MCF7 human breast cancer cells growing as multicellular spheroids were examined as a model of three-dimensional cellular organization. Estrogen-free medium inhibited spheroid formation. In medium containing estrogens, the antiestrogen hydroxytamoxifen decreased the spheroid growth rate. Analyses with the recursion formula after Gompertz fitting showed that the rate of exponential decrease in growth rate (alpha) was alpha 0.099 +/- 0.013 d-1, and the decrease in alpha' was 0.061 +/- 0.015 d-1 for 0.1 microM hydroxytamoxifen and control spheroids respectively. MCF7 cells which had been growth arrested in an estrogen-free medium showed a significant decrease in radiosensitivity (surviving fraction at 2 Gy, SF2 = 63%) when compared with 0.1 nM 17 beta-estradiol-treated cells (SF2 = 38%). No differences in radiosensitivity were seen in MCF7 spheroids in estrogen-supplemented medium (radiation dose necessary to control 50% of spheroids (SCD50) was 5.51 Gy; derived alpha, beta and SF2 were 0.301 +/- 0.110 Gy-1, 0.018 +/- 0.005 Gy-2, and 51% respectively) when compared with monolayer cultures in the same medium (alpha = 0.316 +/- 0.059 Gy-1, beta = 0.023 +/- 0.006 Gy-2 and SF2 = 50%). In the spheroid model, manipulating the cellular environment, i.e., with estrogen treatment, modulates sensitivity to ionizing radiation.

Alkaline phosphatase (ALP) deficiency has been linked to reduced physical performance, as seen in hypophosphatasia (HPP). However, its potential role in muscle function has not been fully explored. This was a cross-sectional study in 34 HPP adults and 34 matched healthy controls. Muscle strength was assessed using handgrip strength (HGS), considering values below the 10th percentile of the Spanish population as low strength. Muscle mass was evaluated using dual-energy X-ray absorptiometry and morphometric ultrasound. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and total hip. The prevalence of low muscle strength was significantly higher in the HPP group compared to controls (30% vs. 6%; p = 0.009), with decreased HGS in the HPP group (p = 0.039). Positive associations were observed between ALP and femoral neck BMD, leg circumference, and fat-free mass and an inverse association with tricipital skinfold. Subjects with serum ALP activity below the sex-adjusted median had a significantly higher risk of low muscle strength independently of HPP diagnosis. ALP remained independently associated with HGS (p = 0.005), and a predictive model using ALP values showed strong capability to predict low-muscle-strength risk. Based on these results, we conclude circulating ALP levels are independently associated with muscle strength and may represent a useful biomarker for the early detection of muscle dysfunction. Future longitudinal or interventional studies are needed to assess whether ALP plays a causal role in muscle strength.

Background: Cystic fibrosis-related bone disease (CFBD) is a comorbidity whose prevalence is increasing. Conventional areal DXA (aDXA) only assesses part of bone strength, whereas new techniques provide a more comprehensive assessment of bone structure. However, these tools are rarely implemented systematically. Furthermore, the contribution of clinical factors to bone structural parameters remains insufficiently characterized. Therefore, this study aimed to comprehensively assess cortical and trabecular bone alterations in adults with CF, and to explore clinical and lifestyle factors associated with bone health. Methods: A case–control study was conducted including 32 adults with CF and 70 healthy controls matched by age, sex, and BMI. Bone status was assessed using aDXA, trabecular bone score (TBS), and three-dimensional DXA (3D-DXA). Clinical data, body composition, lifestyle variables, and biochemical markers were collected. Multivariate linear regression models were applied to explore factors associated with bone parameters. Results: Twenty-two percent of CF people had prevalent fragility fractures and the percentage with low bone mass was significantly higher (28.1% vs. 5.7%; p < 0.001). TBS categories indicated more degraded microarchitecture in CF (p = 0.002). Cortical and trabecular 3D-DXA values were also significantly lower (p < 0.001). Adherence to the Mediterranean diet (MedDiet) was significantly associated with most of the bone parameters evaluated. Other variables associated with bone parameters included sex, fat-free and fat mass, prolonged corticosteroid use, intake of oral nutritional supplements, FEV₁, disease duration and P1NP-values. Conclusions: Adults with CF revealed significant cortical and trabecular structural deficits. Among the evaluated factors, adherence to MedDiet was associated with several bone parameters, suggesting a potential role of dietary patterns in CF bone health. Further studies are needed to confirm these preliminary results.