Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis

Abstract

SUMMARY Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears(Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation(P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (P<0.004)post-hibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (P<0.0001) during hibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E2 (PGE2)release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE2 release showed trends similar to the seasonal changes in serum IGF-I. Since both PGE2 and IGF-I are associated with collagenous bone formation, it is possible that seasonal changes in a circulating factor influence IGF-I levels in vivo in bears and PGE2 release in osteoblastic cells in vitro. The significant decrease in serum leptin following arousal from hibernation may promote bone formation during remobilization, assuming there is a similar decrease in intracerebroventricular leptin. These findings support the idea that seasonal changes in the concentration of circulating molecules help regulate bone formation activity and may be important for preventing disuse osteoporosis in bears.

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

“…Serum markers of bone turnover suggest that bone remodeling is increased, but balanced, in black bears during hibernation [26], which is in contrast to the decreased cortical bone remodeling observed in the current study. Both serum carboxy-terminal telopeptide of type-I collagen (ICTP, a bone resorption marker) and serum osteocalcin (a bone formation marker) are elevated in hibernating bears [26].…”

“…Both serum carboxy-terminal telopeptide of type-I collagen (ICTP, a bone resorption marker) and serum osteocalcin (a bone formation marker) are elevated in hibernating bears [26]. At present, this discrepancy cannot be resolved.…”

“…The mechanism by which bears prevent bone loss during hibernation is unknown, but previous work suggests the involvement of parathyroid hormone (PTH) [26]. PTH is the primary regulator of blood calcium levels, and therefore likely plays a major role in maintaining homeostatic serum calcium levels in bears during hibernation.…”

“…PTH is the primary regulator of blood calcium levels, and therefore likely plays a major role in maintaining homeostatic serum calcium levels in bears during hibernation. Serum levels of osteocalcin (a marker of bone formation) and PTH are elevated and positively correlated in hibernating bears [26]. However, previous measurements of PTH levels in bears were made with an assay that detects both intact (PTH 1-84) and large C-terminal fragments of the hormone (C-PTH).…”

“…These findings suggest that bears have evolved a unique biological mechanism to mitigate disuse-induced bone loss. Bears may prevent bone loss during hibernation by maintaining balanced bone remodeling [24,26].…”