Low energy availability reduces bone mass and gonadal function in male mice.

INTRODUCTION: In women, the female athlete triad, marked by low energy availability, functional hypothalamic amenorrhea and osteoporosis, is a recognized risk for stress fractures. Stress injuries also occur in men, but by contrast risks and mechanisms underlying them are less characterized. MATERIALS AND METHODS: 5 week-old wild-type male mice were fed ad libitum (ad) or subjected to 60% food restriction (FR) for five weeks. In both groups, some mice were allowed access to an exercise wheel in cages to allow voluntary wheel running (ex) and/or treated with active vitamin D analogues. Mice were sacrificed and analyzed at 10 weeks of age. RESULT: Male FR mice exhibited significantly reduced testicle weight, serum testosterone levels and bone mass. Such bone losses in FR male mice were enhanced by exercise. Histological analysis revealed that both bone-resorbing and -forming activities were significantly reduced in FR or FR plus exercise (FR + ex) mice, mimicking a state of low bone turnover. Significantly reduced bone mass in FR or FR + ex male mice was significantly rescued by treatment with active vitamin D analogues, with significant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which is critical for bone remodeling, were significantly lower in FR versus control male mice. CONCLUSIONS: Low energy availability puts men at risk for stress injuries as well, and low energy availability is upstream of gonadal dysfunction and osteoporosis in males. Active vitamin D analogues could serve as therapeutic or preventive options for stress injuries in men.

Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice.

Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

Food restriction reduces cortical bone mass and serum insulin-like growth factor-1 levels and promotes uterine atrophy in mice.

Low energy availability in female athletes often causes hypothalamic amenorrhea and osteoporosis, in turn promoting stress fractures. Mechanisms underlying these conditions remain unclear. Here we show that model mice subjected to food restriction (FR) or FR-plus-voluntary running exercise exhibit significantly reduced bone mineral density, cortical bone parameters and uterine weight than do control mice, and that these parameters worsen in the FR-plus-exercise group. Relative to controls, FR and FR-plus-exercise groups showed significantly lower mineral apposition rate and osteoclast number and significantly reduced serum insulin-like growth factor-1 (IGF1) levels. Outcomes were rescued by ED71 or 1.25(OH)2D3 treatment. Thus, we conclude that administration of active vitamin D analogues represents a possible treatment to prevent these conditions.

Technical note: development and testing of a radio transmission pH measurement system for continuous monitoring of ruminal pH in cows.

An indwelling ruminal pH system has been used for the continuous recording of ruminal pH to evaluate subacute ruminal acidosis (SARA) in dairy cows. However this system does not allow the field application. The objective of this study was to develop a new radio transmission pH measurement system, and to assess its performance and usefulness in a continuous evaluation of ruminal pH for use on commercial dairy farms. The radio transmission pH measurement system consists of a wireless pH sensor, a data measurement receiver, a relay unit, and a personal computer installed special software. The pH sensor is housed in a bullet shaped bolus, which also encloses a pH amplifier circuit, a central processing unit (CPU) circuit, a radio frequency (RF) circuit, and a battery. The mean variations of the measurements by the glass pH electrode were +0.20 (n=10) after 2 months of continuous recording, compared to the values confirmed by standard pH solutions for pH 4 and pH 7 at the start of the recording. The mean lifetime of the internal battery was 2.5 months (n=10) when measurements were continuously transmitted every 10 min. Ruminal pH recorded by our new system was compared to that of the spot sampling of ruminal fluid. The mean pH for spot sampling was 6.36 ± 0.55 (n=96), and the mean pH of continuous recording was 6.22 ± 0.54 (n=96). There was a good correlation between continuous recording and spot sampling (r=0.986, P<0.01). We also examined whether our new pH system was able to detect experimentally induced ruminal acidosis in cows and to record long-term changes in ruminal pH. In the cows fed acidosis-inducing diets, the ruminal pH dropped markedly during the first 2h following the morning feeding, and decreased moreover following the evening feeding, with many pulse-like pH changes. The pH of the cows showed the lowest values of 5.3-5.2 in the midnight time period and it recovered to the normal value by the next morning feeding. In one healthy periparturient cow, the circadian changes in ruminal pH were observed as a constant pattern in the pre-parturient period, however that pattern became variable in the post-partum period. The frequency of the ruminal pH lower than 5.5 increased markedly 3 and 4 days after parturition. We demonstrated the possible application of a radio transmission pH measurement system for the assessment and monitoring of the ruminal pH of cows. Our new system might contribute to accurate assessment and prevention of SARA.

Self-inflicted splenic injury in snowboarders: postural analysis of forward falls of 10 consecutive patients.

Splenic injuries are often caused when snowboarders thrust their abdomens with their own left elbows after falling and hitting the ground. We report 10 snowboarders who suffered a splenic injury by accidentally thrusting their own elbow against their abdomen upon falling to the ground. Clinical presentation, postural analysis, and treatment are described. In an attempt to break the force while falling, snowboarders assumed 1 of 2 defensive postures that subsequently induced splenic injury: falling with an outstretched hand or falling with folded arms placed closely to the chest, that is, the fetal tuck posture. Snowboarders who fell in the outstretched hand posture developed more severe symptoms than those who fell in the fetal tuck posture. Herein, we discuss the mechanisms of such snowboarding-related splenic injury in detail and provide a review of the literature.