxo-femoral articulation in the adult]. / Radionécrose au niveau de l'articulation coxofémorale chez l'adulte.

Two cases of either cervical or acetabular osteoradionecrosis were described. One patient had endoprosthetic replacement of the hip, the other did not receive any surgical treatment. Regarding the literature, osteoradionecrosis occurs in 0.3 to 4% of the irradiated bones. Histologically there is a destruction of the bone by direct toxicity of the radiation and by destruction of the vascular supply. The threshold of irreversible bone destruction is 30 Gy. Fractures are epiphenomenons of osseous radionecrosis. The diagnosis can be suspected either by radiographies or by bone scans. Sometimes a bone biopsy is necessary to differentiate between bone necrosis, bone metastasis and eventually a radiation-induced sarcoma of the bone. If the osteoradionecrosis affects the acetabulum, even in the case of a stress fracture without acetabular protrusion of the femoral head, no surgical treatment is recommended. Weight bearing is avoided and spontaneous resolution occurs in most cases. If, on the other hand, there is a fracture through the femoral neck, hemiarthroplasty or total joint replacement is the treatment of choice. Total joint replacement is also recommended in case of an extensive radiation induced coxopathy.