Abstract: To evaluate obstetric predictors of umbilical cord plasma AVP levels, serum TSH levels and the timing of first voiding, 87 singleton term newborns were divided into three groups: group A, vaginal delivery (n = 30); group B, cesarean section (CS) during labor (n = 26); and group C, elective CS (n = 31). The AVP concentration was 120 (0.7-2170) ng/L in group A, 1.8 (0.01-183) ng/L in group B, and 0.8 (0.01-30) ng/L in group C (p < 0.001). In group A, the TSH concentration was 10.20 (3.5-30.80) mU/L; in group B, 5.40 (2.10-43.00) mU/L; and in group C, 5.30 (2.90-11.00) mU/L (p = 0.001). Duration of labor had a positive correlation with AVP (p < 0.001) and TSH (p = 0.001) concentrations. The timing of first voiding had a positive correlation with gestational age (p = 0.003), volume of additional feeding before first voiding (p < 0.001), and umbilical AVP concentration (p = 0.023). The AVP and TSH concentrations are associated with mode of delivery and duration of labor and AVP levels also with the timing of first voiding in the newborn.

Abstract: Paricalcitol is a less hypercalcemic vitamin D analog that has been shown to suppress secondary hyperparathyroidism and to prevent the associated histomorphometric changes in bone. In this study, we show that paricalcitol also ameliorates the renal insufficiency-induced loss of bone mineral and the mechanical competence of bone. INTRODUCTION: Renal bone disease is a common consequence of chronic renal insufficiency and the associated secondary hyperparathyroidism (SH). Paricalcitol [19-nor-1,25(OH)(2)D(2)] has been shown to ameliorate SH and prevent renal failure-induced histomorphometric changes in bone with minimal calcemic and phosphatemic activity. However, information about its efficacy on restoration of bone structural strength is lacking. In this study, we explored the effects of paricalcitol treatment on bone structure and strength in a model of advanced renal disease. MATERIALS AND METHODS: Forty-five 8-week-old rats were randomly assigned to either surgical 5/6 nephrectomy (NTX) or Sham-operation. After a 15-week postoperative disease progression period, the NTX rats were further allocated to uremic control (NTX) and treatment (NTX + paricalcitol) groups, the latter of which received paricalcitol for the subsequent 12 weeks. After 27 weeks, the animals were killed, plasma samples were collected, and both femora were excised for comprehensive analysis of the femoral neck and midshaft (pQCT and biomechanical testing). RESULTS: High mortality that exceeded 30% was observed in both NTX groups. NTX induced over a 13-fold increase in plasma PTH, whereas this increase was only 5-fold after paricalcitol treatment. At the femoral neck, NTX was associated with an 8.1% decrease (p < 0.05) in vBMD and a 16% decrease in breaking load (p < 0.05) compared with the Sham group, whereas paricalcitol treatment completely prevented these changes. At the femoral midshaft, the NTX resulted in a 6.6% decrease in cortical BMD (p < 0.01 versus Sham), and this change was also prevented by paricalcitol. CONCLUSIONS: Paricalcitol administration prevented renal insufficiency-associated decreases in BMD in the femoral neck and the femoral midshaft and restored bone strength in the femoral neck. Therefore, paricalcitol can efficiently ameliorate renal insufficiency-induced loss of bone mineral and mechanical competence of bone.

Abstract: To investigate the controversial issue whether exercise-induced positive effects on bone can be maintained after cessation of exercise, 100 5-week-old male Sprague-Dawley rats were used to assess the effects of long-term exercise (EX, treadmill running) and subsequent deconditioning (DC, free cage activity) on the femoral neck and femoral midshaft. At entry, the rats were randomly assigned into eight groups: four control groups (C14, C28, C42, and C56), and four exercise groups (EX, EX + DC14, EX + DC28, and EX + DC42). Rats in the exercise groups were first subjected to a 14-week period of progressively intensifying running, after which the rats of group EX were killed and the remaining exercise groups (EX + DC14, EX + DC28, and EX + DC42) were allowed to move freely in their cages for a subsequent deconditioning period of 14, 28, or 42 weeks, whereas control rats were kept free in their cages for the entire study period (0-56 weeks) and killed with their respective exercise group. At each time point, a comprehensive analysis of the femoral neck and midshaft characteristics (peripheral quantitative computed tomography analysis and fracture load [Fmax]) was performed. In comparison with their age-matched controls, 14 weeks of treadmill training resulted in significant (p < 0.05) increases in all measured femoral neck parameters of the growing male rats (i.e., +25% in total cross-sectional area [tCSA], +28% in total bone mineral content [tBMC], +11% in total bone mineral density [tBMD], and +30% in Fmax). On the contrary, no exercise-induced positive effects were seen in femoral midshaft. The exercise-induced benefits in the femoral neck were partially maintained during the deconditioning period of 14 weeks, the tCSA being + 17%, tBMC + 18% (both p < 0.05), and the Fmax + 11% (p = 0.066) higher in the exercised group than control group. However, after 42 weeks of deconditioning, these benefits were eventually lost. In conclusion, exercise through the period of the fastest skeletal growth results in significant improvements in size, mineral mass, and strength of the femoral neck of male rats. However, these exercise-induced bone benefits are eventually lost if exercise is completely ceased, and thus, continued training is probably needed to maintain the positive effects of youth exercise into adulthood. Further studies should focus on assessing the minimal level of activity needed to maintain the exercise-induced bone gains.

