Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression

Abstract

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals’ intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression.

The Effects of Caloric Restriction and/or Intermittent Fasting on Bone Health

“…This is consistent with the work of Shien et al, who subjected obese rats to 35% caloric restriction for four months, resulting in decreased bone mineral density and lower leptin and IGF-1 along with changes in several other serum markers 21 . It is important to note that these findings differ somewhat from those observed in rats subjected to 30% caloric restriction from three weeks of age to seven weeks of age, which resulted in similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control 22 . That said, two studies in adult rats subjected to 30% or 40% caloric restriction indicates that the β-adrenoreceptor signaling plays a role in the response to energy restriction, with β-adrenergic blockade attenuating bone loss and preserving serum leptin levels following prolonged calorie restriction 23,24 .…”

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo

“…At the time of testing, femurs were individually positioned on the loading fixture anterior side down and loaded first in the anterior–posterior plane, and then loaded to failure at a rate of 0.05 mm/s, during which displacement and force were collected (100 Hz). Bending moments were calculated from the force (F) data (M = FL/4; N mm), as previously described (Joshi et al, ). Displacement data were divided by L 2 /12 (mm/mm 2 ), where L was the distance between the lower supports.…”

Bioinformatic identification of connective tissue growth factor as an osteogenic protein within skeletal muscle

“…Recently, CR was observed to increase serum osteocalcin in rats, correlating to increased trabecular bone volume in the lumbar spine compared to control (Joshi et al. ). Additionally, CR promoted increased bone functional properties, including lager bone area, cortical area, and moment of inertia (Butler et al.…”