Skeletal effects of estrogen and mechanical loading are structurally distinct.

Estrogen has been suggested to influence skeletal homeostasis by both increasing the sensitivity of the feedback control system for skeletal rigidity and acting directly on bone surfaces. The objective of the present study was to explore the proposed interaction between the skeletal effects of estrogen and locomotion. Thirty 3-week-old littermates of female Sprague-Dawley rats were first randomly assigned into bilateral sham (E(+)) or ovariectomy (E(-)) surgery after which, the left hindlimb each study animal was cast immobilized (L(-)) while the right limb served as locomotively loaded control (L(+)), a classic 2x2 factorial study design. After 8-week study period, femoral neck, femur midshaft and distal metaphysis were analyzed by peripheral quantitative computed tomography (pQCT), microcomputed tomography (microCT), and mechanical testing. The loading-induced effects were virtually identical in the estrogen-replete (E(+)) and estrogen-deplete (E(-)) groups (Femoral neck: +78% vs. +69% in the tCSA, +74% vs. +55% in the tBMC, -6.0% vs. -7.2% in the tBMD, and +33% vs. +58% in the F(max); Femoral midshaft: +6.9% vs. +3.9% in the cCSA, +13% vs. +13% in the tCSA, +23% vs. +16% in the cBMC, +5.2% vs. +5.1% in the cBMD, and +8.0% vs. +8.0% in the F(max), respectively. All comparisons, NS), challenging the alleged modulatory effect of estrogen on skeletal mechanosensitivity. Estrogen did not have an independent effect on the periosteal apposition at any of the evaluated bone regions. Instead, according to its primary reproductive function, the effects of estrogen were restricted to accrual of bone mass only, the stimulus being apparent at the endosteal surface of cortex and trabecular structure of the distal metaphysis. In conclusion, the present results indicate that that the actions of estrogen and loading on bone structure are independent and additive in nature.

Paricalcitol [19-nor-1,25-(OH)2D2] in the treatment of experimental renal bone disease.

UNLABELLED: 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.

The bone gain induced by exercise in puberty is not preserved through a virtually life-long deconditioning: a randomized controlled experimental study in male rats.

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.

Femoral neck response to exercise and subsequent deconditioning in young and adult rats.

UNLABELLED: 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.

Decreased free water clearance is associated with worse respiratory outcomes in premature infants.

OBJECTIVE: The goal was to elucidate predictors of decreased free water clearance (DFWC) in very low birth weight (VLBW) infants. We hypothesized that DFWC and fluid retention are linked to the severity of pulmonary problems and prolonged respiratory support, especially to nCPAP treatment. METHODS: The investigation was carried out at Tampere University Hospital between 2001 and 2006. The study population comprised 74 VLBW infants born at 29.21 (24.57-34.14) weeks of gestation. Median birth weight was 1175 (575-1490) grams. We measured plasma and urine osmolality and 24-hour urine volume to calculate free water clearance (FWC) for each infant. If FWC was less than 30 ml/kg/day the infant was classified as having DFWC. RESULTS: There were 38 (51.4%) infants with DFWC in the study population. The median duration of the observed DFT period was 14 (4-44) days. The gestational age at birth was lower for DFWC infants compared to infants with normal FWC (NFWC), 28.29 (24.57-32.86) vs. 30.00 (25.57-34.14) weeks (p = 0.001). DFWC infants also needed longer ventilator treatment, 2 (0-23) vs. 0.50 (0-23) days (p = 0.046), nCPAP treatment 30 (0-100) vs. 3 (0-41) days (p<0.0001) and longer oxygen supplementation 47 (0-163) vs. 22 (0-74) days (p = 0.011) than NFWC infants. All values presented here are medians with ranges. CONCLUSIONS: DFWC appears to be frequently connected with exacerbation and prolongation of pulmonary problems in VLBW infants. Cautious fluid administration seems to be indicated in VLBW infants with prolonged respiratory problems and DFWC.

Predictors of delayed first voiding in newborn.

AIM: Delay>24 h of age in neonates' first voiding attracts attention, although the phenomenon is usually benign. Earlier studies indicate that stress increases the infant's arginine vasopressin (AVP) and aldosterone secretion during birth. Our aim was to seek predictors of delayed first voiding and indirect evidence of AVP effect behind this phenomenon. METHODS: The study population comprised 20 normal-term newborns whose first voiding was delayed>24 h of age (cases), and 19 age-matched control infants who voided for the first time at <24 h of age (controls). The first urine was collected and osmolality (U-Osm) and sodium content (U-Na) measured. RESULTS: The median of U-osm in cases was 432.50 (284-519) and in controls 337.50 (169-497) mOsm/L (p=0.005), and U-Na 21.50 (9-241) and 40.00 (13-226) mmol/L (p=0.001), respectively. Cases were more frequently born to primiparous mothers than controls (70% vs. 21%, p=0.004). Duration of labour was longer in cases than controls, first stage 10.5 h (3.92-20.50 h) versus 5.7 h (1.17-16.00 h) (p=0.045) and second stage 0.42 h (0.08-1.25 h) versus 0.17 h (0.08-0.92 h) (p=0.015). All seven (35%) abnormal cardiotocographies were recorded with cases (p=0.008). CONCLUSIONS: Delayed voiding appears to be related to a prolonged and stressful birth. Laboratory findings in the first urine suggest increased AVP and aldosterone secretion in such cases.

Predictors of AVP and TSH levels and the timing of first voiding in the newborn.

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.