Abstract: Aged bones have been considered to have reduced capacity to respond to changes in incident loading. By subjecting young and adult rats to increased loading and subsequent deconditioning, we observed quantitatively similar adaptive responses of bone in these two groups, but young skeletons adapted primarily through geometric changes and adult bones through increased volumetric density. Loss of the exercise-induced bone benefits did not depend on age. INTRODUCTION: Aging has been shown to decrease the sensitivity of the mechanosensory cells of bones to loading-induced stimuli, presumably resulting in not only reduced capacity but also different adaptive mechanism of the aged skeleton to altered loading, as well as poorer capacity to preserve exercise-induced bone benefits. MATERIALS AND METHODS: Fifty young (5-week-old) and 50 adult (33-week-old) male rats were randomized into control and exercise (+deconditioning) groups. After a 14-week progressively intensified running program, one-half of the exercised rats (both young and adult) were killed, and the remaining rats underwent subsequent 14-week period of deconditioning (free cage activity). A comprehensive analysis of the femoral neck was performed using peripheral quantitative computed tomography and mechanical testing. RESULTS: In comparison with the controls, both young and adult exercised rats had significant increases in almost all measured parameters: +25% (p < 0.001) and +10% (not significant [NS]) in the cross-sectional area; +28% (p < 0.001) and +18% (p < 0.001) in bone mineral content; +11% (p < 0.05) and +23% (p < 0.001) in bone mineral density; and +30% (p < 0.01) and +28% (p < 0.01) in the breaking load, respectively. The skeletal responses were not statistically different between the young and adult rats. After the 14-week period of deconditioning, the corresponding exercised-to-controls differences were +17% (p < 0.05) and +10% (NS), +18% (p < 0.05) and +13% (p < 0.05), +2% (NS) and +2% (NS), and +11% (NS) and +6% (NS), respectively. Again, the response differences were not significant between the age groups. CONCLUSION: Quantitatively, the capacity of the young and adult skeleton to adapt to increased loading was similar, but the adaptive mechanisms appeared different: growing bones seemed to primarily display geometric changes (increase in bone size), whereas the adult skeleton responded mainly through an increase in density. Despite this apparent difference in the adaptive mechanism, aging did not modulate the ability of the skeleton to preserve the exercise-induced bone gain, because the bone loss was similar in the young and adult rats after cessation of training.

Abstract: To first test the possible effect of gender on the responsiveness of growing rat skeleton to mechanical loading, 5-week-old littermates of 25 male and 25 female rats were subjected to either free-cage activity or treadmill training for a period of 14 weeks (experiment 1). Using peripheral quantitative computed tomography (pQCT) and mechanical testing of the femoral neck, we observed female rats exhibiting a clearly lower responsiveness to external loading than male rats (+3.0% vs +25% in cross-sectional area (CSA), +4.2% vs +27% in the bone mineral content (BMC), -0.6% vs +10% in volumetric bone mineral density (BMD), and +4.7% vs +28% in fracture strength (F(max)) of the femoral neck). Also, relative to the mechanical demands placed on the skeleton, the bones of the young female rats were considerably denser (>50%) than those of the males. In the subsequent experiment 2, we repeated the above-noted first experiment with 33-week-old rats and observed virtually identical exercise-induced benefits (+2.1% vs +10% in CSA, +3.4% vs +18% in BMC, +2.5% vs +23% in BMD, and -1.1% vs +27% in F(max) in females vs males, respectively) and the growth/puberty-related condensation of mineral into female bones. Finally, in experiment 3, 60 littermates of 3-week-old female rats were first subjected to sham operation or ovariectomy and then further randomized to exercise or control groups, respectively, to study whether the condensation of mineral into female bones and their lower responsiveness to loading were attributable to the effects of estrogen. At the end of the 16-week intervention, our pQCT and mechanical testing analysis showed not only the anticipated effect of reduced bone density in the ovariectomized rats ( approximately -20%) but also the hypothesized better responsiveness to mechanical loading in these estrogen-depleted rats (-3.5% vs +9.1% in CSA, -0.4% vs +12% in BMC, +4.4% vs +9.6% in BMD, and -4.2% vs +16% in F(max) in SHAM vs OVX, respectively). In conclusion, the results of our series of three experiments suggest that as such estrogen seems to have very little primary effect on the sensitivity of female bone to respond to external loading, but rather deposits extra stock of mineral into female bones in puberty. This estrogen-driven extra condensation of the female skeleton seems to persist into adulthood, simultaneously damping the responsiveness of the female skeleton to mechanical loading.