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

Abstract

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. Here we propose that low energy availability puts men at risk for stress injuries as well. Male low energy availability model mice, established by limiting food intake, exhibited signi cantly reduced testicle weight, serum testosterone levels and bone mass. Such losses in bone mass were enhanced by exercise in food-restricted (FR) male mice. Histological analysis revealed that both bone-resorbing and -forming activities were signi cantly reduced in FR or FR plus exercise (FR+ex) mice, mimicking a state of low bone turnover. Signi cantly reduced bone mass in FR or FR+ex male mice was signi cantly rescued by treatment with 1,25(OH) 2 D 3 (1.25) or ED71 (ED), both active vitamin D analogues, with signi cant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which activates osteoblastic activities and is critical for bone remodeling, were signi cantly lower in FR versus control male mice, but restored by administration of either of vitamin D analogue. However, administration of recombinant IGF-I did not rescue reduced bone mass in FR male mice, and administration of either active vitamin D analogue could increase bone mass even in IGF-I conditional knockout FR male mice. Taken together, conditions comparable to the female athlete triad are also a risk for male stress injuries, 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.

Impact of Long-Term Swimming Exercise on Rat Femur Bone Quality

“…These results suggest a possible effect of swimming on inadequate energy availability due to the high energy expenditure resulting from the daily swimming exercise protocol, which could have hindered the animals' growth. There is broad evidence in the literature that low energy availability is associated with compromised bone growth, unbalanced bone remodelling, lower bone mass, and deteriorated geometry and microarchitecture in rodents [53,54]. Nevertheless, bone marrow adiposity, which has also been increased in conditions associated with energy deficiency [55], remained unaffected by swimming.…”