The periosteum is now widely recognized as a homeostatic and therapeutic target for actions of sex steroids and intermittent PTH administration. The mechanisms by which estrogens suppress but PTH promotes periosteal expansion are not known. In this report, we show that intermittent PTH(1-34) promotes differentiation of periosteal osteoblast precursors as evidenced by the stimulation of the expression or activity of alkaline phosphatase as well as of targets of the bone morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17beta-estradiol (E2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced differentiation of primary periosteal osteoblast progenitors. Administration of intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP-2 target Smad1/5/8 in the periosteum. A replacement dose of E2 had no effect by itself but suppressed PTH-induced phosphorylation of Smad1/5/8. In contrast to its effects to stimulate periosteal osteoblast differentiation, PTH promoted and subsequently suppressed proliferation of periosteal osteoblast progenitors in vitro and in vivo. E2 promoted proliferation and attenuated the antiproliferative effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis induced by various proapoptotic agents. These observations suggest that the different effects of PTH and estrogens on the periosteum result from opposing actions on the recruitment of early periosteal osteoblast progenitors. Intermittent PTH promotes osteoblast differentiation from periosteum-derived mesenchymal progenitors through ERK-, BMP-, and Wnt-dependent signaling pathways. Estrogens promote proliferation of early osteoblast progenitors but inhibit their differentiation by osteogenic agents such as PTH or BMP-2.

Preventive application of heparinoid moisturizer from the first day of WBRT significantly increased water content and helped to improve skin desquamation and dryness compared with no treatment.

ObjectiveThe effect of heparinoid moisturizer use after acute skin damage for patients receiving whole-breast radiotherapy after lumpectomy is understudied.MethodsA total of 30 patients were randomly assigned to receive heparinoid moisturizer (Group M), and 32 patients comprised the control group (Group C). Patients in Group M were instructed to apply heparinoid moisturizer from 2 weeks following whole-breast radiotherapy, and to continue to use the moisturizer until 3 months after completion of whole-breast radiotherapy. Group C patients were instructed to not apply any topical moisturizer during the study period. The relative ratio of skin water content ratio (RWCR(t) = (It /Nt)/(I0/N0)) between irradiated and non-irradiated field was calculated. Signs and symptoms were also assessed. The primary endpoint was the difference in relative ratio of skin water content ratio between 2 and 4 weeks following whole-breast radiotherapy.ResultsIn Group C, relative ratio of skin water content ratio dropped to 0.80 ± 0.15 at 2 weeks and maintained the low level at 4 weeks following whole-breast radiotherapy. Similarly, in Group M, relative ratio of skin water content ratio dropped to 0.81 ± 0.19 at 2 weeks (prior to application), however, it returned to baseline level (1.05 ± 0.23) at 4 weeks (2 weeks after application). The arithmetic difference of relative ratio of skin water content ratio in Group M was 0.24 ± 0.23 and was significantly larger than in Group C (0.06 ± 0.15; P < 0.01). Skin dryness and desquamation were less severe in Group M.ConclusionsThe application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy significantly increased water content and helped improve skin dryness and desquamation compared with no use of moisturizer.

PurposeThe purpose of this study was to quantify the target coverage, homogeneity, and robustness of the dose distributions against geometrical uncertainties associated with four whole breast radiotherapy techniques.MethodsThe study was based on the planning-computed tomography-datasets of 20 patients who underwent whole breast radiotherapy. A total of four treatment plans (wedge, field-in-field [FIF], hybrid intensity-modulated radiotherapy [IMRT], and full IMRT) were created for each patient. The hybrid IMRT plans comprised two opposed tangential open beams plus two IMRT beams. Setup errors were simulated by moving the beam isocenters by 5 mm in the anterior or posterior direction.ResultsWith the original plan, the wedge technique yielded a high volume receiving ≥107% of the prescription dose (V107; 7.5%±4.2%), whereas the other three techniques yielded excellent target coverage and homogeneity. A 5 mm anterior displacement caused a large and significant increase in the V107 (+5.2%±4.1%, p<0.01) with the FIF plan, but not with the hybrid IMRT (+0.4%±1.2%, p=0.11) or full IMRT (+0.7%±1.8%, p=0.10) plan. A 5-mm posterior displacement caused a large decrease in the V95 with the hybrid IMRT (-2.5%±3.7%, p<0.01) and full IMRT (-4.3%±5.1%, p<0.01) plans, but not with the FIF plan (+0.1%±0.7%, p=0.74). The decrease in V95 was significantly smaller with the hybrid IMRT plan than with the full IMRT plan (p<0.01).ConclusionThe FIF, hybrid IMRT, and full IMRT plans offered excellent target coverage and homogeneity. Hybrid IMRT provided better robustness against geometrical uncertainties than full IMRT, whereas FIF provided comparable robustness to that of hybrid IMRT.